@article {pmid39798621, year = {2025}, author = {Heckmann, ND and Culler, M and Mont, MA and Lieberman, JR and Parvizi, J}, title = {Emerging Concepts in Periprosthetic Joint Infection Research: The Human Microbiome.}, journal = {The Journal of arthroplasty}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.arth.2025.01.001}, pmid = {39798621}, issn = {1532-8406}, abstract = {Microorganisms, including bacteria, fungi, and viruses, that reside on and within the human body are collectively known as the human microbiome. Dysbiosis, or disruption in the microbiome, has been implicated in several disease processes, including asthma, obesity, autoimmune diseases, and numerous other conditions. While the Human Microbiome Project (HMP) and the generation of descriptive studies it inspired established correlations between characteristic patterns in the composition of the microbiome and specific disease phenotypes, current research has begun to focus on elucidating the causal role of the microbiome in disease pathogenesis. Within the field of orthopaedic surgery, researchers have proposed the concept of a "gut-joint axis" by which the intestinal microbiome influences joint health and the development of diseases such as osteoarthritis and periprosthetic joint infection (PJI). It is theorized that intestinal dysbiosis increases gut permeability, leading to the translocation of bacteria and their metabolic products into the systemic circulation and the stimulation of proinflammatory response cascades throughout the body, including within the joints. While correlative studies have identified patterns of dysbiotic derangement associated with osteoarthritis and PJI, translational research is needed to clarify the precise mechanisms by which these changes influence disease processes. Additionally, an emerging body of literature has challenged the previously held belief that certain body sites are sterile and do not possess a microbiome, with studies identifying distinct microbial genomic signatures and a core microbiome that varies between anatomic sites. A more thorough characterization of the joint microbiome may have profound implications for our understanding of PJI pathogenesis and our ability to stratify patients based on risk. The purpose of this review was to outline our current understanding of the human microbiome, to describe the gut-joint axis and its role in specific pathologies, including PJI, and to highlight the potential of microbiome-based therapeutic interventions in the field of orthopaedics.}, }
@article {pmid39794490, year = {2025}, author = {Dilmore, AH and Kuplicki, R and McDonald, D and Kumar, M and Estaki, M and Youngblut, N and Tyakht, A and Ackermann, G and Blach, C and MahmoudianDehkordi, S and Dunlop, BW and Bhattacharyya, S and Guinjoan, S and Mandaviya, P and Ley, RE and Kaddaruh-Dauok, R and Paulus, MP and Knight, R and , }, title = {Medication use is associated with distinct microbial features in anxiety and depression.}, journal = {Molecular psychiatry}, volume = {}, number = {}, pages = {}, pmid = {39794490}, issn = {1476-5578}, support = {U19AG063744//U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ ; 5U19AG063744//U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ ; 5U19AG063744//U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ ; 5U19AG063744//U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ ; 5U19AG063744//U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ ; 5U19AG063744//U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ ; }, abstract = {This study investigated the relationship between gut microbiota and neuropsychiatric disorders (NPDs), specifically anxiety disorder (ANXD) and/or major depressive disorder (MDD), as defined by Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV or V criteria. The study also examined the influence of medication use, particularly antidepressants and/or anxiolytics, classified through the Anatomical Therapeutic Chemical (ATC) Classification System, on the gut microbiota. Both 16S rRNA gene amplicon sequencing (16S) and shallow shotgun sequencing (WGS) were performed on DNA extracted from 666 fecal samples from the Tulsa-1000 and Neurocomputational Mechanisms of Affiliation and Personality Study Center for Biomedical Research Excellence (NeuroMAP CoBRE) cohorts. The results highlight the significant influence of medication use; antidepressant use is associated with significant differences in gut microbiota beta diversity and has a larger effect size than NPD diagnosis. Next, specific microbes were associated with ANXD and MDD, highlighting their potential for non-pharmacological intervention. Finally, the study demonstrated the capability of Random Forest classifiers to predict diagnoses of NPD and medication use from microbial profiles, suggesting a promising direction for the use of gut microbiota as biomarkers for NPD. Though the effect sizes were larger in females than males, similar trends emerged for both sexes. These findings encourage future research on the gut microbiota's role in NPD and its interactions with pharmacological treatments.}, }
@article {pmid39754287, year = {2025}, author = {Epstein, HE and Brown, T and Akinrinade, AO and McMinds, R and Pollock, FJ and Sonett, D and Smith, S and Bourne, DG and Carpenter, CS and Knight, R and Willis, BL and Medina, M and Lamb, JB and Thurber, RV and Zaneveld, JR}, title = {Evidence for microbially-mediated tradeoffs between growth and defense throughout coral evolution.}, journal = {Animal microbiome}, volume = {7}, number = {1}, pages = {1}, pmid = {39754287}, issn = {2524-4671}, support = {2006244//National Science Foundation/ ; 1442306//National Science Foundation/ ; 1942647//National Science Foundation/ ; }, abstract = {BACKGROUND: Evolutionary tradeoffs between life-history strategies are important in animal evolution. Because microbes can influence multiple aspects of host physiology, including growth rate and susceptibility to disease or stress, changes in animal-microbial symbioses have the potential to mediate life-history tradeoffs. Scleractinian corals provide a biodiverse, data-rich, and ecologically-relevant host system to explore this idea.<br><br>RESULTS: Using a comparative approach, we tested if coral microbiomes correlate with disease susceptibility across 425&#xa0;million years of coral evolution by conducting a cross-species coral microbiome survey (the "Global Coral Microbiome Project") and combining the results with long-term global disease prevalence and coral trait data. Interpreting these data in their phylogenetic context, we show that microbial dominance predicts disease susceptibility, and traced this dominance-disease association to a single putatively beneficial symbiont genus, Endozoicomonas. Endozoicomonas relative abundance in coral tissue explained 30% of variation in disease susceptibility and 60% of variation in microbiome dominance across 40 coral genera, while also correlating strongly with high growth rates.<br><br>CONCLUSIONS: These results demonstrate that the evolution of Endozoicomonas symbiosis in corals correlates with both disease prevalence and growth rate, and suggest a mediating role. Exploration of the mechanistic basis for these findings will be important for our understanding of how microbial symbioses influence animal life-history tradeoffs.}, }
@article {pmid39732755, year = {2024}, author = {Bao, Z and Yang, Z and Sun, R and Chen, G and Meng, R and Wu, W and Li, MD}, title = {Predicting host health status through an integrated machine learning framework: insights from healthy gut microbiome aging trajectory.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {31143}, pmid = {39732755}, issn = {2045-2322}, support = {2016YFC0906300//China Precision Medicine Initiative/ ; 2016YFC0906300//China Precision Medicine Initiative/ ; 2016YFC0906300//China Precision Medicine Initiative/ ; 2016YFC0906300//China Precision Medicine Initiative/ ; 2016YFC0906300//China Precision Medicine Initiative/ ; 2016YFC0906300//China Precision Medicine Initiative/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; *Machine Learning ; *Health Status ; *Aging ; Female ; Male ; Middle Aged ; Aged ; Cohort Studies ; Adult ; }, abstract = {The gut microbiome, recognized as a critical component in the development of chronic diseases and aging processes, constitutes a promising approach for predicting host health status. Previous research has underscored the potential of microbiome-based predictions, and the rapid advancements of machine learning techniques have introduced new opportunities for exploiting microbiome data. To predict various host nonhealthy conditions, this study proposed an integrated machine learning-based estimation pipeline of Gut Age Index (GAI) by establishing a health aging baseline with the gut microbiome data from healthy individuals. We assessed the performance of GAI pipeline on two extensive cohorts - the Guangdong Gut Microbiome Project (GGMP) and the American Gut Project (AGP). In the GGMP cohort, for 20 common chronic diseases such as metabolic syndrome, obesity, and cardiovascular diseases, the proposed GAI achieved a balanced accuracy, ranging from 66 to 75%, with the prediction performance for atherosclerosis being the highest. In the AGP cohort, the balanced accuracy of GAI ranged from 58 to 72% for 10 diseases. Based on the results from these two datasets, we conclude that our proposed approach in this study can be used to predict individual health status, which offers the potential for scalable, cost-effective, and personalized health insights.}, }
@article {pmid39684937, year = {2024}, author = {Balla, B and Illés, A and Tobiás, B and Pikó, H and Beke, A and Sipos, M and Lakatos, P and Kósa, JP}, title = {The Role of the Vaginal and Endometrial Microbiomes in Infertility and Their Impact on Pregnancy Outcomes in Light of Recent Literature.}, journal = {International journal of molecular sciences}, volume = {25}, number = {23}, pages = {}, pmid = {39684937}, issn = {1422-0067}, support = {2020-4.1.1.-TKP2020-MOLORKIV//Hungarian Ministry of Innovation and Technology/ ; }, mesh = {Humans ; Female ; *Vagina/microbiology ; Pregnancy ; *Microbiota ; *Endometrium/microbiology/metabolism ; *Pregnancy Outcome ; Dysbiosis/microbiology ; Infertility, Female/microbiology ; Infertility/microbiology ; }, abstract = {The Human Microbiome Project (HMP), initiated in 2007, aimed to gather comprehensive knowledge to create a genetic and metabolic map of human-associated microorganisms and their contribution to physiological states and predisposition to certain diseases. Research has revealed that the human microbiome is highly diverse and exhibits significant interpersonal variability; consequently, its exact impact on health remains unclear. With the development of next-generation sequencing (NGS) technologies, the broad spectrum of microbial communities has been better characterized. The lower female genital tract, particularly the vagina, is colonized by various bacterial species, with Lactobacillus spp. predominating. The upper female genital tract, especially the uterus, was long considered sterile. However, recent studies have identified a distinct endometrial microbiome. A Lactobacillus-dominated microbiome of the female genital tract is associated with favorable reproductive outcomes, including higher success rates in natural conception and assisted reproductive technologies (ART). Conversely, microbial imbalances, or dysbiosis, marked by reduced Lactobacilli as well as an increased diversity and abundance of pathogenic species (e.g., Gardnerella vaginalis or Prevotella spp.), are linked to infertility, implantation failure, and pregnancy complications such as miscarriage and preterm birth. Dysbiosis can impair the vaginal or endometrial mucosal barrier and also trigger pro-inflammatory responses, disrupting essential reproductive processes like implantation. Despite growing evidence supporting the associations between the microbiome of the female genital tract and certain gynecological and obstetric conditions, clear microbial biomarkers have yet to be identified, and there is no consensus on the precise composition of a normal or healthy microbiome. The lack of standardized protocols and biomarkers limits the routine use of microbiome screening tests. Therefore, larger patient cohorts are needed to facilitate comparative studies and improve our understanding of the physiological microbiome profiles of the uterus and vagina, as well as how dysbiosis may influence clinical outcomes. Further research is required to refine diagnostic tools and develop personalized therapeutic strategies to improve fertility and pregnancy outcomes.}, }
@article {pmid39662756, year = {2024}, author = {Hodgkiss, R and Acharjee, A}, title = {Unravelling metabolite-microbiome interactions in inflammatory bowel disease through AI and interaction-based modelling.}, journal = {Biochimica et biophysica acta. Molecular basis of disease}, volume = {1871}, number = {3}, pages = {167618}, doi = {10.1016/j.bbadis.2024.167618}, pmid = {39662756}, issn = {1879-260X}, abstract = {Inflammatory Bowel Diseases (IBDs) are chronic inflammatory disorders of the gastrointestinal tract and colon affecting approximately 7 million individuals worldwide. The knowledge of specific pathology and aetiological mechanisms leading to IBD is limited, however a reduced immune system, antibiotic use and reserved diet may initiate symptoms. Dysbiosis of the gut microbiome, and consequently a varied composition of the metabolome, has been extensively linked to these risk factors and IBD. Metagenomic sequencing and liquid-chromatography mass spectrometry (LC-MS) of N = 220 fecal samples by Fransoza et al., provided abundance data on microbial genera and metabolites for use in this study. Identification of differentially abundant microbes and metabolites was performed using a Wilcoxon test, followed by feature selection of random forest (RF), gradient-boosting (XGBoost) and least absolute shrinkage operator (LASSO) models. The performance of these features was then validated using RF models on the Human Microbiome Project 2 (HMP2) dataset and a microbial community (MICOM) model was utilised to predict and interpret the interactions between key microbes and metabolites. The Flavronifractor genus and microbes of the families Lachnospiraceae and Oscillospiraceae were found differential by all models. Metabolic pathways commonly influenced by such microbes in IBD were CoA biosynthesis, bile acid metabolism and amino acid production and degradation. This study highlights distinct interactive microbiome and metabolome profiles within IBD and the highly potential pathways causing disease pathology. It therefore paves way for future investigation into new therapeutic targets and non-invasive diagnostic tools for IBD.}, }
@article {pmid39660282, year = {2024}, author = {Bai, B and Luo, L and Yao, F and Sun, Q and Chen, X and Zheng, W and Jiang, L and Wang, X and Su, G}, title = {The causal relationship between the human gut microbiota and pyogenic arthritis: a Mendelian randomization study.}, journal = {Frontiers in cellular and infection microbiology}, volume = {14}, number = {}, pages = {1452480}, pmid = {39660282}, issn = {2235-2988}, mesh = {Humans ; *Mendelian Randomization Analysis ; *Gastrointestinal Microbiome/genetics ; *Arthritis, Infectious/microbiology/genetics ; *Genome-Wide Association Study ; Bacteria/genetics/classification/isolation &amp; purification ; }, abstract = {BACKGROUND: Recent studies have indicated the role of the gut microbiota in the progression of osteoarticular diseases, however, the causal relationship between the gut microbiota and pyogenic arthritis remains unclear. There is also a lack of theoretical basis for the application of the gut microbiota in the treatment of pyogenic arthritis.<br><br>METHODS: In our study, we utilized the largest genome-wide association study (GWAS) data from the MiBioGen Consortium involving 13,400 participants and extracted summary statistical data of the microbiota metabolic pathways of 7,738 participants of European descent from the Dutch Microbiome Project (DMP) The data of pyogenic arthritis were derived from the FinnGen R10 database, including 1,086 patients and 147,221 controls. We employed the two-sample Mendelian randomization approach to investigate the causal association between the gut microbiota and pyogenic arthritis. Our methods comprised inverse variance weighting, Mendelian Randomization Egger regression, weighted median, and weighted modal methods. Subsequently, polygenic and heterogeneity analyses were conducted.<br><br>RESULTS: At the class level, &#x3b2;-proteobacteria is positively correlated with the risk of pyogenic arthritis. At the order level, Burkholderia is positively associated with the disease. At the genus level, the unclassified genus of Sutterellaceae is positively correlated with the disease, while the unnamed genus of Lachnospiraceae, Rothia, and the unnamed genus of Erysipelotrichaceae are negatively correlated with the disease. In addition, Faecalibacterium and Finegoldia are also negatively correlated with the disease. Sensitivity analysis did not show any abnormal evidence.<br><br>CONCLUSION: This study indicates that &#x3b2;-proteobacteria, Burkholderiales, and the unclassified genus of Sutterellaceae are associated with an increased risk of the disease, while the unnamed genus of Lachnospiraceae, Rothia, the unnamed genus of Erysipelotrichaceae, Faecalibacterium, and Finegoldia are related to a reduced risk. Future studies are needed to elucidate the specific mechanisms by which these specific bacterial groups affect pyogenic arthritis.}, }
@article {pmid39639265, year = {2024}, author = {Ma, ZS}, title = {Revisiting microgenderome: detecting and cataloguing sexually unique and enriched species in human microbiomes.}, journal = {BMC biology}, volume = {22}, number = {1}, pages = {284}, pmid = {39639265}, issn = {1741-7007}, mesh = {Humans ; Female ; Male ; *Microbiota ; *Sex Characteristics ; Species Specificity ; }, abstract = {BACKGROUND: Microgenderome or arguably more accurately microsexome refers to studies on sexual dimorphism of human microbiomes aimed at investigating bidirectional interactions between human microbiomes, sex hormones, and immune systems. It is important because of its implications to disease susceptibility and therapy, in which men and women demonstrate divergence in many diseases especially autoimmune diseases. In a previous report [1], we presented analyses of several key ecological aspects of microgenderome by leveraging the large datasets of the HMP (human microbiome project) but failed to offer species-level composition differences such as sexually unique species (US) and enriched species (ES). Existing approaches, for such tasks, including differential species relative abundance analysis and differential network analysis, possess certain limitations given that virtually all rely on species abundance alone or are univariate, while ignoring species distribution information across samples. Obviously, it is both species abundance and distribution that shape/drive the structure and dynamics of human microbiomes, and both should be equally responsible for the universal heterogeneity of microbiomes including the sexual dimorphism.<br><br>RESULTS: Here, we fill the gap by taking advantages of a recently developed computational algorithm, species specificity, and specificity diversity (SSD) framework (refer to the companion article) to reanalyze the HMP and complementary seminovaginal microbiome datasets. The SSD framework can randomly search and catalogue the sexually specific unique/enriched species with statistical rigor, guided by species specificity (a synthetic metric of abundance and distribution) and specificity diversity (SD). The SSD framework reveals that men seem to have more unique species than women in their gut and reproductive system microbiomes, but women seem to have more unique species than men in the airway, oral, and skin microbiomes, which is likely due to sexual dimorphism in the hormone and immune systems. We further investigate co-dependency and heterogeneity of those sexually unique/enriched species across 15 body sites, with core/periphery network analyses.<br><br>CONCLUSIONS: This study not only produced sexually unique/enriched species in the human microbiomes and analyzed their codependency and heterogeneity but also further validated the robustness of the SSD framework presented in the companion article, by performing all negative control tests based on the HMP gut microbiome samples.}, }
@article {pmid39612063, year = {2024}, author = {Xu, H and Li, O and Kim, D and Bao, Z and Yang, F}, title = {Gut microbiota and epigenetic age acceleration: a bi-directional Mendelian randomization study.}, journal = {Aging clinical and experimental research}, volume = {36}, number = {1}, pages = {227}, pmid = {39612063}, issn = {1720-8319}, support = {82071581//National Natural Science Foundation of China/ ; XXRC2211//Huadong Hospital Program/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome/genetics ; *Mendelian Randomization Analysis ; *Aging/genetics ; *Epigenesis, Genetic ; Genome-Wide Association Study ; }, abstract = {BACKGROUND: The gut microbiota is closely related to aging, but the genetic relationship between gut microbiota and aging has not been well investigated. The aim of the study was to explore the association of microbiota with epigenetic age acceleration (EAA) using the Mendelian randomization.<br><br>METHOD: The independent genetic instruments of gut microbiota were obtained from MiBioGen consortium and the Dutch Microbiome Project. EAA data were derived from genome-wide association study. To assess the causal relationship between gut microbiota and EAA, we applied four different methods of Mendelian Randomization (MR) analysis: the inverse variance weighted method (IVW), the MR-Egger regression, the weighted median analysis (WMA), and the weighted mode. Furthermore, sensitivity analyses were conducted to evaluate heterogeneity and horizontal pleiotropy.<br><br>RESULTS: We identified potential causal associations between 12 bacterial taxa and EAA (PIVW and PWMA < 0.05). Among them, species Holdemania_unclassified (OR: 1.31, 95% CI: 1.13-1.52, P&#x2009;=&#x2009;0.0004) retained a strong positive association with GrimAge acceleration. Family Acidaminococcaceae (OR: 0.64, 95% CI: 0.44-0.93, P&#x2009;=&#x2009;0.019) and family Clostridiaceae1 (OR: 0.69, 95% CI: 0.49-0.97 P&#x2009;=&#x2009;0.031) were negative association with GrimAge acceleration. Reverse MR analyses indicated that EAA was associated with 6 bacterial taxa in IVW and WMA. Among them, a strong inverse association was found between Phenoage acceleration and genus Turicibacter (OR: 0.928, 95%CI: 0.888-0.971, PIVW and PWMA < 0.001).<br><br>CONCLUSION: Our study implicates the potential causal effects of specific microbiota on EAA, potentially providing novel insights into the prevention aging through specific gut microbiota.}, }
@article {pmid39563467, year = {2024}, author = {Liu, R and Wang, Y and Cheng, D}, title = {Micro-DeMix: a mixture beta-multinomial model for investigating the heterogeneity of the stool microbiome compositions.}, journal = {Bioinformatics (Oxford, England)}, volume = {40}, number = {12}, pages = {}, pmid = {39563467}, issn = {1367-4811}, support = {DMS-2220523//National Institute of Health/ ; 854127//Simons Foundation Collaboration/ ; }, mesh = {Humans ; *Feces/microbiology ; *Gastrointestinal Microbiome ; *Software ; Inflammatory Bowel Diseases/microbiology ; }, abstract = {MOTIVATION: Extensive research has uncovered the critical role of the human gut microbiome in various aspects of health, including metabolism, nutrition, physiology, and immune function. Fecal microbiota is often used as a proxy for understanding the gut microbiome, but it represents an aggregate view, overlooking spatial variations across different gastrointestinal (GI) locations. Emerging studies with spatial microbiome data collected from specific GI regions offer a unique opportunity to better understand the spatial composition of the stool microbiome.<br><br>RESULTS: We introduce Micro-DeMix, a mixture beta-multinomial model that deconvolutes the fecal microbiome at the compositional level by integrating stool samples with spatial microbiome data. Micro-DeMix facilitates the comparison of microbial compositions across different GI regions within the stool microbiome through a hypothesis-testing framework. We demonstrate the effectiveness and efficiency of Micro-DeMix using multiple simulated datasets and the inflammatory bowel disease data from the NIH Integrative Human Microbiome Project.<br><br>The R package is available at https://github.com/liuruoqian/MicroDemix.}, }
@article {pmid39559896, year = {2024}, author = {Zhao, Q and Baranova, A and Cao, H and Zhang, F}, title = {Evaluating Causal Effects of Gut Microbiome on Alzheimer's Disease.}, journal = {The journal of prevention of Alzheimer's disease}, volume = {11}, number = {6}, pages = {1843-1848}, doi = {10.14283/jpad.2024.113}, pmid = {39559896}, issn = {2426-0266}, mesh = {*Alzheimer Disease/microbiology ; *Gastrointestinal Microbiome ; Humans ; *Genome-Wide Association Study ; Mendelian Randomization Analysis ; }, abstract = {BACKGROUND: The preceding evidence indicates a close correlation between imbalances in the gut microbiome and Alzheimer's disease (AD), yet the direct causal relationship remains unclear. Our objective is to investigate this potential causal connection.<br><br>METHODS: We obtained summary results from two significant genome-wide association studies (GWAS) on gut microbiota (the MibioGen consortium and the Dutch Microbiome Project), along with one GWAS summary result for AD. Using a two-sample Mendelian randomization (TSMR) analysis, we examined the potential causal effects of gut microbiota on AD.<br><br>RESULTS: Our TSMR analysis revealed that 16 gut bacterial taxa were linked to a reduced risk of AD. These included phylum Tenericutes, classes Bacilli and Clostridia along with its order Clostridiales, family Bacteroidaceae, genus Bacteroides, and species Bifidobacterium bifidum (OR: 0.867~0.971, P &#x2264; 0.045). Conversely, the presence of 12 taxa correlated with an increased risk of AD. These comprised class Actinobacteria and its family Coriobacteriaceae, as well as class Betaproteobacteria, its order Burkholderiales, and its family Sutterellaceae (OR: 1.042~1.140, P &#x2264; 0.035).<br><br>CONCLUSION: Our research uncovered evidence suggesting certain gut bacterial species might play a causal role in AD risk, providing a fresh angle for AD treatment strategies.}, }
@article {pmid39548551, year = {2024}, author = {Chen, S and Chen, W and Wang, X and Liu, S}, title = {Mendelian randomization analyses support causal relationships between gut microbiome and longevity.}, journal = {Journal of translational medicine}, volume = {22}, number = {1}, pages = {1032}, pmid = {39548551}, issn = {1479-5876}, support = {32100039//National Natural Science Foundation of China/ ; }, mesh = {*Longevity ; Humans ; *Mendelian Randomization Analysis ; *Gastrointestinal Microbiome/genetics ; *Genome-Wide Association Study ; Causality ; }, abstract = {BACKGROUND: Gut microbiome plays a significant role in longevity, and dysbiosis is indeed one of the hallmarks of aging. However, the causal relationship between gut microbiota and human longevity or aging remains elusive.<br><br>METHODS: Our study assessed the causal relationships between gut microbiome and longevity using Mendelian Randomization (MR). Summary statistics for the gut microbiome were obtained from four genome-wide association study (GWAS) meta-analysis of the MiBioGen consortium (N&#x2009;=&#x2009;18,340), Dutch Microbiome Project (N&#x2009;=&#x2009;7738), German individuals (N&#x2009;=&#x2009;8956), and Finland individuals (N&#x2009;=&#x2009;5959). Summary statistics for Longevity were obtained from Five GWAS meta-analysis, including Human healthspan (N&#x2009;=&#x2009;300,447), Longevity (N&#x2009;=&#x2009;36,745), Lifespans (N&#x2009;=&#x2009;1,012,240), Parental longevity (N&#x2009;=&#x2009;389,166), and Frailty (one of the primary aging-linked physiological hallmarks, N&#x2009;=&#x2009;175,226).<br><br>RESULTS: Our findings reveal several noteworthy associations, including a negative correlation between Bacteroides massiliensis and longevity, whereas the genus Subdoligranulum and Alistipes, as well as species Alistipes senegalensis and Alistipes shahii, exhibited positive associations with specific longevity traits. Moreover, the microbial pathway of coenzyme A biosynthesis I, pyruvate fermentation to acetate and lactate II, and pentose phosphate pathway exhibited positive associations with two or more traits linked to longevity. Conversely, the TCA cycle VIII (helicobacter) pathway consistently demonstrated a negative correlation with lifespan and parental longevity.<br><br>CONCLUSIONS: Our findings of this MR study indicated many significant associations between gut microbiome and longevity. These microbial taxa and pathways may potentially play a protective role in promoting longevity or have a suppressive effect on lifespan.}, }
@article {pmid39468693, year = {2024}, author = {Tian, Y and Gu, M and Chen, D and Dong, Q and Wang, Y and Sun, W and Kong, X}, title = {Causal Associations Between the Gut Microbiota and Hypertension-Related Traits Through Mendelian Randomization: A Cross-Sectional Cohort Study.}, journal = {Journal of clinical hypertension (Greenwich, Conn.)}, volume = {}, number = {}, pages = {}, doi = {10.1111/jch.14925}, pmid = {39468693}, issn = {1751-7176}, support = {//Jiangsu Province Hospital High-level Talent Cultivation Program (Phase I)/ ; }, abstract = {Previous studies have suggested a link between the gut microbiome and hypertension-related traits like blood pressure. However, these reports are often limited by weak causal evidence. This study investigates the potential causal association between gut microbiota and hypertension-related traits using Mendelian randomization with summary data from genome-wide association studies. The inverse-variance weighted method revealed that the Clostridium innocuum group (Odds ratio [OR]: 1.0047, 95% confidence interval [CI]: 1.0004-1.0090, p = 0.0336), Eubacterium fissicatena group (OR: 1.0047, 95% CI: 1.0005-1.0088, p = 0.0266), Lachnospiraceae FCS020 group (OR: 1.0063, 95% CI: 1.0004-1.0122, p = 0.0361), and Olsenella (OR: 1.0044, 95% CI: 1.0001-1.0088, p = 0.0430) were associated with an increased risk of hypertension. Conversely, Flavonifractor (OR: 0.9901, 95% CI: 0.9821-0.9982, p = 0.0166), Parabacteroides (OR: 0.9874, 95% CI: 0.9776-0.9972, p = 0.0121), and Senegalimassilia (OR: 0.9907, 95% CI: 0.9842-0.9974, p = 0.0063) were associated with a decreased risk of hypertension. External validation with the Guangdong Gut Microbiome Project confirmed a negative correlation between Parabacteroides and hypertension, potentially through metabolic pathways. These findings provide further evidence supporting the hypothesis that microbes and their metabolites play a role in blood pressure regulation.}, }
@article {pmid39394961, year = {2024}, author = {Branck, T and Hu, Z and Nickols, WA and Walsh, AM and Bhosle, A and Short, MI and Nearing, JT and Asnicar, F and McIver, LJ and Maharjan, S and Rahnavard, A and Louyakis, AS and Badri, DV and Brockel, C and Thompson, KN and Huttenhower, C}, title = {Comprehensive profile of the companion animal gut microbiome integrating reference-based and reference-free methods.}, journal = {The ISME journal}, volume = {18}, number = {1}, pages = {}, pmid = {39394961}, issn = {1751-7370}, mesh = {Animals ; *Gastrointestinal Microbiome/genetics ; Dogs/microbiology ; Cats ; *Pets/microbiology ; *Feces/microbiology ; *Phylogeny ; *Metagenome ; Humans ; *Metagenomics ; Bacteria/genetics/classification/isolation &amp; purification ; }, abstract = {The gut microbiome of companion animals is relatively underexplored, despite its relevance to animal health, pet owner health, and basic microbial community biology. Here, we provide the most comprehensive analysis of the canine and feline gut microbiomes to date, incorporating 2639 stool shotgun metagenomes (2272 dog and 367 cat) spanning 14 publicly available datasets (n = 730) and 8 new study populations (n = 1909). These are compared with 238 and 112 baseline human gut metagenomes from the Human Microbiome Project 1-II and a traditionally living Malagasy cohort, respectively, processed in a manner identical to the animal metagenomes. All microbiomes were characterized using reference-based taxonomic and functional profiling, as well as de novo assembly yielding metagenomic assembled genomes clustered into species-level genome bins. Companion animals shared 184 species-level genome bins not found in humans, whereas 198 were found in all three hosts. We applied novel methodology to distinguish strains of these shared organisms either transferred or unique to host species, with phylogenetic patterns suggesting host-specific adaptation of microbial lineages. This corresponded with functional divergence of these lineages by host (e.g. differences in metabolic and antibiotic resistance genes) likely important to companion animal health. This study provides the largest resource to date of companion animal gut metagenomes and greatly contributes to our understanding of the "One Health" concept of a shared microbial environment among humans and companion animals, affecting infectious diseases, immune response, and specific genetic elements.}, }
@article {pmid39377919, year = {2024}, author = {Tiwari, P and Ansari, WA and Kumar, SC and Tiwari, PK and Kumar, M and Chakdar, H and Srivastava, AK and Saxena, AK and Shantikumar, L}, title = {Genetic Diversity and Functional Potential of Streptomyces spp. Isolated from Pachmarhi Biosphere Reserve, India.}, journal = {Current microbiology}, volume = {81}, number = {11}, pages = {397}, pmid = {39377919}, issn = {1432-0991}, support = {Indian Soil Microbiome Project//National Bureau of Agriculturally Important Microorganisms/ ; }, mesh = {*Streptomyces/genetics/isolation &amp; purification/classification ; India ; *Phylogeny ; *RNA, Ribosomal, 16S/genetics ; *Genetic Variation ; Soil Microbiology ; DNA, Bacterial/genetics ; }, abstract = {Streptomyces is a diverse genus, well known for producing a wide array of metabolites that have significant industrial utilization. The present study investigates the genetic and functional diversity of Streptomyces spp. isolated from the Pachmarhi Biosphere Reserve (PBR), India, an unexplored site. The 16S rRNA gene sequencing and analysis revealed 96 isolates belonging to 40 different species indicating a substantial phylogenetic diversity. The strains were clustered into two groups: a major cluster with 94 strains and a small cluster with two strains. BOX- PCR analyses revealed an incredible genetic diversity existing among the strains of Streptomyces spp. in PBR. The analyses revealed the intra-species diversity and inter-species closeness within the genus Streptomyces in the study area. Qualitative screening for enzyme production has shown that 53, 42, 41, 11, and 54 strains tested positive for CMCase, xylanase, amylase, pectinase, and β-glucosidase, respectively. Additionally, 54 strains tested positive for PHB production. The strains were assayed quantitatively for the production of CMCase, xylanase, amylase, and pectinase. Streptomyces sp. MP9-2, Streptomyces sp. MP10-11, Streptomyces sp. MP10-18, and Streptomyces sp. MP10-6 recorded maximum CMCase (0.604 U/mL), xylanase (0.553 U/mL), amylase (1.714 U/mL), and pectinase (13.15 U/mL) activities, respectively. Furthermore, several strains demonstrated plant growth-promoting traits, viz. zinc and phosphate solubilization and production of ammonia, HCN (hydrogen cyanide), and IAA (Indole acetic acid), and nitrogen fixation. Fifty strains showed antifungal activity against Fusarium oxysporum f. sp. lycopersici with inhibitions ranging from 7.5 to 47.5%. Current findings underscore the ecological and biotechnological significance of Streptomyces spp. in the unexplored habitat of PBR.}, }
@article {pmid39349378, year = {2024}, author = {Palmer, D and Henze, L and Murua Escobar, H and Walter, U and Kowald, A and Fuellen, G}, title = {Multicohort study testing the generalisability of the SASKit-ML stroke and PDAC prognostic model pipeline to other chronic diseases.}, journal = {BMJ open}, volume = {14}, number = {9}, pages = {e088181}, pmid = {39349378}, issn = {2044-6055}, mesh = {Humans ; *Diabetes Mellitus, Type 2/complications ; Prognosis ; Female ; Male ; *Pancreatic Neoplasms ; *Stroke ; Middle Aged ; Arthritis, Rheumatoid ; Machine Learning ; Inflammatory Bowel Diseases ; Aged ; Longitudinal Studies ; Chronic Disease ; Prospective Studies ; Biomarkers/blood ; Cohort Studies ; }, abstract = {OBJECTIVES: To validate and test the generalisability of the SASKit-ML pipeline, a prepublished feature selection and machine learning pipeline for the prediction of health deterioration after a stroke or pancreatic adenocarcinoma event, by using it to identify biomarkers of health deterioration in chronic disease.<br><br>DESIGN: This is a validation study using a predefined protocol applied to multiple publicly available datasets, including longitudinal data from cohorts with type 2 diabetes (T2D), inflammatory bowel disease (IBD), rheumatoid arthritis (RA) and various cancers. The datasets were chosen to mimic as closely as possible the SASKit cohort, a prospective, longitudinal cohort study.<br><br>DATA SOURCES: Public data were used from the T2D (77 patients with potential pre-diabetes and 18 controls) and IBD (49 patients with IBD and 12 controls) branches of the Human Microbiome Project (HMP), RA Map (RA-MAP, 92 patients with RA, 22 controls) and The Cancer Genome Atlas (TCGA, 16 cancers).<br><br>METHODS: Data integration steps were performed in accordance with the prepublished study protocol, generating features to predict disease outcomes using 10-fold cross-validated random survival forests.<br><br>OUTCOME MEASURES: Health deterioration was assessed using disease-specific clinical markers and endpoints across different cohorts. In the HMP-T2D cohort, the worsening of glycated haemoglobin (HbA1c) levels (5.7% or more HbA1c in the blood), fasting plasma glucose (at least 100&#x2009;mg/dL) and oral glucose tolerance test (at least 140) results were considered. For the HMP-IBD cohort, a worsening by at least 3 points of a disease-specific severity measure, the "Simple Clinical Colitis Activity Index" or "Harvey-Bradshaw Index" indicated an event. For the RA-MAP cohort, the outcome was defined as the worsening of the "Disease Activity Score 28" or "Simple Disease Activity Index" by at least five points, or the worsening of the "Health Assessment Questionnaire" score or an increase in the number of swollen/tender joints were evaluated. Finally, the outcome for all TCGA datasets was the progression-free interval.<br><br>RESULTS: Models for the prediction of health deterioration in T2D, IBD, RA and 16 cancers were produced. The T2D (C-index of 0.633 and Integrated Brier Score (IBS) of 0.107) and the RA (C-index of 0.654 and IBS of 0.150) models were modestly predictive. The IBD model was uninformative. TCGA models tended towards modest predictive power.<br><br>CONCLUSIONS: The SASKit-ML pipeline produces informative and useful features with the power to predict health deterioration in a variety of diseases and cancers; however, this performance is disease-dependent.}, }
@article {pmid39309525, year = {2024}, author = {Liu, L and He, G and Yu, R and Lin, B and Lin, L and Wei, R and Zhu, Z and Xu, Y}, title = {Causal relationships between gut microbiome and obstructive sleep apnea: a bi-directional Mendelian randomization.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1410624}, pmid = {39309525}, issn = {1664-302X}, abstract = {BACKGROUND: Previous studies have identified a clinical association between gut microbiota and Obstructive sleep apnea (OSA), but the potential causal relationship between the two has not been determined. Therefore, we aim to utilize Mendelian randomization (MR) to investigate the potential causal effects of gut microbiota on OSA and the impact of OSA on altering the composition of gut microbiota.<br><br>METHODS: Bi-directional MR and replicated validation were utilized. Summary-level genetic data of gut microbiota were derived from the MiBioGen consortium and the Dutch Microbiome Project (DMP). Summary statistics of OSA were drawn from FinnGen Consortium and Million Veteran Program (MVP). Inverse-variance-weighted (IVW), weighted median, MR-Egger, Simple Mode, and Weighted Mode methods were used to evaluate the potential causal link between gut microbiota and OSA.<br><br>RESULTS: We identified potential causal associations between 23 gut microbiota and OSA. Among them, genus Eubacterium xylanophilum group (OR&#x2009;=&#x2009;0.86; p&#x2009;=&#x2009;0.00013), Bifidobacterium longum (OR&#x2009;=&#x2009;0.90; p&#x2009;=&#x2009;0.0090), Parabacteroides merdae (OR&#x2009;=&#x2009;0.85; p&#x2009;=&#x2009;0.00016) retained a strong negative association with OSA after the Bonferroni correction. Reverse MR analyses indicated that OSA was associated with 20 gut microbiota, among them, a strong inverse association between OSA and genus Anaerostipes (beta&#x2009;=&#x2009;-0.35; p&#x2009;=&#x2009;0.00032) was identified after Bonferroni correction.<br><br>CONCLUSION: Our study implicates the potential bi-directional causal effects of the gut microbiota on OSA, potentially providing new insights into the prevention and treatment of OSA through specific gut microbiota.}, }
@article {pmid39286351, year = {2024}, author = {Jin, W and Li, B and Wang, L and Zhu, L and Chai, S and Hou, R}, title = {The causal association between gut microbiota and postpartum depression: a two-sample Mendelian randomization study.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1415237}, pmid = {39286351}, issn = {1664-302X}, abstract = {BACKGROUND: An escalating body of clinical trials and observational studies hints at a plausible link between gut flora and postpartum depression (PPD). The definitive causal dynamics between these two entities remain shrouded in ambiguity. Therefore, in this study, we employed the two-sample Mendelian randomization approach to ascertain the causal link between gut microbiota and PPD.<br><br>METHODS: Summary-level GWAS data related to the human gut microbiota were obtained from the international consortium MiBioGen and the Dutch Microbiome Project (species). For PPD, GWAS data were derived from the FinnGen biobank, consisting 57,604 cases and 596,601 controls. The inverse variance weighted method (IVW) as the cornerstone of our analytical approach. Subsequent to this, a comprehensive suite of tests for pleiotropy and heterogeneity were conducted to ensure the reliability and robustness of our findings.<br><br>RESULTS: We identified 12 bacterial taxa associated with the risk of PPD. Veillonellaceae, Ruminococcaceae UCG 011, Bifidobacterium adolescentis, Paraprevotella clara, Clostridium leptum, Eubacterium siraeum, Coprococcus catus exhibited an inversely associated with the risk of PPD. Alphaproteobacteria, Roseburia, FamilyXIIIAD3011group, Alistipes onderdonkii, Bilophila wadsworthia showed a positive correlation with the risk of PPD.<br><br>LIMITATIONS: The GWAS data derived from the MiBioGen consortium, DMP, and FinnGen consortium, may introduce selection bias. Moreover, the data primarily originates from European populations, hence extrapolating these results to diverse populations should be approached with caution. The etiological factors behind PPD remain enigmatic, alluding to the existence of potential undisclosed confounders.<br><br>CONCLUSION: Based on this MR analysis, we found a causal relationship between certain gut microbial communities and PPD. Future clinical studies can further explore the treatment of PPD through the combined use of microorganisms. This not only offers insights into the pathogenesis of PPD but also lays the foundation for utilizing gut microbiota as biotherapeutics in treating neurological disorders.}, }
@article {pmid39281749, year = {2024}, author = {Kang, JW and Khatib, LA and Heston, MB and Dilmore, AH and Labus, JS and Deming, Y and Schimmel, L and Blach, C and McDonald, D and Gonzalez, A and Bryant, M and Sanders, K and Schwartz, A and Ulland, TK and Johnson, SC and Asthana, S and Carlsson, CM and Chin, NA and Blennow, K and Zetterberg, H and Rey, FE and ,  and Kaddurah-Daouk, R and Knight, R and Bendlin, BB}, title = {Gut Microbiome Compositional and Functional Features Associate with Alzheimer's Disease Pathology.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, pmid = {39281749}, support = {R21 AG089348/AG/NIA NIH HHS/United States ; R01 AG092220/AG/NIA NIH HHS/United States ; U19 AG063744/AG/NIA NIH HHS/United States ; S10 OD026929/OD/NIH HHS/United States ; U01 AG061359/AG/NIA NIH HHS/United States ; P30 AG062715/AG/NIA NIH HHS/United States ; R01 AG083883/AG/NIA NIH HHS/United States ; R01 AG070973/AG/NIA NIH HHS/United States ; }, abstract = {BACKGROUND: The gut microbiome is a potentially modifiable factor in Alzheimer's disease (AD); however, understanding of its composition and function regarding AD pathology is limited.<br><br>METHODS: Shallow-shotgun metagenomic data was used to analyze fecal microbiome from participants enrolled in the Wisconsin Microbiome in Alzheimer's Risk Study, leveraging clinical data and cerebrospinal fluid (CSF) biomarkers. Differential abundance and ordinary least squares regression analyses were performed to find differentially abundant gut microbiome features and their associations with CSF biomarkers of AD and related pathologies.<br><br>RESULTS: Gut microbiome composition and function differed between people with AD and cognitively unimpaired individuals. The compositional difference was replicated in an independent cohort. Differentially abundant gut microbiome features were associated with CSF biomarkers of AD and related pathologies.<br><br>DISCUSSION: These findings enhance our understanding of alterations in gut microbial composition and function in AD, and suggest that gut microbes and their pathways are linked to AD pathology.}, }
@article {pmid39252313, year = {2024}, author = {Fan, T and Li, L and Chen, Y}, title = {Causal relationships between gut microbiota and depression/anxiety disorders: A 2-sample Mendelian randomization study.}, journal = {Medicine}, volume = {103}, number = {36}, pages = {e39543}, doi = {10.1097/MD.0000000000039543}, pmid = {39252313}, issn = {1536-5964}, mesh = {*Mendelian Randomization Analysis ; Humans ; *Gastrointestinal Microbiome/genetics ; *Anxiety Disorders/microbiology/genetics ; *Genome-Wide Association Study ; Depressive Disorder/microbiology/genetics ; Depression/microbiology ; }, abstract = {Evidence shows that the composition of the gut microbiota (GM) is associated with depression and anxiety disorders. However, the causal relationship between them remains controversial. To investigate the potential causal relationship between the GM and depression/anxiety disorders and to identify specific bacterial taxa, we conducted a 2-sample Mendelian randomization (MR) analysis on the gut microbiome implicated in depression and anxiety disorders. We incorporated summary data from genome-wide association studies (GWAS) of the microbiome derived from 7738 individuals in the Dutch Microbiome Project and 18,340 individuals in the MiBioGen consortium as our exposure variable. Concurrently, the GWAS of depression and anxiety disorders was employed as our outcome variable. The principal estimates were procured using the inverse-variance weighted test complemented by 4 robust methods: MR Egger, weighted median, simple mode, and weighted mode. In addition, we performed comprehensive sensitivity and directionality analyses. The results showed that 5 bacterial taxa were positively correlated with depression, 6 were negatively correlated; 5 were positively correlated with anxiety disorders, and 11 were negatively correlated. This study provides new insights into the connection between the GM and the pathogenesis of depression and anxiety disorders and offers new perspectives for the diagnosis and treatment of these disorders.}, }
@article {pmid39243281, year = {2024}, author = {Jiang, X and Wang, M and Liu, B and Yang, H and Ren, J and Chen, S and Ye, D and Yang, S and Mao, Y}, title = {Gut microbiota and risk of ankylosing spondylitis.}, journal = {Clinical rheumatology}, volume = {43}, number = {11}, pages = {3351-3360}, pmid = {39243281}, issn = {1434-9949}, support = {81973663//National Natural Science Foundation of China/ ; 82174208//National Natural Science Foundation of China/ ; LY22H260005//Natural Science Foundation of Zhejiang Province/ ; 2023ZL286//Zhejiang Province Traditional Chinese Medical Science and Technology Plan/ ; }, mesh = {*Spondylitis, Ankylosing/microbiology ; Humans ; *Gastrointestinal Microbiome ; *Mendelian Randomization Analysis ; Risk Factors ; Bacteroides/genetics/isolation &amp; purification ; }, abstract = {OBJECTIVE: Observational studies have established a connection between gut microbiota and ankylosing spondylitis (AS) risk; however, whether the observed associations are causal remains unclear. Therefore, we conducted a two-sample Mendelian randomization (MR) analysis to assess the potential causal associations of gut microbiota with AS risk.<br><br>METHODS: Instrumental variants of gut microbiota were obtained from the MiBioGen consortium (n&#x2009;=&#x2009;18,340) and the Dutch Microbiome Project (n&#x2009;=&#x2009;7738). The FinnGen consortium provided genetic association summary statistics for AS, encompassing 2860 cases and 270,964 controls. We used the inverse-variance weighted (IVW) method as the primary analysis, supplemented with the weighted median method, maximum likelihood-based method, MR pleiotropy residual sum and outlier test, and MR-Egger regression. In addition, we conducted a reverse MR analysis to assess the likelihood of reverse causality.<br><br>RESULTS: After the Bonferroni correction, species Bacteroides vulgatus remained statistically significantly associated with AS risk (odds ratio (OR) 1.55, 95% confidence interval (CI) 1.22-1.95, P&#x2009;=&#x2009;2.55&#x2009;&#xd7;&#x2009;10[-4]). Suggestive evidence of associations of eleven bacterial traits with AS risk was also observed (P&#x2009;<&#x2009;0.05 by IVW). Among them, eight were associated with an elevated AS risk (OR 1.37, 95% CI 1.07-1.74, P&#x2009;=&#x2009;0.011 for phylum Verrucomicrobia; OR 1.31, 95% CI 1.03-1.65, P&#x2009;=&#x2009;0.026 for class Verrucomicrobiae; OR 1.17, 95% CI 1.01-1.36, P&#x2009;=&#x2009;0.035 for order Bacillales; OR 1.31, 95% CI 1.03-1.65, P&#x2009;=&#x2009;0.026 for order Verrucomicrobiales; OR 1.43, 95% CI 1.13-1.82, P&#x2009;=&#x2009;0.003 for family Alcaligenaceae; OR 1.31, 95% CI 1.03-1.65, P&#x2009;=&#x2009;0.026 for family Verrucomicrobiaceae; OR 1.31, 95% CI 1.03-1.65, P&#x2009;=&#x2009;0.026 for genus Akkermansia; OR 1.55, 95% CI 1.19-2.02, P&#x2009;=&#x2009;0.001 for species Sutterella wadsworthensis). Three traits exhibited a negative association with AS risk (OR 0.68, 95% CI 0.53-0.88, P&#x2009;=&#x2009;0.003 for genus Dialister; OR 0.84, 95% CI 0.72-0.97, P&#x2009;=&#x2009;0.020 for genus Howardella; OR 0.75, 95% CI 0.59-0.97, P&#x2009;=&#x2009;0.026 for genus Oscillospira). Consistent associations were observed when employing alternate MR methods. In the reverse MR, no statistically significant correlations were detected between AS and these bacterial traits.<br><br>CONCLUSION: Our results revealed the associations of several gut bacterial traits with AS risk, suggesting a potential causal role of gut microbiota in AS development. Nevertheless, additional research is required to clarify the mechanisms by which these bacteria influence AS risk. Key Points &#x2022; The association of gut microbiota with AS risk in observational studies is unclear. &#x2022; This MR analysis revealed associations of 12 gut bacterial traits with AS risk.}, }
@article {pmid39230701, year = {2024}, author = {Hera, MR and Liu, S and Wei, W and Rodriguez, JS and Ma, C and Koslicki, D}, title = {Metagenomic functional profiling: to sketch or not to sketch?.}, journal = {Bioinformatics (Oxford, England)}, volume = {40}, number = {Suppl 2}, pages = {ii165-ii173}, pmid = {39230701}, issn = {1367-4811}, support = {R01 GM146462/GM/NIGMS NIH HHS/United States ; R01GM146462/GF/NIH HHS/United States ; }, mesh = {*Metagenomics/methods ; *Software ; *Algorithms ; *Metagenome/genetics ; Humans ; Microbiota/genetics ; Databases, Genetic ; }, abstract = {MOTIVATION: Functional profiling of metagenomic samples is essential to decipher the functional capabilities of microbial communities. Traditional and more widely used functional profilers in the context of metagenomics rely on aligning reads against a known reference database. However, aligning sequencing reads against a large and fast-growing database is computationally expensive. In general, k-mer-based sketching techniques have been successfully used in metagenomics to address this bottleneck, notably in taxonomic profiling. In this work, we describe leveraging FracMinHash (implemented in sourmash, a publicly available software), a k-mer-sketching algorithm, to obtain functional profiles of metagenome samples.<br><br>RESULTS: We show how pieces of the sourmash software (and the resulting FracMinHash sketches) can be put together in a pipeline to functionally profile a metagenomic sample. We named our pipeline fmh-funprofiler. We report that the functional profiles obtained using this pipeline demonstrate comparable completeness and better purity compared to the profiles obtained using other alignment-based methods when applied to simulated metagenomic data. We also report that fmh-funprofiler is 39-99&#xd7; faster in wall-clock time, and consumes up to 40-55&#xd7; less memory. Coupled with the KEGG database, this method not only replicates fundamental biological insights but also highlights novel signals from the Human Microbiome Project datasets.<br><br>This fast and lightweight metagenomic functional profiler is freely available and can be accessed here: https://github.com/KoslickiLab/fmh-funprofiler. All scripts of the analyses we present in this manuscript can be found on GitHub.}, }
@article {pmid39230322, year = {2024}, author = {Flamholz, AI and Goldford, JE and Richter, PA and Larsson, EM and Jinich, A and Fischer, WW and Newman, DK}, title = {Annotation-free prediction of microbial dioxygen utilization.}, journal = {mSystems}, volume = {9}, number = {10}, pages = {e0076324}, pmid = {39230322}, issn = {2379-5077}, support = {61-1772//Jane Coffin Childs Memorial Fund for Medical Research (JCC)/ ; GBMF4513//Gordon and Betty Moore Foundation (GBMF)/ ; 2127442//National Science Foundation (NSF)/ ; W911NF-22-2-0210//DOD | USA | AFC | CCDC | Army Research Office (ARO)/ ; GT16787//Howard Hughes Medical Institute (HHMI)/ ; }, mesh = {*Oxygen/metabolism/analysis ; Genome, Bacterial/genetics ; Phylogeny ; Molecular Sequence Annotation ; }, abstract = {Aerobes require dioxygen (O2) to grow; anaerobes do not. However, nearly all microbes-aerobes, anaerobes, and facultative organisms alike-express enzymes whose substrates include O2, if only for detoxification. This presents a challenge when trying to assess which organisms are aerobic from genomic data alone. This challenge can be overcome by noting that O2 utilization has wide-ranging effects on microbes: aerobes typically have larger genomes encoding distinctive O2-utilizing enzymes, for example. These effects permit high-quality prediction of O2 utilization from annotated genome sequences, with several models displaying ≈80% accuracy on a ternary classification task for which blind guessing is only 33% accurate. Since genome annotation is compute-intensive and relies on many assumptions, we asked if annotation-free methods also perform well. We discovered that simple and efficient models based entirely on genomic sequence content-e.g., triplets of amino acids-perform as well as intensive annotation-based classifiers, enabling rapid processing of genomes. We further show that amino acid trimers are useful because they encode information about protein composition and phylogeny. To showcase the utility of rapid prediction, we estimated the prevalence of aerobes and anaerobes in diverse natural environments cataloged in the Earth Microbiome Project. Focusing on a well-studied O2 gradient in the Black Sea, we found quantitative correspondence between local chemistry (O2:sulfide concentration ratio) and the composition of microbial communities. We, therefore, suggest that statistical methods like ours might be used to estimate, or "sense," pivotal features of the chemical environment using DNA sequencing data.IMPORTANCEWe now have access to sequence data from a wide variety of natural environments. These data document a bewildering diversity of microbes, many known only from their genomes. Physiology-an organism's capacity to engage metabolically with its environment-may provide a more useful lens than taxonomy for understanding microbial communities. As an example of this broader principle, we developed algorithms that accurately predict microbial dioxygen utilization directly from genome sequences without annotating genes, e.g., by considering only the amino acids in protein sequences. Annotation-free algorithms enable rapid characterization of natural samples, highlighting quantitative correspondence between sequences and local O2 levels in a data set from the Black Sea. This example suggests that DNA sequencing might be repurposed as a multi-pronged chemical sensor, estimating concentrations of O2 and other key facets of complex natural settings.}, }
@article {pmid39226947, year = {2024}, author = {Di, J and Xi, Y and Wu, Y and Di, Y and Xing, X and Zhang, Z and Xiang, C}, title = {Gut microbiota metabolic pathways: Key players in knee osteoarthritis development.}, journal = {Experimental gerontology}, volume = {196}, number = {}, pages = {112566}, doi = {10.1016/j.exger.2024.112566}, pmid = {39226947}, issn = {1873-6815}, mesh = {*Gastrointestinal Microbiome/physiology ; Humans ; *Osteoarthritis, Knee/metabolism/microbiology ; *Mendelian Randomization Analysis ; Polymorphism, Single Nucleotide ; Metabolic Networks and Pathways ; Risk Factors ; }, abstract = {OBJECTIVE: To confirm the causality of gut microbiota pathway abundance and knee osteoarthritis (KOA).<br><br>METHODS: Microbial metabolic pathways were taken as exposures, with data from the Dutch Microbiome Project (DMP). Data on KOA from the UK Biobank were utilized as endpoints. In addition, we extracted significant and independent single nucleotide polymorphisms as instrumental variables. Two-sample Mendelian randomization (MR) analysis was applied to explore the causal relationship between gut microbiota pathway abundance and KOA, and MR-Egger and weighted median were used as additional validation of the MR results. Meanwhile, Cochran Q, MR-Egger intercept, MR-PRESSO, and leave-one-out were used to perform sensitivity analyses on the MR results.<br><br>RESULTS: MR results showed that enterobactin biosynthesis, diacylglycerol biosynthesis I, Clostridium acetobutylicum acidogenic fermentation, glyoxylate bypass and tricarboxylic acid cycle were the risk factors for KOA. (OR&#xa0;=&#xa0;1.13,95%CI&#xa0;=&#xa0;1.04-1.23;OR&#xa0;=&#xa0;1.12,95%CI&#xa0;=&#xa0;1.04-1.20;OR&#xa0;=&#xa0;1.14,95%CI&#xa0;=&#xa0;1.04-1.26; OR&#xa0;=&#xa0;1.06,95%CI&#xa0;=&#xa0;1.00-1.12) However, adenosylcobalamin salvage from cobinamide I, hexitol fermentation to lactate formate ethanol and acetate, purine nucleotides degradation II aerobic, L tryptophan biosynthesis and inosine 5 phosphate biosynthesis III pathway showed significant protection against KOA. (OR&#xa0;=&#xa0;0.93,95%CI&#xa0;=&#xa0;0.86-1.00;OR&#xa0;=&#xa0;0.94,95%CI&#xa0;=&#xa0;0.88-1.00;OR&#xa0;=&#xa0;0.91,95%CI&#xa0;=&#xa0;0.86-0.97;OR&#xa0;=&#xa0;0.95,95%CI&#xa0;=&#xa0;0.92-0.99; OR&#xa0;=&#xa0;0.91, 95%CI&#xa0;=&#xa0;0.85-0.98) Further multiplicity and sensitivity analyses demonstrated the robustness of the results.<br><br>CONCLUSION: Our study identified specific metabolic pathways in gut microbiota that promote or inhibit KOA, which provides the most substantial evidence-based medical evidence for the pathogenesis and prevention of KOA.}, }
@article {pmid39209213, year = {2024}, author = {Koellsch, C and Poulin, R and Salloum, PM}, title = {What shapes a microbiome? Differences in bacterial communities associated with helminth-amphipod interactions.}, journal = {International journal for parasitology}, volume = {54}, number = {14}, pages = {733-742}, doi = {10.1016/j.ijpara.2024.08.005}, pmid = {39209213}, issn = {1879-0135}, mesh = {Animals ; *Host-Parasite Interactions ; *Acanthocephala/physiology/genetics ; *Amphipoda/parasitology/microbiology ; *Microbiota ; *Cestoda/genetics/physiology/classification ; *RNA, Ribosomal, 16S/genetics ; Bacteria/classification/genetics/isolation &amp; purification ; Hemolymph/microbiology/parasitology ; Female ; Helminths/genetics/classification/physiology/isolation &amp; purification ; Male ; }, abstract = {The fast technological advances of molecular tools have enabled us to uncover a new dimension hidden within parasites and their hosts: their microbiomes. Increasingly, parasitologists characterise host microbiome changes in the face of parasitic infections, revealing the potential of these microscopic fast-evolving entities to influence host-parasite interactions. However, most of the changes in host microbiomes seem to depend on the host and parasite species in question. Furthermore, we should understand the relative role of parasitic infections as microbiome modulators when compared with other microbiome-impacting factors (e.g., host size, age, sex). Here, we characterised the microbiome of a single intermediate host species infected by two parasites belonging to different phyla: the acanthocephalan Plagiorhynchus allisonae and a dilepidid cestode, both infecting Transorchestia serrulata amphipods collected simultaneously from the same locality. We used the v4 hypervariable region of the 16S rRNA prokaryotic gene to identify the hemolymph bacterial community of uninfected, acanthocephalan-infected, and cestode-infected amphipods, as well as the bacteria in the amphipods' immediate environment and in the parasites infecting them. Our results show that parasitic infections were more strongly associated with differences in host bacterial community richness than amphipod size, presence of amphipod eggs in female amphipods, and even parasite load. Amphipods infected by acanthocephalans had the most divergent bacterial community, with a marked decrease in alpha diversity compared with cestode-infected and uninfected hosts. In accordance with the species-specific nature of microbiome changes in parasitic infections, we found unique microbial taxa associating with hosts infected by each parasite species, as well as taxa only shared between a parasite species and their infected hosts. However, there were some bacterial taxa detected in all parasitised amphipods (regardless of the parasite species), but not in uninfected amphipods or the environment. We propose that shared bacteria associated with all hosts parasitised by distantly related helminths may be important either in helping host defences or parasites' success, and could thus interact with host-parasite evolution.}, }
@article {pmid39207108, year = {2024}, author = {Crouch, AL and Monsey, L and Rambeau, M and Ramos, C and Yracheta, JM and Anderson, MZ}, title = {Metagenomic discovery of microbial eukaryotes in stool microbiomes.}, journal = {mBio}, volume = {15}, number = {10}, pages = {e0206324}, pmid = {39207108}, issn = {2150-7511}, support = {//Ohio State University (OSU)/ ; 2046863//National Science Foundation (NSF)/ ; //Chan Zuckerberg Initiative (CZI)/ ; }, mesh = {Humans ; *Metagenomics/methods ; *Feces/microbiology ; *Eukaryota/genetics/classification/isolation &amp; purification ; Gastrointestinal Microbiome/genetics ; Metagenome ; Fungi/genetics/classification/isolation &amp; purification ; Sequence Analysis, DNA/methods ; Microbiota/genetics ; }, abstract = {Host-associated microbiota form complex microbial communities that are increasingly associated with host behavior and disease. While these microbes include bacterial, archaeal, viral, and eukaryotic constituents, most studies have focused on bacteria due to their dominance in the human host and available tools for investigation. Accumulating evidence suggests microbial eukaryotes in the microbiome play pivotal roles in host health, but our understandings of these interactions are limited to a few readily identifiable taxa because of technical limitations in unbiased eukaryote exploration. Here, we combined cell sorting, optimized eukaryotic cell lysis, and shotgun sequencing to accelerate metagenomic discovery and analysis of host-associated microbial eukaryotes. Using synthetic communities with a 1% microbial eukaryote representation, the eukaryote-optimized cell lysis and DNA recovery method alone yielded a 38-fold increase in eukaryotic DNA. Automated sorting of eukaryotic cells from stool samples of healthy adults increased the number of microbial eukaryote reads in metagenomic pools by up to 28-fold compared to commercial kits. Read frequencies for identified fungi increased by 10,000× on average compared to the Human Microbiome Project and allowed for the identification of novel taxa, de novo assembly of contigs from previously unknown microbial eukaryotes, and gene prediction from recovered genomic segments. These advances pave the way for the unbiased inclusion of microbial eukaryotes in deciphering determinants of health and disease in the host-associated microbiome.IMPORTANCEMicrobial eukaryotes are common constituents of the human gut where they can contribute to local ecology and host health, but they are often overlooked in microbiome studies. The lack of attention is due to current technical limitations that are heavily biased or poorly recovered DNA from microbial eukaryotes. We developed a method to increase the representation of these eukaryotes in metagenomic sequencing of microbiome samples that allows to improve their detection compared to prior methods and allows for the identification of new species. Application of the technique to gut microbiome samples improved detection of fungi, protists, and helminths. New eukaryotic taxa and their encoded genes could be identified by sequencing a small number of samples. This approach can improve the inclusion of eukaryotes into microbiome research.}, }
@article {pmid39139765, year = {2024}, author = {Sun, Y and Dong, H and Sun, C and Du, D and Gao, R and Voevoda, M and Knyazev, R and Wu, N}, title = {Investigating the association between gut microbiome and aortic aneurysm diseases: a bidirectional two-sample Mendelian randomization analysis.}, journal = {Frontiers in cellular and infection microbiology}, volume = {14}, number = {}, pages = {1406845}, pmid = {39139765}, issn = {2235-2988}, mesh = {*Mendelian Randomization Analysis ; Humans ; *Gastrointestinal Microbiome/genetics ; *Genome-Wide Association Study ; Aortic Aneurysm, Abdominal/microbiology/genetics ; Aortic Aneurysm/microbiology/genetics ; Bacteria/classification/genetics/isolation &amp; purification ; Aortic Aneurysm, Thoracic/microbiology/genetics ; Aortic Dissection/microbiology ; }, abstract = {OBJECTIVE: This study aims to investigate the associations between specific bacterial taxa of the gut microbiome and the development of aortic aneurysm diseases, utilizing Mendelian Randomization (MR) to explore these associations and overcome the confounding factors commonly present in observational studies.<br><br>METHODS: Employing the largest available gut microbiome and aortic aneurysm Genome-Wide Association Study databases, including MiBioGen, Dutch Microbiome Project, FinnGen, UK Biobank, and Michigan Genomics Initiative, this study performs two-sample bidirectional MR analyses. Instrumental variables, linked to microbiome taxa at significant levels, were selected for identifying relationships with abdominal aortic aneurysms (AAA), thoracic aortic aneurysms (TAA), and aortic dissection (AD). Methods like inverse variance weighted, MR-PRESSO, MR-Egger, weighted median, simple mode, and mode-based estimate were used for MR analysis. Heterogeneity was assessed with the Cochran Q test. MR-Egger regression and MR-PRESSO addressed potential unbalanced horizontal pleiotropy.<br><br>RESULTS: The analysis did not find any evidence of statistically significant associations between the gut microbiome and aortic aneurysm diseases after adjusting for the false discovery rate (FDR). Specifically, while initial results suggested correlations between 19 taxa and AAA, 25 taxa and TAA, and 13 taxa with AD, these suggested associations did not hold statistical significance post-FDR correction. Therefore, the role of individual gut microbial taxa as independent factors in the development and progression of aortic aneurysm diseases remains inconclusive. This finding underscores the necessity for larger sample sizes and more comprehensive studies to further investigate these potential links.<br><br>CONCLUSION: The study emphasizes the complex relationship between the gut microbiome and aortic aneurysm diseases. Although no statistically significant associations were found after FDR correction, the findings provide valuable insights and highlight the importance of considering gut microbiota in aortic aneurysm diseases research. Understanding these interactions may eventually contribute to identifying new therapeutic and preventive strategies for aortic aneurysm diseases.}, }
@article {pmid39053136, year = {2024}, author = {Gholamzad, A and Khakpour, N and Hashemi, SMA and Goudarzi, Y and Ahmadi, P and Gholamzad, M and Mohammadi, M and Hashemi, M}, title = {Exploring the virome: An integral part of human health and disease.}, journal = {Pathology, research and practice}, volume = {260}, number = {}, pages = {155466}, doi = {10.1016/j.prp.2024.155466}, pmid = {39053136}, issn = {1618-0631}, mesh = {Humans ; *Virome ; *Gastrointestinal Microbiome ; Inflammatory Bowel Diseases/virology ; }, abstract = {The human microbiome is a complex network of microorganisms that includes viruses, bacteria, and fungi. The gut virome is an essential component of the immune system, which is responsible for regulating the growth and responses of the host's immune system. The virome maintains a crucial role in the development of numerous diseases, including inflammatory bowel disease (IBD), Crohn's disease, and neurodegenerative disorders. The human virome has emerged as a promising biomarker and therapeutic target. This comprehensive review summarizes the present understanding of the virome and its implications in matters of health and disease, with a focus on the Human Microbiome Project.}, }
@article {pmid39040076, year = {2024}, author = {Onwuka, S and Bravo-Merodio, L and Gkoutos, GV and Acharjee, A}, title = {Explainable AI-prioritized plasma and fecal metabolites in inflammatory bowel disease and their dietary associations.}, journal = {iScience}, volume = {27}, number = {7}, pages = {110298}, pmid = {39040076}, issn = {2589-0042}, abstract = {Fecal metabolites effectively discriminate inflammatory bowel disease (IBD) and show differential associations with diet. Metabolomics and AI-based models, including explainable AI (XAI), play crucial roles in understanding IBD. Using datasets from the UK Biobank and the Human Microbiome Project Phase II IBD Multi'omics Database (HMP2 IBDMDB), this study uses multiple machine learning (ML) classifiers and Shapley additive explanations (SHAP)-based XAI to prioritize plasma and fecal metabolites and analyze their diet correlations. Key findings include the identification of discriminative metabolites like glycoprotein acetyl and albumin in plasma, as well as nicotinic acid metabolites andurobilin in feces. Fecal metabolites provided a more robust disease predictor model (AUC [95%]: 0.93 [0.87-0.99]) compared to plasma metabolites (AUC [95%]: 0.74 [0.69-0.79]), with stronger and more group-differential diet-metabolite associations in feces. The study validates known metabolite associations and highlights the impact of IBD on the interplay between gut microbial metabolites and diet.}, }
@article {pmid39027091, year = {2024}, author = {Li, J and Li, J and Liu, Y and Zeng, J and Liu, Y and Wu, Y}, title = {Large-scale bidirectional Mendelian randomization study identifies new gut microbiome significantly associated with immune thrombocytopenic purpura.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1423951}, pmid = {39027091}, issn = {1664-302X}, abstract = {INTRODUCTION: A variety of studies have shown a link between the gut microbiota and autoimmune diseases, but the causal relationship with Henoch-Schönlein purpura (HSP) and immune thrombocytopenic purpura (ITP) is unknown.<br><br>METHODS: This study investigated the bidirectional causality between gut microbiota and HSP and ITP using Mendelian randomization (MR). Large-scale genetic data of gut microbiota at phylum to species level from the MiBioGen consortium and the Dutch Microbiome Project were utilized. Genome-wide association studies (GWAS) summary statistics for HSP and ITP came from FinnGen R10. Various MR methods were applied to infer causal relationships, including inverse variance weighted (IVW), maximum likelihood (ML), cML-MA, MR-Egger, weighted median, weighted model, and MR-PRESSO. Multiple sensitivity analyses and Bonferroni correction were conducted to enhance robustness and reliability.<br><br>RESULTS: Based on the IVW estimates, 23 bacterial taxa were identified to have suggestive associations with HSP and ITP. Remarkably, after Bonferroni correction, family Alcaligenaceae (OR&#x2009;=&#x2009;2.86, 95% CI&#x2009;=&#x2009;1.52-5.37; IVW, p&#x2009;=&#x2009;1.10&#x2009;&#xd7;&#x2009;10[-3], ML, p&#x2009;=&#x2009;1.40&#x2009;&#xd7;&#x2009;10[-3]) was significantly associated with ITP as a risk factor, while family Bacteroidales S24 7group (OR&#x2009;=&#x2009;0.46, 95% CI&#x2009;=&#x2009;0.29-0.74; IVW, p&#x2009;=&#x2009;1.40&#x2009;&#xd7;&#x2009;10[-3]) was significantly associated with ITP as a protective factor. No significant associations between HSP and ITP and gut microbiota were found in reverse analyses.<br><br>CONCLUSION: Our study provides evidence of causal effects of gut microbiota on HSP and ITP, highlighting the importance of further research to clarify the underlying mechanisms and develop targeted therapeutic interventions for these autoimmune diseases.}, }
@article {pmid38989853, year = {2024}, author = {Koellsch, C and Poulin, R and Salloum, PM}, title = {Microbial artists: the role of parasite microbiomes in explaining colour polymorphism among amphipods and potential link to host manipulation.}, journal = {Journal of evolutionary biology}, volume = {37}, number = {9}, pages = {1009-1022}, doi = {10.1093/jeb/voae085}, pmid = {38989853}, issn = {1420-9101}, mesh = {Animals ; *Amphipoda/microbiology/parasitology ; *Host-Parasite Interactions ; *Microbiota ; Acanthocephala/genetics/physiology ; Pigmentation/genetics ; Color ; }, abstract = {Parasite infections are increasingly reported to change the microbiome of the parasitized hosts, while parasites bring their own microbes to what can be a multi-dimensional interaction. For instance, a recent hypothesis suggests that the microbial communities harboured by parasites may play a role in the well-documented ability of many parasites to manipulate host phenotype, and explain why the degree to which host phenotype is altered varies among conspecific parasites. Here, we explored whether the microbiomes of both hosts and parasites are associated with variation in host manipulation by parasites. Using colour quantification methods applied to digital images, we investigated colour variation among uninfected Transorchestia serrulata amphipods, as well as amphipods infected with Plagiorhynchus allisonae acanthocephalans and with a dilepidid cestode. We then characterized the bacteriota of amphipod hosts and of their parasites, looking for correlations between host phenotype and the bacterial taxa associated with hosts and parasites. We found large variation in amphipod colours, and weak support for a direct impact of parasites on the colour of their hosts. Conversely, and most interestingly, the parasite's bacteriota was more strongly correlated with colour variation among their amphipod hosts, with potential impact of amphipod-associated bacteria as well. Some bacterial taxa found associated with amphipods and parasites may have the ability to synthesize pigments, and we propose they may interact with colour determination in the amphipods. This study provides correlational support for an association between the parasite's microbiome and the evolution of host manipulation by parasites and host-parasite interactions more generally.}, }
@article {pmid38977973, year = {2024}, author = {Zhao, Q and Baranova, A and Cao, H and Zhang, F}, title = {Gut microbiome and major depressive disorder: insights from two-sample Mendelian randomization.}, journal = {BMC psychiatry}, volume = {24}, number = {1}, pages = {493}, pmid = {38977973}, issn = {1471-244X}, mesh = {Humans ; *Gastrointestinal Microbiome/genetics ; *Depressive Disorder, Major/microbiology/genetics ; *Mendelian Randomization Analysis ; *Genome-Wide Association Study ; }, abstract = {BACKGROUND: Existing evidence suggests that alterations in the gut microbiome are closely associated with major depressive disorder (MDD). We aimed to reveal the causal relationships between MDD and various microbial taxa in the gut.<br><br>METHODS: We used the two-sample Mendelian randomization (TSMR) to explore the bidirectional causal effects between gut microbiota and MDD. The genome-wide association studies summary results of gut microbiota were obtained from two large consortia, the MibioGen consortium and the Dutch Microbiome Project, which we analyzed separately.<br><br>RESULTS: Our TSMR analysis identified 10 gut bacterial taxa that were protective against MDD, including phylum Actinobacteria, order Clostridiales, and family Bifidobacteriaceae (OR: 0.96&#x2009;&#x223c;&#x2009;0.98). Ten taxa were associated with an increased risk of MDD, including phyla Firmicutes and Proteobacteria, class Actinobacteria, and genus Alistipes (OR: 1.01&#x2009;&#x223c;&#x2009;1.09). On the other hand, MDD may decrease the abundance of 12 taxa, including phyla Actinobacteria and Firmicutes, families Bifidobacteriaceae and Defluviitaleaceae (OR: 0.63&#x2009;&#x223c;&#x2009;0.88). MDD may increase the abundance of 8 taxa, including phylum Bacteroidetes, genera Parabacteroides, and Bacteroides (OR: 1.12&#x2009;&#x223c;&#x2009;1.43).<br><br>CONCLUSIONS: Our study supports that there are mutual causal relationships between certain gut microbiota and the development of MDD suggesting that gut microbiota may be targeted in the treatment of MDD.}, }
@article {pmid38962750, year = {2024}, author = {Schweickart, A and Batra, R and Neth, BJ and Martino, C and Shenhav, L and Zhang, AR and Shi, P and Karu, N and Huynh, K and Meikle, PJ and Schimmel, L and Dilmore, AH and Blennow, K and Zetterberg, H and Blach, C and Dorrestein, PC and Knight, R and ,  and Craft, S and Kaddurah-Daouk, R and Krumsiek, J}, title = {Serum and CSF metabolomics analysis shows Mediterranean Ketogenic Diet mitigates risk factors of Alzheimer's disease.}, journal = {npj metabolic health and disease}, volume = {2}, number = {1}, pages = {15}, pmid = {38962750}, issn = {2948-2828}, support = {R01 AG046171/AG/NIA NIH HHS/United States ; R01 AG069901/AG/NIA NIH HHS/United States ; U19 AG063744/AG/NIA NIH HHS/United States ; P30 AG049638/AG/NIA NIH HHS/United States ; UL1 TR001420/TR/NCATS NIH HHS/United States ; RF1 AG059093/AG/NIA NIH HHS/United States ; U01 AG061359/AG/NIA NIH HHS/United States ; RF1 AG057452/AG/NIA NIH HHS/United States ; RF1 AG058942/AG/NIA NIH HHS/United States ; RF1 AG051550/AG/NIA NIH HHS/United States ; }, abstract = {Alzheimer's disease (AD) is influenced by a variety of modifiable risk factors, including a person's dietary habits. While the ketogenic diet (KD) holds promise in reducing metabolic risks and potentially affecting AD progression, only a few studies have explored KD's metabolic impact, especially on blood and cerebrospinal fluid (CSF). Our study involved participants at risk for AD, either cognitively normal or with mild cognitive impairment. The participants consumed both a modified Mediterranean Ketogenic Diet (MMKD) and the American Heart Association diet (AHAD) for 6 weeks each, separated by a 6-week washout period. We employed nuclear magnetic resonance (NMR)-based metabolomics to profile serum and CSF and metagenomics profiling on fecal samples. While the AHAD induced no notable metabolic changes, MMKD led to significant alterations in both serum and CSF. These changes included improved modifiable risk factors, like increased HDL-C and reduced BMI, reversed serum metabolic disturbances linked to AD such as a microbiome-mediated increase in valine levels, and a reduction in systemic inflammation. Additionally, the MMKD was linked to increased amino acid levels in the CSF, a breakdown of branched-chain amino acids (BCAAs), and decreased valine levels. Importantly, we observed a strong correlation between metabolic changes in the CSF and serum, suggesting a systemic regulation of metabolism. Our findings highlight that MMKD can improve AD-related risk factors, reverse some metabolic disturbances associated with AD, and align metabolic changes across the blood-CSF barrier.}, }
@article {pmid38927665, year = {2024}, author = {Li, X and Xu, B and Yang, H and Zhu, Z}, title = {Gut Microbiota, Human Blood Metabolites, and Esophageal Cancer: A Mendelian Randomization Study.}, journal = {Genes}, volume = {15}, number = {6}, pages = {}, pmid = {38927665}, issn = {2073-4425}, mesh = {Humans ; *Mendelian Randomization Analysis ; *Esophageal Neoplasms/genetics/microbiology/blood ; *Gastrointestinal Microbiome/genetics ; *Genome-Wide Association Study ; Metabolome ; }, abstract = {BACKGROUND: Unbalances in the gut microbiota have been proposed as a possible cause of esophageal cancer (ESCA), yet the exact causal relationship remains unclear.<br><br>PURPOSE: To investigate the potential causal relationship between the gut microbiota and ESCA with Mendelian randomization (MR) analysis.<br><br>METHODS: Genome-wide association studies (GWASs) of 207 gut microbial taxa (5 phyla, 10 classes, 13 orders, 26 families, 48 genera, and 105 species) and 205 gut microbiota metabolic pathways conducted by the Dutch Microbiome Project (DMP) and a FinnGen cohort GWAS of esophageal cancer specified the summary statistics. To investigate the possibility of a mediation effect between the gut microbiota and ESCA, mediation MR analyses were performed for 1091 blood metabolites and 309 metabolite ratios.<br><br>RESULTS: MR analysis indicated that the relative abundance of 10 gut microbial taxa was associated with ESCA but all the 12 gut microbiota metabolic pathways with ESCA indicated no statistically significant association existing. Two blood metabolites and a metabolite ratio were discovered to be mediating factors in the pathway from gut microbiota to ESCA.<br><br>CONCLUSION: This research indicated the potential mediating effects of blood metabolites and offered genetic evidence in favor of a causal correlation between gut microbiota and ESCA.}, }
@article {pmid38909071, year = {2024}, author = {Pechlivanis, N and Karakatsoulis, G and Kyritsis, K and Tsagiopoulou, M and Sgardelis, S and Kappas, I and Psomopoulos, F}, title = {Microbial co-occurrence network demonstrates spatial and climatic trends for global soil diversity.}, journal = {Scientific data}, volume = {11}, number = {1}, pages = {672}, pmid = {38909071}, issn = {2052-4463}, mesh = {*Soil Microbiology ; *Microbiota ; *Climate ; Bacteria ; Biodiversity ; }, abstract = {Despite recent research efforts to explore the co-occurrence patterns of diverse microbes within soil microbial communities, a substantial knowledge-gap persists regarding global climate influences on soil microbiota behaviour. Comprehending co-occurrence patterns within distinct geoclimatic groups is pivotal for unravelling the ecological structure of microbial communities, that are crucial for preserving ecosystem functions and services. Our study addresses this gap by examining global climatic patterns of microbial diversity. Using data from the Earth Microbiome Project, we analyse a meta-community co-occurrence network for bacterial communities. This method unveils substantial shifts in topological features, highlighting regional and climatic trends. Arid, Polar, and Tropical zones show lower diversity but maintain denser networks, whereas Temperate and Cold zones display higher diversity alongside more modular networks. Furthermore, it identifies significant co-occurrence patterns across diverse climatic regions. Central taxa associated with different climates are pinpointed, highlighting climate's pivotal role in community structure. In conclusion, our study identifies significant correlations between microbial interactions in diverse climatic regions, contributing valuable insights into the intricate dynamics of soil microbiota.}, }
@article {pmid38878076, year = {2024}, author = {Jawanda, IK and Soni, T and Kumari, S and Prabha, V}, title = {The evolving facets of vaginal microbiota transplantation: reinvigorating the unexplored frontier amid complex challenges.}, journal = {Archives of microbiology}, volume = {206}, number = {7}, pages = {306}, pmid = {38878076}, issn = {1432-072X}, mesh = {Animals ; Female ; Humans ; Anti-Bacterial Agents/therapeutic use ; *Dysbiosis/microbiology/therapy ; Lactobacillus ; *Microbiota ; *Probiotics/administration &amp; dosage ; *Vagina/microbiology ; }, abstract = {In an age of cutting-edge sequencing methods and worldwide endeavors such as The Human Microbiome Project and MetaHIT, the human microbiome stands as a complex and diverse community of microorganisms. A central theme in current scientific inquiry revolves around reinstating a balanced microbial composition, referred to as "eubiosis," as a targeted approach for treating vast array of diseases. Vaginal Microbiota Transplantation (VMT), inspired by the success of fecal microbiota transplantation, emerges as an innovative therapy addressing vaginal dysbacteriosis by transferring the complete microbiota from a healthy donor. Antibiotics, while effective, pose challenges with adverse effects, high recurrence rates, and potential harm to beneficial Lactobacillus strains. Continued antibiotic usage also sparks worries regarding the development of resistant strains. Probiotics, though showing promise, exhibit inconsistency in treating multifactorial diseases, and concerns linger about their suitability for diverse genetic backgrounds. Given the recurrent challenges associated with antibiotic and probiotic treatments, VMT emerges as an imperative alternative, offering a unique and promising avenue for efficiently and reliably managing vaginal dysbiosis among a majority of women. This review critically evaluates findings from both animal and human studies, offering nuanced insights into the efficacy and challenges of VMT. An extensive analysis of clinical trials, provides a current overview of ongoing and completed trials, shedding light on the evolving clinical landscape and therapeutic potential of VMT. Delving into the origins, mechanisms, and optimized protocols of VMT, the review underscores the imperative for sustained research efforts to advance this groundbreaking gynecological therapy.}, }
@article {pmid38855762, year = {2024}, author = {Huang, Y and Kang, Z and He, Y and Qiu, Y and Song, Y and Liu, W}, title = {Association between gut microbiota and common overlapping gastrointestinal disorders: a bidirectional two-sample Mendelian randomization study.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1343564}, pmid = {38855762}, issn = {1664-302X}, abstract = {BACKGROUND: The main functional gastrointestinal disorders (FGIDs) include functional dyspepsia (FD) and irritable bowel syndrome (IBS), which often present overlapping symptoms with gastroesophageal reflux disease (GERD), posing a challenge for clinical diagnosis and treatment. The gut microbiota is closely associated with FGIDs and GERD, although the causal relationship has not been fully elucidated. Therefore, we aimed to investigate the potential causal relationship using bidirectional two-sample Mendelian randomization (MR) analysis.<br><br>MATERIALS AND METHODS: The genetic data of the 211 gut microbiota were obtained from the MiBioGen consortium (N&#x2009;=&#x2009;14,306, from phylum to genus level) and species level of gut microbiota were acquired from the Dutch Microbiome Project (N&#x2009;=&#x2009;7,738). For FD and IBS, we utilized the FinnGen consortium, whereas, for GERD data analysis, we obtained the IEU OpenGWAS project. The inverse-variance weighted (IVW) method was used as the primary method to calculate causal effect values. Sensitivity analyses were also performed to confirm the robustness of the primary findings of the MR analyses. Moreover, a reverse MR analysis was conducted to assess the likelihood of reverse causality.<br><br>RESULTS: Combining the results of the preliminary and sensitivity analyses, we identified that 8 gut microbial taxa were associated with FD. Genus Lachnospiraceae NK4A136 group (p&#x2009;=&#x2009;3.63&#x2009;&#xd7;&#x2009;10[-3]) and genus Terrisporobacter (p&#x2009;=&#x2009;1.13&#x2009;&#xd7;&#x2009;10[-3]) were strongly associated with FD. At the same time, we found that 8 gut microbial taxa were associated with IBS. Family Prevotellaceae (p&#x2009;=&#x2009;2.44&#x2009;&#xd7;&#x2009;10[-3]) and species Clostridium leptum (p&#x2009;=&#x2009;7.68&#x2009;&#xd7;&#x2009;10[-3]) display a robust correlation with IBS. In addition, 5 gut microbial taxa were associated with GERD using the IVW approach. In the reverse MR analysis, 2 gut microbial taxa were found to be associated with FD, 5 gut microbial taxa were found to be associated with IBS, and 21 gut microbial taxa were found to be associated with GERD.<br><br>CONCLUSION: The study reveals the potential causal effects of specific microbial taxa on FD, IBS, and GERD and may offer novel insights into the diagnosis and treatment of these conditions.}, }
@article {pmid38849944, year = {2024}, author = {Ornish, D and Madison, C and Kivipelto, M and Kemp, C and McCulloch, CE and Galasko, D and Artz, J and Rentz, D and Lin, J and Norman, K and Ornish, A and Tranter, S and DeLamarter, N and Wingers, N and Richling, C and Kaddurah-Daouk, R and Knight, R and McDonald, D and Patel, L and Verdin, E and E Tanzi, R and Arnold, SE}, title = {Effects of intensive lifestyle changes on the progression of mild cognitive impairment or early dementia due to Alzheimer's disease: a randomized, controlled clinical trial.}, journal = {Alzheimer's research &amp; therapy}, volume = {16}, number = {1}, pages = {122}, pmid = {38849944}, issn = {1758-9193}, support = {P30 AG062429/AG/NIA NIH HHS/United States ; GC-202102-2021459//The Alzheimer's Drug Discovery Foundation/ ; funded by NIA U19AG063744 &amp; U01AG061359 &amp; R01AG081322//Alzheimer Gut Microbiome Project/ ; }, mesh = {Humans ; Male ; Female ; Aged ; *Cognitive Dysfunction ; *Alzheimer Disease/psychology ; *Disease Progression ; Aged, 80 and over ; *Life Style ; Middle Aged ; Dementia/psychology ; Amyloid beta-Peptides/blood ; Neuropsychological Tests ; Treatment Outcome ; }, abstract = {BACKGROUND: Evidence links lifestyle factors with Alzheimer's disease (AD). We report the first randomized, controlled clinical trial to determine if intensive lifestyle changes may beneficially affect the progression of mild cognitive impairment (MCI) or early dementia due to AD.<br><br>METHODS: A 1:1 multicenter randomized controlled phase 2 trial, ages 45-90 with MCI or early dementia due to AD and a Montreal Cognitive Assessment (MoCA) score of 18 or higher. The primary outcome measures were changes in cognition and function tests: Clinical Global Impression of Change (CGIC), Alzheimer's Disease Assessment Scale (ADAS-Cog), Clinical Dementia Rating-Sum of Boxes (CDR-SB), and Clinical Dementia Rating Global (CDR-G) after 20 weeks of an intensive multidomain lifestyle intervention compared to a wait-list usual care control group. ADAS-Cog, CDR-SB, and CDR-Global scales were compared using a Mann-Whitney-Wilcoxon rank-sum test, and CGIC was compared using Fisher's exact test. Secondary outcomes included plasma A&#x3b2;42/40 ratio, other biomarkers, and correlating lifestyle with the degree of change in these measures.<br><br>RESULTS: Fifty-one AD patients enrolled, mean age 73.5. No significant differences in any measures at baseline. Only two patients withdrew. All patients had plasma A&#x3b2;42/40 ratios <0.0672 at baseline, strongly supporting AD diagnosis. After 20 weeks, significant between-group differences in the CGIC (p=&#xa0;0.001), CDR-SB (p=&#xa0;0.032), and CDR Global (p= 0.037) tests and borderline significance in the ADAS-Cog test (p= 0.053). CGIC, CDR Global, and ADAS-Cog showed improvement in cognition and function and CDR-SB showed significantly less progression, compared to the control group which worsened in all four measures. A&#x3b2;42/40 ratio increased in the intervention group and decreased in the control group (p = 0.003). There was a significant correlation between lifestyle and both cognitive function and the plasma A&#x3b2;42/40 ratio. The microbiome improved only in the intervention group (p <0.0001).<br><br>CONCLUSIONS: Comprehensive lifestyle changes may significantly improve cognition and function after 20 weeks in many patients with MCI or early dementia due to AD.<br><br>TRIAL REGISTRATION: Approved by Western Institutional Review Board on 12/31/2017 (#20172897) and by Institutional Review Boards of all sites. This&#xa0;study was registered retrospectively with clinicaltrials.gov on October 8, 2020 (NCT04606420, ID: 20172897).}, }
@article {pmid38849517, year = {2024}, author = {Jansen, R and Milaneschi, Y and Schranner, D and Kastenmuller, G and Arnold, M and Han, X and Dunlop, BW and ,  and Rush, AJ and Kaddurah-Daouk, R and Penninx, BWJH}, title = {The metabolome-wide signature of major depressive disorder.}, journal = {Molecular psychiatry}, volume = {29}, number = {12}, pages = {3722-3733}, pmid = {38849517}, issn = {1476-5578}, support = {636310017//ZonMw (Netherlands Organisation for Health Research and Development)/ ; }, mesh = {Humans ; *Depressive Disorder, Major/metabolism/genetics ; Female ; Male ; *Metabolome ; Adult ; Middle Aged ; Metabolomics/methods ; Netherlands ; Lipid Metabolism/physiology/genetics ; Cohort Studies ; }, abstract = {Major Depressive Disorder (MDD) is a common, frequently chronic condition characterized by substantial molecular alterations and pathway dysregulations. Single metabolite and targeted metabolomics platforms have revealed several metabolic alterations in depression, including energy metabolism, neurotransmission, and lipid metabolism. More comprehensive coverage of the metabolome is needed to further specify metabolic dysregulations in depression and reveal previously untargeted mechanisms. Here, we measured 820 metabolites using the metabolome-wide Metabolon platform in 2770 subjects from a large Dutch clinical cohort with extensive clinical phenotyping (1101 current MDD, 868 remitted MDD, 801 healthy controls) at baseline, which were repeated in 1805 subjects at 6-year follow up (327 current MDD, 1045 remitted MDD, 433 healthy controls). MDD diagnosis was based on DSM-IV psychiatric interviews. Depression severity was measured with the Inventory of Depressive Symptomatology Self-report. Associations between metabolites and MDD status and depression severity were assessed at baseline and at 6-year follow-up. At baseline, 139 and 126 metabolites were associated with current MDD status and depression severity, respectively, with 79 overlapping metabolites. Adding body mass index and lipid-lowering medication to the models changed results only marginally. Among the overlapping metabolites, 34 were confirmed in internal replication analyses using 6-year follow-up data. Downregulated metabolites were enriched with long-chain monounsaturated (P = 6.7e-07) and saturated (P = 3.2e-05) fatty acids; upregulated metabolites were enriched with lysophospholipids (P = 3.4e-4). Mendelian randomization analyses using genetic instruments for metabolites (N = 14,000) and MDD (N = 800,000) showed that genetically predicted higher levels of the lysophospholipid 1-linoleoyl-GPE (18:2) were associated with greater risk of depression. The identified metabolome-wide profile of depression indicated altered lipid metabolism with downregulation of long-chain fatty acids and upregulation of lysophospholipids, for which causal involvement was suggested using genetic tools. This metabolomics signature offers a window on depression pathophysiology and a potential access point for the development of novel therapeutic approaches.}, }
@article {pmid38792577, year = {2024}, author = {Koo, H and Morrow, CD}, title = {Bacteroidales-Specific Antimicrobial Genes Can Influence the Selection of the Dominant Fecal Strain of Bacteroides vulgatus and Bacteroides uniformis from the Gastrointestinal Tract Microbial Community.}, journal = {Life (Basel, Switzerland)}, volume = {14}, number = {5}, pages = {}, pmid = {38792577}, issn = {2075-1729}, abstract = {Bacteroides vulgatus and Bacteroides uniformis are known to be abundant in the human fecal microbial community. Although these strains typically remain stable over time in humans, disruption of this microbial community following antibiotics resulted in the transient change to new strains suggesting that a complex, dynamic strain community exists in humans. To further study the selection of dominant fecal microbial strains from the gastrointestinal tract (GIT) community, we analyzed three longitudinal metagenomic sequencing data sets using BLAST+ to identify genes encoding Bacteroidales-specific antimicrobial proteins (BSAP) that have known functions to restrict species-specific replication of B. uniformis (BSAP-2) or B. vulgatus (BSAP-3) and have been postulated to provide a competitive advantage in microbial communities. In the HMP (Human Microbiome Project) data set, we found fecal samples from individuals had B. vulgatus or B. uniformis with either complete or deleted BSAP genes that did not change over time. We also examined fecal samples from two separate longitudinal data sets of individuals who had been given either single or multiple antibiotics. The BSAP gene pattern from most individuals given either single or multiple antibiotics recovered to be the same as the pre-antibiotic strain. However, in a few individuals, we found incomplete BSAP-3 genes at early times during the recovery that were replaced by B. vulgatus with the complete BSAP-3 gene, consistent with the function of the BSAP to specifically restrict Bacteroides spp. The results of these studies provide insights into the fluxes that occur in the Bacteroides spp. GIT community following perturbation and the dynamics of the selection of a dominant fecal strain of Bacteroides spp.}, }
@article {pmid38765682, year = {2024}, author = {Chen, Z and Wang, Z and Ma, H and Bao, H and Jiang, T and Yang, T and Ma, S}, title = {Immune cells mediated the causal relationship between the gut microbiota and lung cancer: a Mendelian randomization study.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1390722}, pmid = {38765682}, issn = {1664-302X}, abstract = {INTRODUCTION: The gut microbiota (GM) influences the occurrence and progression of lung cancer (LC), with potential involvement of immune cells (IC). We aimed to investigate the causal impact of GM on LC and identify potential immune cell mediators.<br><br>METHODS: The utilized data for the Genome-Wide Association Studies (GWAS) were summarized as follows: gut microbiota data from the Dutch Microbiome Project (DMP) (N = 7,738), lung cancer data from the Transdisciplinary Research in Cancer of the Lung (TRICL) and International Lung Cancer Consortium (ILCCO) (Ncase = 29,266, Ncontrol = 56,450) included four types of cancer: NSCLC, LUAD, LUSC, and SCLC, and immune cell data from European populations (N = 3,757). We employed bi-directional two-sample univariable Mendelian randomization (UVMR), multivariable Mendelian randomization (MVMR), and mediation analysis to assess the causal relationship between GM and LC and potential immune cell mediators.<br><br>RESULTS: Bi-directional UVMR analysis revealed that 24 gut microbiota species can affect LC, while LC can affect the abundance of 17 gut microbiota species. Mediation analysis demonstrated that six immune cells mediated the causal relationships of seven gut microbiota species on LC: "CCR7 on naive CD8+ T cell" mediated the causal relationship between s_Alistipes_putredinis and LUAD, with a mediation proportion of 9.5% and P = 0.018; "IgD- CD27- B cell %lymphocyte" mediated the causal relationships between g_Gordonibacter and s_Gordonibacter_pamelaeae with LUSC, with mediation proportions of 11.8% and 11.9%, respectively and P = 0.029; "CD20- CD38- B cell %lymphocyte" mediated the causal relationship between s_Bacteroides_clarus and SCLC, with a mediation proportion of 13.8% and P = 0.005; "CD20 on IgD+ CD38- unswitched memory B cell" mediated the causal relationship between s_Streptococcus_thermophilus and SCLC, with a mediation proportion of 14.1% and P = 0.023; "HLA DR on CD14- CD16+ monocyte" mediated the causal relationship between s_Bifidobacterium_bifidum and SCLC, with a mediation proportion of 8.7% and P = 0.012; "CD45 on Granulocytic Myeloid-Derived Suppressor Cells" mediated the causal relationship between f_Lactobacillaceae and SCLC, with a mediation proportion of 4.0% and P = 0.021.<br><br>CONCLUSION: This Mendelian randomization study identified several specific gut microbiotas that exhibit causal relationships with lung cancer and potentially mediate immune cells.}, }
@article {pmid38745153, year = {2024}, author = {Liu, Y and Yu, J and Yang, Y and Han, B and Wang, Q and Du, S}, title = {Investigating the causal relationship of gut microbiota with GERD and BE: a bidirectional mendelian randomization.}, journal = {BMC genomics}, volume = {25}, number = {1}, pages = {471}, pmid = {38745153}, issn = {1471-2164}, support = {7204303//Beijing Natural Science Foundation/ ; 7204303//Beijing Natural Science Foundation/ ; 7204303//Beijing Natural Science Foundation/ ; 7204303//Beijing Natural Science Foundation/ ; 7204303//Beijing Natural Science Foundation/ ; 7204303//Beijing Natural Science Foundation/ ; }, mesh = {*Mendelian Randomization Analysis ; *Gastrointestinal Microbiome/genetics ; *Gastroesophageal Reflux/microbiology ; Humans ; *Barrett Esophagus/microbiology/genetics ; Risk Factors ; Polymorphism, Single Nucleotide ; }, abstract = {BACKGROUND: Gut microbiota(GM) have been proven associated with lots of gastrointestinal diseases, but its causal relationship with Gastroesophageal reflux disease(GERD) and Barrett's esophagus(BE) hasn't been explored. We aimed to uncover the causal relation between GM and GERD/BE and potential mediators by utilizing Mendelian Randomization(MR) analysis.<br><br>METHODS: Summary statistics of GM(comprising 301 bacteria taxa and 205 metabolism pathways) were extracted from MiBioGen Consortium(N&#x2009;=&#x2009;18,340) and Dutch Microbiome Project(N&#x2009;=&#x2009;7,738), GERD and BE from a multitrait meta-analysis(NGERD=602,604, NBE=56,429). Bidirectional two-sample MR analysis and linkage disequilibrium score regression(LDSC) were used to explore the genetic correlation between GM and GERD/BE. Mediation MR analysis was performed for the risk factors of GERD/BE, including Body mass index(BMI), weight, type 2 diabetes, major depressive disorder(MDD), smoking initiation, alcohol consumption, and dietary intake(including carbohydrate, sugar, fat, protein intake), to detect the potential mediators between GM and GERD/BE.<br><br>RESULTS: 11 bacterial taxa and 13 metabolism pathways were found associated with GERD, and 18 taxa and 5 pathways exhibited causal relationship with BE. Mediation MR analysis suggested weight and BMI played a crucial role in these relationships. LDSC identified 1 taxon and 4 metabolism pathways related to GERD, and 1 taxon related to BE. Specie Faecalibacterium prausnitzii had a suggestive impact on both GERD(OR&#x2009;=&#x2009;1.087, 95%CI&#x2009;=&#x2009;1.01-1.17) and BE(OR&#x2009;=&#x2009;1.388, 95%CI&#x2009;=&#x2009;1.03-1.86) and LDSC had determined their correlation. Reverse MR indicated that BE impacted 10 taxa and 4 pathways.<br><br>CONCLUSIONS: This study established a causal link between gut microbiota and GERD/BE, and identified the probable mediators. It offers new insights into the role of gut microbiota in the development and progression of GERD and BE in the host.}, }
@article {pmid38740275, year = {2024}, author = {Long, AR and Mortara, EL and Mendoza, BN and Fink, EC and Sacco, FX and Ciesla, MJ and Stack, TMM}, title = {Sequence similarity network analysis of drug- and dye-modifying azoreductase enzymes found in the human gut microbiome.}, journal = {Archives of biochemistry and biophysics}, volume = {757}, number = {}, pages = {110025}, pmid = {38740275}, issn = {1096-0384}, support = {P20 GM103430/GM/NIGMS NIH HHS/United States ; }, mesh = {Humans ; *Nitroreductases/metabolism/genetics ; *Gastrointestinal Microbiome ; *NADH, NADPH Oxidoreductases/metabolism/genetics/chemistry ; Coloring Agents/metabolism ; Molecular Docking Simulation ; Substrate Specificity ; Sulfasalazine ; Bacterial Proteins/metabolism/genetics/chemistry ; Kinetics ; Clostridiales/enzymology/genetics ; Azo Compounds/metabolism/chemistry ; }, abstract = {Drug metabolism by human gut microbes is often exemplified by azo bond reduction in the anticolitic prodrug sulfasalazine. Azoreductase activity is often found in incubations with cell cultures or ex vivo gut microbiome samples and contributes to the xenobiotic metabolism of drugs and food additives. Applying metagenomic studies to personalized medicine requires knowledge of the genes responsible for sulfasalazine and other drug metabolism, and candidate genes and proteins for drug modifications are understudied. A representative gut-abundant azoreductase from Anaerotignum lactatifermentan DSM 14214 efficiently reduces sulfasalazine and another drug, phenazopyridine, but could not reduce all azo-bonded drugs in this class. We used enzyme kinetics to characterize this enzyme for its NADH-dependent reduction of these drugs and food additives and performed computational docking to provide the groundwork for understanding substrate specificity in this family. We performed an analysis of the Flavodoxin-like fold InterPro family (IPR003680) by computing a sequence similarity network to classify distinct subgroups of the family and then performed chemically-guided functional profiling to identify proteins that are abundant in the NIH Human Microbiome Project dataset. This strategy aims to reduce the number of unique azoreductases needed to characterize one protein family in the diverse set of potential drug- and dye-modifying activities found in the human gut microbiome.}, }
@article {pmid38736244, year = {2024}, author = {Chen, J and Wang, X and Yang, J and Huang, J and Xie, M and Su, Z and Jiang, F}, title = {Association between gut microbiota and central retinal artery occlusion: A two-sample Mendelian randomization study.}, journal = {Indian journal of ophthalmology}, volume = {72}, number = {Suppl 5}, pages = {S801-S808}, pmid = {38736244}, issn = {1998-3689}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Mendelian Randomization Analysis ; *Retinal Artery Occlusion/diagnosis/microbiology/epidemiology ; *Genome-Wide Association Study ; Risk Factors ; Polymorphism, Single Nucleotide ; }, abstract = {PURPOSE: The gut microbiota might be closely related to central retinal artery occlusion (CRAO), but the causality has not been well defined. Two-sample Mendelian randomization (MR) study was used to reveal the potential causal effect between the gut microbiota and CRAO.<br><br>METHODS: Data for gut microbiota were obtained from the genome-wide association studies of the Dutch Microbiome Project (DMP) (n = 7738) and the MiBioGen consortium (n = 18,340), and data on CRAO were obtained from samples of FinnGen project (546 cases and 344,569 controls). Causalities of exposures and outcomes were explored mainly using the inverse variance weighted method. In addition, multiple sensitivity analyses including MR-Egger, weighted median (WM), simple mode, weighted mode, and MR Pleiotropy RESidual Sum and Outlier were simultaneously applied to validate the final results.<br><br>RESULTS: We identified three microbial pathways (two risk factors/one protective factor) and seven microbial taxa (two risk factors/five protective factors) associated with CRAO in the DMP study. Based on the data from the MiBioGen consortium, we identified seven microbial taxa (two risk factors/five protective factors) associated with CRAO, including the Eubacterium genus, which was consistently identified as a risk factor in both the DMP and the MiBioGen consortium MR analyses.<br><br>CONCLUSION: Our study implicates the potential causal effects of specific microbial taxa and pathways on CRAO, potentially providing new insights into the prevention and treatment of CRAO through specific gut microbial taxa and pathway. Since our conclusion is a hypothesis derived from secondary genome-wide association studies (GWAS) data analysis, further research is needed for confirmation.}, }
@article {pmid38720308, year = {2024}, author = {Zhou, J and Zhu, D and Xu, Y and Chen, C and Wang, K}, title = {Genetically predicted gut microbiota mediate the association between plasma lipidomics and primary sclerosing cholangitis.}, journal = {BMC gastroenterology}, volume = {24}, number = {1}, pages = {158}, pmid = {38720308}, issn = {1471-230X}, support = {No. JDY2023018//the Jiangsu University Medical Education Collaborative Innovation Fund Project/ ; No. Z2021010//the Medical Research Project of Jiangsu Health Commission/ ; }, mesh = {Humans ; *Cholangitis, Sclerosing/blood/microbiology/genetics ; *Gastrointestinal Microbiome/genetics ; *Lipidomics ; *Mendelian Randomization Analysis ; Male ; Genome-Wide Association Study ; Female ; Phosphatidylcholines/blood ; Dysbiosis/blood ; Middle Aged ; Adult ; }, abstract = {BACKGROUND: Primary sclerosing cholangitis (PSC) is a complex disease with pathogenic mechanisms that remain to be elucidated. Previous observational studies with small sample sizes have reported associations between PSC, dyslipidemia, and gut microbiota dysbiosis. However, the causality of these associations is uncertain, and there has been no systematic analysis to date.<br><br>METHODS: The datasets comprise data on PSC, 179 lipid species, and 412 gut microbiota species. PSC data (n&#x2009;=&#x2009;14,890) were sourced from the International PSC Study Group, while the dataset pertaining to plasma lipidomics originated from a study involving 7174 Finnish individuals. Data on gut microbiota species were derived from the Dutch Microbiome Project study, which conducted a genome-wide association study involving 7738 participants. Furthermore, we employed a two-step Mendelian randomization (MR) analysis to quantify the proportion of the effect of gut microbiota-mediated lipidomics on PSC.<br><br>RESULTS: Following a rigorous screening process, our MR analysis revealed a causal relationship between higher levels of gene-predicted Phosphatidylcholine (O-16:1_18:1) (PC O-16:1_18:1) and an increased risk of developing PSC (inverse variance-weighted method, odds ratio (OR) 1.30, 95% confidence interval (CI) 1.03-1.63). There is insufficient evidence to suggest that gene-predicted PSC impacts the levels of PC O-16:1_18:1 (OR 1.01, 95% CI 0.98-1.05). When incorporating gut microbiota data into the analysis, we found that Eubacterium rectale-mediated genetic prediction explains 17.59% of the variance in PC O-16:1_18:1 levels.<br><br>CONCLUSION: Our study revealed a causal association between PC O-16:1_18:1 levels and PSC, with a minor portion of the effect mediated by Eubacterium rectale. This study aims to further explore the pathogenesis of PSC and identify promising therapeutic targets. For patients with PSC who lack effective treatment options, the results are encouraging.}, }
@article {pmid38694799, year = {2024}, author = {Zhang, Y and Xue, G and Wang, F and Zhang, J and Xu, L and Yu, C}, title = {The impact of antibiotic exposure on antibiotic resistance gene dynamics in the gut microbiota of inflammatory bowel disease patients.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1382332}, pmid = {38694799}, issn = {1664-302X}, abstract = {BACKGROUND: While antibiotics are commonly used to treat inflammatory bowel disease (IBD), their widespread application can disturb the gut microbiota and foster the emergence and spread of antibiotic resistance. However, the dynamic changes to the human gut microbiota and direction of resistance gene transmission under antibiotic effects have not been clearly elucidated.<br><br>METHODS: Based on the Human Microbiome Project, a total of 90 fecal samples were collected from 30 IBD patients before, during and after antibiotic treatment. Through the analysis workflow of metagenomics, we described the dynamic process of changes in bacterial communities and resistance genes pre-treatment, during and post-treatment. We explored potential consistent relationships between gut microbiota and resistance genes, and established gene transmission networks among species before and after antibiotic use.<br><br>RESULTS: Exposure to antibiotics can induce alterations in the composition of the gut microbiota in IBD patients, particularly a reduction in probiotics, which gradually recovers to a new steady state after cessation of antibiotics. Network analyses revealed intra-phylum transfers of resistance genes, predominantly between taxonomically close organisms. Specific resistance genes showed increased prevalence and inter-species mobility after antibiotic cessation.<br><br>CONCLUSION: This study demonstrates that antibiotics shape the gut resistome through selective enrichment and promotion of horizontal gene transfer. The findings provide insights into ecological processes governing resistance gene dynamics and dissemination upon antibiotic perturbation of the microbiota. Optimizing antibiotic usage may help limit unintended consequences like increased resistance in gut bacteria during IBD management.}, }
@article {pmid38674735, year = {2024}, author = {Isokpehi, RD and Kim, Y and Krejci, SE and Trivedi, VD}, title = {Ecological Trait-Based Digital Categorization of Microbial Genomes for Denitrification Potential.}, journal = {Microorganisms}, volume = {12}, number = {4}, pages = {}, pmid = {38674735}, issn = {2076-2607}, support = {U41 HG006941/HG/NHGRI NIH HHS/United States ; U41HG006941/NH/NIH HHS/United States ; }, abstract = {Microorganisms encode proteins that function in the transformations of useful and harmful nitrogenous compounds in the global nitrogen cycle. The major transformations in the nitrogen cycle are nitrogen fixation, nitrification, denitrification, anaerobic ammonium oxidation, and ammonification. The focus of this report is the complex biogeochemical process of denitrification, which, in the complete form, consists of a series of four enzyme-catalyzed reduction reactions that transforms nitrate to nitrogen gas. Denitrification is a microbial strain-level ecological trait (characteristic), and denitrification potential (functional performance) can be inferred from trait rules that rely on the presence or absence of genes for denitrifying enzymes in microbial genomes. Despite the global significance of denitrification and associated large-scale genomic and scholarly data sources, there is lack of datasets and interactive computational tools for investigating microbial genomes according to denitrification trait rules. Therefore, our goal is to categorize archaeal and bacterial genomes by denitrification potential based on denitrification traits defined by rules of enzyme involvement in the denitrification reduction steps. We report the integration of datasets on genome, taxonomic lineage, ecosystem, and denitrifying enzymes to provide data investigations context for the denitrification potential of microbial strains. We constructed an ecosystem and taxonomic annotated denitrification potential dataset of 62,624 microbial genomes (866 archaea and 61,758 bacteria) that encode at least one of the twelve denitrifying enzymes in the four-step canonical denitrification pathway. Our four-digit binary-coding scheme categorized the microbial genomes to one of sixteen denitrification traits including complete denitrification traits assigned to 3280 genomes from 260 bacteria genera. The bacterial strains with complete denitrification potential pattern included Arcobacteraceae strains isolated or detected in diverse ecosystems including aquatic, human, plant, and Mollusca (shellfish). The dataset on microbial denitrification potential and associated interactive data investigations tools can serve as research resources for understanding the biochemical, molecular, and physiological aspects of microbial denitrification, among others. The microbial denitrification data resources produced in our research can also be useful for identifying microbial strains for synthetic denitrifying communities.}, }
@article {pmid38596649, year = {2024}, author = {Zhang, H and Ma, L and Peng, W and Wang, B and Sun, Y}, title = {Association between gut microbiota and onset of type 2 diabetes mellitus: a two-sample Mendelian randomization study.}, journal = {Frontiers in cellular and infection microbiology}, volume = {14}, number = {}, pages = {1327032}, pmid = {38596649}, issn = {2235-2988}, mesh = {Humans ; *Diabetes Mellitus, Type 2/genetics ; *Gastrointestinal Microbiome/genetics ; Genome-Wide Association Study ; Mendelian Randomization Analysis ; *Microbiota ; *Sulfalene ; Meta-Analysis as Topic ; }, abstract = {AIM: Mendelian randomization (MR) analysis has been used in the exploration of the role of gut microbiota (GM) in type 2 diabetes mellitus (T2DM); however, it was limited to the genus level. This study herein aims to investigate the relationship of GM, especially at the species level, with T2DM in order to provide some evidence for further exploration of more specific GM taxa and pathway abundance in T2DM.<br><br>METHODS: This two-sample MR study was based on the summary statistics of GM from the available genome-wide association study (GWAS) meta-analysis conducted by the MiBioGen consortium as well as the Dutch Microbiome Project (DMP), whereas the summary statistics of T2DM were obtained from the FinnGen consortium released data. Inverse variance weighted (IVW), MR-Egger, strength test (F), and weighted median methods were used to examine the causal association between GM and the onset of T2DM. Cochran's Q statistics was employed to quantify the heterogeneity of instrumental variables. Bonferroni's correction was conducted to correct the bias of multiple testing. We also performed reverse causality analysis.<br><br>RESULTS: The corrected IVW estimates suggested the increased relative abundance of family Oxalobacteraceae (OR = 1.0704) and genus Oxalobacter (OR = 1.0874), respectively, were associated with higher odds of T2DM, while that of species faecis (OR = 0.9460) had a negative relationship with T2DM. The relationships of class Betaproteobacteria, family Lactobacillaceae, species finegoldii, and species longum with T2DM were also significant according to the IVW results (all P < 0.05).<br><br>CONCLUSIONS: GM had a potential causal association with T2DM, especially species faecis, finegoldii, and longum. Further studies are still needed to clarify certain results that are contradictory with previous findings.}, }
@article {pmid38586050, year = {2024}, author = {Ho, PY and Huang, KC}, title = {Challenges in quantifying functional redundancy and selection in microbial communities.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2024.03.26.586891}, pmid = {38586050}, issn = {2692-8205}, abstract = {Microbiomes can exhibit large variations in species abundances but high reproducibility in abundances of functional units, an observation often considered evidence for functional redundancy. Based on such reduction in functional variability, selection is hypothesized to act on functional units in these ecosystems. However, the link between functional redundancy and selection remains unclear. Here, we show that reduction in functional variability does not always imply selection on functional profiles. We propose empirical null models to account for the confounding effects of statistical averaging and bias toward environment-independent beneficial functions. We apply our models to existing data sets, and find that the abundances of metabolic groups within microbial communities from bromeliad foliage do not exhibit any evidence of the previously hypothesized functional selection. By contrast, communities of soil bacteria or human gut commensals grown in vitro are selected for metabolic capabilities. By separating the effects of averaging and functional bias on functional variability, we find that the appearance of functional selection in gut microbiome samples from the Human Microbiome Project is artifactual, and that there is no evidence of selection for any molecular function represented by KEGG orthology. These concepts articulate a basic framework for quantifying functional redundancy and selection, advancing our understanding of the mapping between microbiome taxonomy and function.}, }
@article {pmid38577200, year = {2024}, author = {Salvadori, M and Rosso, G}, title = {Update on the gut microbiome in health and diseases.}, journal = {World journal of methodology}, volume = {14}, number = {1}, pages = {89196}, pmid = {38577200}, issn = {2222-0682}, abstract = {The Human Microbiome Project, Earth Microbiome Project, and next-generation sequencing have advanced novel genome association, host genetic linkages, and pathogen identification. The microbiome is the sum of the microbes, their genetic information, and their ecological niche. This study will describe how millions of bacteria in the gut affect the human body in health and disease. The gut microbiome changes in relation with age, with an increase in Bacteroidetes and Firmicutes. Host and environmental factors affecting the gut microbiome are diet, drugs, age, smoking, exercise, and host genetics. In addition, changes in the gut microbiome may affect the local gut immune system and systemic immune system. In this study, we discuss how the microbiome may affect the metabolism of healthy subjects or may affect the pathogenesis of metabolism-generating metabolic diseases. Due to the high number of publications on the argument, from a methodologically point of view, we decided to select the best papers published in referred journals in the last 3 years. Then we selected the previously published papers. The major goals of our study were to elucidate which microbiome and by which pathways are related to healthy and disease conditions.}, }
@article {pmid38563656, year = {2024}, author = {Zhu, J and Yin, J and Chen, J and Hu, M and Lu, W and Wang, H and Zhang, H and Chen, W}, title = {Integrative analysis with microbial modelling and machine learning uncovers potential alleviators for ulcerative colitis.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2336877}, pmid = {38563656}, issn = {1949-0984}, mesh = {Animals ; Mice ; Humans ; *Colitis, Ulcerative ; *Gastrointestinal Microbiome ; *Inflammatory Bowel Diseases ; *Colitis ; Machine Learning ; }, abstract = {Ulcerative colitis (UC) is a challenging form of inflammatory bowel disease, and its etiology is intricately linked to disturbances in the gut microbiome. To identify the potential alleviators of UC, we employed an integrative analysis combining microbial community modeling with advanced machine learning techniques. Using metagenomics data sourced from the Integrated Human Microbiome Project, we constructed individualized microbiome community models for each participant. Our analysis highlighted a significant decline in both α and β-diversity of strain-level microbial populations in UC subjects compared to controls. Distinct differences were also observed in the predicted fecal metabolite profiles and strain-to-metabolite contributions between the two groups. Using tree-based machine learning models, we successfully identified specific microbial strains and their associated metabolites as potential alleviators of UC. Notably, our experimental validation using a dextran sulfate sodium-induced UC mouse model demonstrated that the administration of Parabacteroides merdae ATCC 43,184 and N-acetyl-D-mannosamine provided notable relief from colitis symptoms. In summary, our study underscores the potential of an integrative approach to identify novel therapeutic avenues for UC, paving the way for future targeted interventions.}, }
@article {pmid38562901, year = {2024}, author = {Dilmore, AH and Kuplicki, R and McDonald, D and Kumar, M and Estaki, M and Youngblut, N and Tyakht, A and Ackermann, G and Blach, C and MahmoudianDehkordi, S and Dunlop, BW and Bhattacharyya, S and Guinjoan, S and Mandaviya, P and Ley, RE and Kaddaruh-Dauok, R and Paulus, MP and Knight, R and , }, title = {Medication Use is Associated with Distinct Microbial Features in Anxiety and Depression.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {38562901}, issn = {2692-8205}, support = {R01 AG046171/AG/NIA NIH HHS/United States ; U19 AG063744/AG/NIA NIH HHS/United States ; RF1 AG059093/AG/NIA NIH HHS/United States ; U01 AG061359/AG/NIA NIH HHS/United States ; RF1 AG057452/AG/NIA NIH HHS/United States ; RF1 AG058942/AG/NIA NIH HHS/United States ; RF1 AG051550/AG/NIA NIH HHS/United States ; }, abstract = {This study investigated the relationship between gut microbiota and neuropsychiatric disorders (NPDs), specifically anxiety disorder (ANXD) and/or major depressive disorder (MDD), as defined by DSM-IV or V criteria. The study also examined the influence of medication use, particularly antidepressants and/or anxiolytics, classified through the Anatomical Therapeutic Chemical (ATC) Classification System, on the gut microbiota. Both 16S rRNA gene amplicon sequencing and shallow shotgun sequencing were performed on DNA extracted from 666 fecal samples from the Tulsa-1000 and NeuroMAP CoBRE cohorts. The results highlight the significant influence of medication use; antidepressant use is associated with significant differences in gut microbiota beta diversity and has a larger effect size than NPD diagnosis. Next, specific microbes were associated with ANXD and MDD, highlighting their potential for non-pharmacological intervention. Finally, the study demonstrated the capability of Random Forest classifiers to predict diagnoses of NPD and medication use from microbial profiles, suggesting a promising direction for the use of gut microbiota as biomarkers for NPD. The findings suggest that future research on the gut microbiota's role in NPD and its interactions with pharmacological treatments are needed.}, }
@article {pmid38559015, year = {2024}, author = {Maghini, DG and Oduaran, OH and Wirbel, J and Olubayo, LAI and Smyth, N and Mathema, T and Belger, CW and Agongo, G and Boua, PR and Choma, SS and Gómez-Olivé, FX and Kisiangani, I and Mashaba, GR and Micklesfield, L and Mohamed, SF and Nonterah, EA and Norris, S and Sorgho, H and Tollman, S and Wafawanaka, F and Tluway, F and Ramsay, M and Bhatt, AS and Hazelhurst, S}, title = {Expanding the human gut microbiome atlas of Africa.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {38559015}, issn = {2692-8205}, support = {R01 AI148623/AI/NIAID NIH HHS/United States ; D43 TW010540/TW/FIC NIH HHS/United States ; R01 AI143757/AI/NIAID NIH HHS/United States ; U54 HG006938/HG/NHGRI NIH HHS/United States ; S10 OD023452/OD/NIH HHS/United States ; }, abstract = {Population studies are crucial in understanding the complex interplay between the gut microbiome and geographical, lifestyle, genetic, and environmental factors. However, populations from low- and middle-income countries, which represent ~84% of the world population, have been excluded from large-scale gut microbiome research. Here, we present the AWI-Gen 2 Microbiome Project, a cross-sectional gut microbiome study sampling 1,803 women from Burkina Faso, Ghana, Kenya, and South Africa. By intensively engaging with communities that range from rural and horticultural to urban informal settlements and post-industrial, we capture population diversity that represents a far greater breadth of the world's population. Using shotgun metagenomic sequencing, we find that study site explains substantially more microbial variation than disease status. We identify taxa with strong geographic and lifestyle associations, including loss of Treponema and Cryptobacteroides species and gain of Bifidobacterium species in urban populations. We uncover a wealth of prokaryotic and viral novelty, including 1,005 new bacterial metagenome-assembled genomes, and identify phylogeography signatures in Treponema succinifaciens. Finally, we find a microbiome signature of HIV infection that is defined by several taxa not previously associated with HIV, including Dysosmobacter welbionis and Enterocloster sp. This study represents the largest population-representative survey of gut metagenomes of African individuals to date, and paired with extensive clinical biomarkers, demographic data, and lifestyle information, provides extensive opportunity for microbiome-related discovery and research.}, }
@article {pmid38553666, year = {2024}, author = {Ma, ZS}, title = {Towards a unified medical microbiome ecology of the OMU for metagenomes and the OTU for microbes.}, journal = {BMC bioinformatics}, volume = {25}, number = {1}, pages = {137}, pmid = {38553666}, issn = {1471-2105}, mesh = {Animals ; Humans ; Metagenome ; *Microbiota/genetics ; *Gastrointestinal Microbiome ; Biodiversity ; Sequence Analysis, DNA ; Metagenomics/methods ; }, abstract = {BACKGROUND: Metagenomic sequencing technologies offered unprecedented opportunities and also challenges to microbiology and microbial ecology particularly. The technology has revolutionized the studies of microbes and enabled the high-profile human microbiome and earth microbiome projects. The terminology-change from microbes to microbiomes signals that our capability to count and classify microbes (microbiomes) has achieved the same or similar level as we can for the biomes (macrobiomes) of plants and animals (macrobes). While the traditional investigations of macrobiomes have usually been conducted through naturalists' (Linnaeus &amp; Darwin) naked eyes, and aerial and satellite images (remote-sensing), the large-scale investigations of microbiomes have been made possible by DNA-sequencing-based metagenomic technologies. Two major types of metagenomic sequencing technologies-amplicon sequencing and whole-genome (shotgun sequencing)-respectively generate two contrastingly different categories of metagenomic reads (data)-OTU (operational taxonomic unit) tables representing microorganisms and OMU (operational metagenomic unit), a new term coined in this article to represent various cluster units of metagenomic genes.<br><br>RESULTS: The ecological science of microbiomes based on the OTU representing microbes has been unified with the classic ecology of macrobes (macrobiomes), but the unification based on OMU representing metagenomes has been rather limited. In a previous series of studies, we have demonstrated the applications of several classic ecological theories (diversity, composition, heterogeneity, and biogeography) to the studies of metagenomes. Here I push the envelope for the unification of OTU and OMU again by demonstrating the applications of metacommunity assembly and ecological networks to the metagenomes of human gut microbiomes. Specifically, the neutral theory of biodiversity (Sloan's near neutral model), Ning et al.stochasticity framework, core-periphery network, high-salience skeleton network, special trio-motif, and positive-to-negative ratio are applied to analyze the OMU tables from whole-genome sequencing technologies, and demonstrated with seven human gut metagenome datasets from the human microbiome project.<br><br>CONCLUSIONS: All of the ecological theories demonstrated previously and in this article, including diversity, composition, heterogeneity, stochasticity, and complex network analyses, are equally applicable to OMU metagenomic analyses, just as to OTU analyses. Consequently, I strongly advocate the unification of OTU/OMU (microbiomes) with classic ecology of plants and animals (macrobiomes) in the context of medical ecology.}, }
@article {pmid38549112, year = {2024}, author = {Edwin, NR and Fitzpatrick, AH and Brennan, F and Abram, F and O'Sullivan, O}, title = {An in-depth evaluation of metagenomic classifiers for soil microbiomes.}, journal = {Environmental microbiome}, volume = {19}, number = {1}, pages = {19}, pmid = {38549112}, issn = {2524-6372}, support = {SFI/16/RC/3835//VistaMilk/ ; Ref: 2020019//Teagasc Walsh Scholarship Programme/ ; }, abstract = {BACKGROUND: Recent endeavours in metagenomics, exemplified by projects such as the human microbiome project and TARA Oceans, have illuminated the complexities of microbial biomes. A robust bioinformatic pipeline and meticulous evaluation of their methodology have contributed to the success of these projects. The soil environment, however, with its unique challenges, requires a specialized methodological exploration to maximize microbial insights. A notable limitation in soil microbiome studies is the dearth of soil-specific reference databases available to classifiers that emulate the complexity of soil communities. There is also a lack of in-vitro mock communities derived from soil strains that can be assessed for taxonomic classification accuracy.<br><br>RESULTS: In this study, we generated a custom in-silico mock community containing microbial genomes commonly observed in the soil microbiome. Using this mock community, we simulated shotgun sequencing data to evaluate the performance of three leading metagenomic classifiers: Kraken2 (supplemented with Bracken, using a custom database derived from GTDB-TK genomes along with its own default database), Kaiju, and MetaPhlAn, utilizing their respective default databases for a robust analysis. Our results highlight the importance of optimizing taxonomic classification parameters, database selection, as well as analysing trimmed reads and contigs. Our study showed that classifiers tailored to the specific taxa present in our samples led to fewer errors compared to broader databases including microbial eukaryotes, protozoa, or human genomes, highlighting the effectiveness of targeted taxonomic classification. Notably, an optimal classifier performance was achieved when applying a relative abundance threshold of 0.001% or 0.005%. The Kraken2 supplemented with bracken, with a custom database demonstrated superior precision, sensitivity, F1 score, and overall sequence classification. Using a custom database, this classifier classified 99% of in-silico reads and 58% of real-world soil shotgun reads, with the latter identifying previously overlooked phyla using a custom database.<br><br>CONCLUSION: This study underscores the potential advantages of in-silico methodological optimization in metagenomic analyses, especially when deciphering the complexities of soil microbiomes. We demonstrate that the choice of classifier and database significantly impacts microbial taxonomic profiling. Our findings suggest that employing Kraken2 with Bracken, coupled with a custom database of GTDB-TK genomes and fungal genomes at a relative abundance threshold of 0.001% provides optimal accuracy in soil shotgun metagenome analysis.}, }
@article {pmid38506069, year = {2024}, author = {Li, J and Zheng, G and Jiang, D and Deng, C and Zhang, Y and Ma, Y and Su, J}, title = {Mendelian randomization analysis reveals a causal effect of Streptococcus salivarius on diabetic retinopathy through regulating host fasting glucose.}, journal = {Journal of cellular and molecular medicine}, volume = {28}, number = {7}, pages = {e18200}, pmid = {38506069}, issn = {1582-4934}, support = {KYQD20201001//Scientific Research Foundation for Talents of Wenzhou Medical University/ ; LR19C060001//Natural Science Foundation of Zhejiang Province/ ; 2023M732679//China Postdoctoral Science Foundation/ ; 32200535//National Natural Science Foundation of China/ ; 61871294//National Natural Science Foundation of China/ ; 82172882//National Natural Science Foundation of China/ ; }, mesh = {Adult ; Humans ; Mendelian Randomization Analysis ; *Streptococcus salivarius ; *Diabetic Retinopathy ; Genome-Wide Association Study ; Fasting ; Glucose ; *Diabetes Mellitus ; }, abstract = {Diabetic retinopathy (DR) is one of leading causes of vision loss in adults with increasing prevalence worldwide. Increasing evidence has emphasized the importance of gut microbiome in the aetiology and development of DR. However, the causal relationship between gut microbes and DR remains largely unknown. To investigate the causal associations of DR with gut microbes and DR risk factors, we employed two-sample Mendelian Randomization (MR) analyses to estimate the causal effects of 207 gut microbes on DR outcomes. Inputs for MR included Genome-wide Association Study (GWAS) summary statistics of 207 taxa of gut microbes (the Dutch Microbiome Project) and 21 risk factors for DR. The GWAS summary statistics data of DR was from the FinnGen Research Project. Data analysis was performed in May 2023. We identified eight bacterial taxa that exhibited significant causal associations with DR (FDR < 0.05). Among them, genus Collinsella and species Collinsella aerofaciens were associated with increased risk of DR, while the species Bacteroides faecis, Burkholderiales bacterium_1_1_47, Ruminococcus torques, Streptococcus salivarius, genus Burkholderiales_noname and family Burkholderiales_noname showed protective effects against DR. Notably, we found that the causal effect of species Streptococcus salivarius on DR was mediated through the level of host fasting glucose, a well-established risk factor for DR. Our results reveal that specific gut microbes may be causally linked to DR via mediating host metabolic risk factors, highlighting potential novel therapeutic or preventive targets for DR.}, }
@article {pmid38497260, year = {2024}, author = {Singh, A and Luallen, RJ}, title = {Understanding the factors regulating host-microbiome interactions using Caenorhabditis elegans.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {379}, number = {1901}, pages = {20230059}, pmid = {38497260}, issn = {1471-2970}, support = {R35 GM146836/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Humans ; Caenorhabditis elegans/genetics ; *Microbiota ; *Gastrointestinal Microbiome ; }, abstract = {The Human Microbiome Project was a research programme that successfully identified associations between microbial species and healthy or diseased individuals. However, a major challenge identified was the absence of model systems for studying host-microbiome interactions, which would increase our capacity to uncover molecular interactions, understand organ-specificity and discover new microbiome-altering health interventions. Caenorhabditis elegans has been a pioneering model organism for over 70 years but was largely studied in the absence of a microbiome. Recently, ecological sampling of wild nematodes has uncovered a large amount of natural genetic diversity as well as a slew of associated microbiota. The field has now explored the interactions of C. elegans with its associated gut microbiome, a defined and non-random microbial community, highlighting its suitability for dissecting host-microbiome interactions. This core microbiome is being used to study the impact of host genetics, age and stressors on microbiome composition. Furthermore, single microbiome species are being used to dissect molecular interactions between microbes and the animal gut. Being amenable to health altering genetic and non-genetic interventions, C. elegans has emerged as a promising system to generate and test new hypotheses regarding host-microbiome interactions, with the potential to uncover novel paradigms relevant to other systems. This article is part of the theme issue 'Sculpting the microbiome: how host factors determine and respond to microbial colonization'.}, }
@article {pmid38491556, year = {2024}, author = {Elradi, M and Ahmed, AI and Saleh, AM and Abdel-Raouf, KMA and Berika, L and Daoud, Y and Amleh, A}, title = {Derivation of a novel antimicrobial peptide from the Red Sea Brine Pools modified to enhance its anticancer activity against U2OS cells.}, journal = {BMC biotechnology}, volume = {24}, number = {1}, pages = {14}, pmid = {38491556}, issn = {1472-6750}, mesh = {Animals ; Mice ; Humans ; Caspase 3/genetics/metabolism/pharmacology ; Survivin/genetics/metabolism/pharmacology ; Escherichia coli/metabolism ; Antimicrobial Peptides ; Cell Line, Tumor ; Indian Ocean ; Ki-67 Antigen/metabolism ; Staphylococcus aureus ; Apoptosis ; Peptides/pharmacology/metabolism ; *Antineoplastic Agents/pharmacology/chemistry ; *Anti-Infective Agents/pharmacology ; Annexins/pharmacology ; *Salts ; }, abstract = {Cancer associated drug resistance is a major cause for cancer aggravation, particularly as conventional therapies have presented limited efficiency, low specificity, resulting in long term deleterious side effects. Peptide based drugs have emerged as potential alternative cancer treatment tools due to their selectivity, ease of design and synthesis, safety profile, and low cost of manufacturing. In this study, we utilized the Red Sea metagenomics database, generated during AUC/KAUST Red Sea microbiome project, to derive a viable anticancer peptide (ACP). We generated a set of peptide hits from our library that shared similar composition to ACPs. A peptide with a homeodomain was selected, modified to improve its anticancer properties, verified to maintain high anticancer properties, and processed for further in-silico prediction of structure and function. The peptide's anticancer properties were then assessed in vitro on osteosarcoma U2OS cells, through cytotoxicity assay (MTT assay), scratch-wound healing assay, apoptosis/necrosis detection assay (Annexin/PI assay), RNA expression analysis of Caspase 3, KI67 and Survivin, and protein expression of PARP1. L929 mouse fibroblasts were also assessed for cytotoxicity treatment. In addition, the antimicrobial activity of the peptide was also examined on E coli and S. aureus, as sample representative species of the human bacterial microbiome, by examining viability, disk diffusion, morphological assessment, and hemolytic analysis. We observed a dose dependent cytotoxic response from peptide treatment of U2OS, with a higher tolerance in L929s. Wound closure was debilitated in cells exposed to the peptide, while annexin fluorescent imaging suggested peptide treatment caused apoptosis as a major mode of cell death. Caspase 3 gene expression was not altered, while KI67 and Survivin were both downregulated in peptide treated cells. Additionally, PARP-1 protein analysis showed a decrease in expression with peptide exposure. The peptide exhibited minimal antimicrobial activity on critical human microbiome species E. coli and S. aureus, with a low inhibition rate, maintenance of structural morphology and minimal hemolytic impact. These findings suggest our novel peptide displayed preliminary ACP properties against U2OS cells, through limited specificity, while triggering apoptosis as a primary mode of cell death and while having minimal impact on the microbiological species E. coli and S. aureus.}, }
@article {pmid38486697, year = {2024}, author = {Xiao, QA and Qin, L and Yu, J and Hu, YT and Ai, LF and Wang, DC and Xia, X and Zhang, XL}, title = {The causality between gut microbiome and chronic regional pain: a Mendelian randomization analysis.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1329521}, pmid = {38486697}, issn = {1664-302X}, abstract = {BACKGROUND: Numerous investigations have underscored the causal effect between chronic pain (CP) and gut microbiota, jointly contributing to the onset and development of widespread CP. Nonetheless, there was still uncertainty about the causal effect between gut microbiota and chronic regional pain (CRP).<br><br>METHODS: Genome-wide association study (GWAS) summary data of gut microbial taxa (MiBioGen Consortium: 211 microbiotas and the Dutch Microbiome Project: 207 microbiotas) and eight types of CRP were used to reveal the causal effect between persistent pain in a specific region of the body and gut microbiota. A two-sample bidirectional Mendelian randomization (MR) design was used. In order to ensure the accuracy of the results, multiple sensitivity analyses were employed.<br><br>RESULTS: This study uncovered significant causal associations between six gut microbial taxa and three types of CRP (forward: Genus Parabacteroides for general pain; Class Bacteroidia, Order Bacteroidales, and Phylum Bacteroidetes for back pain. Reverse: knee pain for Genus Howardella and Order Coriobacteriales) by forward and reverse MR analysis. These findings had been verified by a rigorous Bonferroni correction. Furthermore, this research identified 19 microbial taxa that exhibited potential correlations with four types of CRP. There are no significant or potential gut microbiotas that were associated with other types of CRP, including fascial pain, stomach or abdominal pain, and hip pain.<br><br>CONCLUSION: This two-sample bidirectional MR analysis unveiled the causality between gut microbial taxa and eight CRP conditions. The findings reveal the interplay between CRP and 6 gut microbiotas while also delineating 19 potential specific microbial taxa corresponding to diverse locations of persistent pain.}, }
@article {pmid38481313, year = {2024}, author = {Wang, J and Teng, M and Feng, R and Su, X and Xu, K and Wang, J and Wang, G and Zhang, Y and Xu, P}, title = {Large-scale causal analysis of gut microbiota and six common complications of diabetes: a mendelian randomization study.}, journal = {Diabetology &amp; metabolic syndrome}, volume = {16}, number = {1}, pages = {66}, pmid = {38481313}, issn = {1758-5996}, abstract = {BACKGROUND: This study aimed to reveal the association between the gut microbiota (GM) and six diabetic complications: diabetic hypoglycemia; ketoacidosis; nephropathy; neuropathy; retinopathy; and Charcot's foot.<br><br>METHODS: GM data were obtained from the MiBioGen consortium and Dutch Microbiome Project while data on the six diabetic complications were obtained from the FinnGen consortium. Two-sample Mendelian randomization (TSMR) was performed to explore the association between GM and the common diabetic complications. Inverse MR analysis was conducted to examine the effect of diabetic complications on the identified GM. Sensitivity tests were conducted to validate the stability of the results. Finally, multivariate MR (MVMR) was performed to determine whether GM had a direct influence on the diabetic complications.<br><br>RESULTS: After multiple corrections, the inverse variance weighted (IVW) results predicted 61 suggestive markers between GM and six diabetic complications. In particular, the IVW results revealed that the Bacteroidia class and Bacteroidales order were positively associated with diabetic hypoglycemia while the Verrucomicrobiae class and Verrucomicrobiales order were positively associated with diabetic nephropathy. Based on the replication analysis, these results were identified to be stable. MVMR showed that the results remained stable after accounting for traditional risk factors.<br><br>CONCLUSION: Extensive causal associations were found between GM and diabetic complications, which may provide new insights into the mechanisms of microbiome-mediated complications of diabetes.}, }
@article {pmid38474213, year = {2024}, author = {Hong, BY and Driscoll, M and Gratalo, D and Jarvie, T and Weinstock, GM}, title = {Improved DNA Extraction and Amplification Strategy for 16S rRNA Gene Amplicon-Based Microbiome Studies.}, journal = {International journal of molecular sciences}, volume = {25}, number = {5}, pages = {}, pmid = {38474213}, issn = {1422-0067}, mesh = {Humans ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA/methods ; Genes, rRNA ; Reproducibility of Results ; DNA, Bacterial/genetics ; *Microbiota/genetics ; Bacteria/genetics ; High-Throughput Nucleotide Sequencing/methods ; }, abstract = {Next-generation sequencing technology has driven the rapid advancement of human microbiome studies by enabling community-level sequence profiling of microbiomes. Although all microbiome sequencing methods depend on recovering the DNA from a sample as a first critical step, lysis methods can be a major determinant of microbiome profile bias. Gentle enzyme-based DNA preparation methods preserve DNA quality but can bias the results by failing to open difficult-to-lyse bacteria. Mechanical methods like bead beating can also bias DNA recovery because the mechanical energy required to break tougher cell walls may shear the DNA of the more easily lysed microbes, and shearing can vary depending on the time and intensity of beating, influencing reproducibility. We introduce a non-mechanical, non-enzymatic, novel rapid microbial DNA extraction procedure suitable for 16S rRNA gene-based microbiome profiling applications that eliminates bead beating. The simultaneous application of alkaline, heat, and detergent ('Rapid' protocol) to milligram quantity samples provided consistent representation across the population of difficult and easily lysed bacteria equal to or better than existing protocols, producing sufficient high-quality DNA for full-length 16S rRNA gene PCR. The novel 'Rapid' method was evaluated using mock bacterial communities containing both difficult and easily lysed bacteria. Human fecal sample testing compared the novel Rapid method with a standard Human Microbiome Project (HMP) protocol for samples from lung cancer patients and controls. DNA recovered from both methods was analyzed using 16S rRNA gene sequencing of the V1V3 and V4 regions on the Illumina platform and the V1V9 region on the PacBio platform. Our findings indicate that the 'Rapid' protocol consistently yielded higher levels of Firmicutes species, which reflected the profile of the bacterial community structure more accurately, which was confirmed by mock community evaluation. The novel 'Rapid' DNA lysis protocol reduces population bias common to bead beating and enzymatic lysis methods, presenting opportunities for improved microbial community profiling, combined with the reduction in sample input to 10 milligrams or less, and it enables rapid transfer and simultaneous lysis of 96 samples in a standard plate format. This results in a 20-fold reduction in sample handling time and an overall 2-fold time advantage when compared to widely used commercial methods. We conclude that the novel 'Rapid' DNA extraction protocol offers a reliable alternative for preparing fecal specimens for 16S rRNA gene amplicon sequencing.}, }
@article {pmid38467837, year = {2024}, author = {Bhosle, A and Bae, S and Zhang, Y and Chun, E and Avila-Pacheco, J and Geistlinger, L and Pishchany, G and Glickman, JN and Michaud, M and Waldron, L and Clish, CB and Xavier, RJ and Vlamakis, H and Franzosa, EA and Garrett, WS and Huttenhower, C}, title = {Integrated annotation prioritizes metabolites with bioactivity in inflammatory bowel disease.}, journal = {Molecular systems biology}, volume = {20}, number = {4}, pages = {338-361}, pmid = {38467837}, issn = {1744-4292}, support = {P30 DK040561/DK/NIDDK NIH HHS/United States ; P30 DK043351/DK/NIDDK NIH HHS/United States ; R01 CA230551/CA/NCI NIH HHS/United States ; R24 DK110499/DK/NIDDK NIH HHS/United States ; }, mesh = {Humans ; Animals ; Mice ; *Inflammatory Bowel Diseases/drug therapy/metabolism ; *Colitis ; Metabolome ; Bile Acids and Salts ; }, abstract = {Microbial biochemistry is central to the pathophysiology of inflammatory bowel diseases (IBD). Improved knowledge of microbial metabolites and their immunomodulatory roles is thus necessary for diagnosis and management. Here, we systematically analyzed the chemical, ecological, and epidemiological properties of ~82k metabolic features in 546 Integrative Human Microbiome Project (iHMP/HMP2) metabolomes, using a newly developed methodology for bioactive compound prioritization from microbial communities. This suggested >1000 metabolic features as potentially bioactive in IBD and associated ~43% of prevalent, unannotated features with at least one well-characterized metabolite, thereby providing initial information for further characterization of a significant portion of the fecal metabolome. Prioritized features included known IBD-linked chemical families such as bile acids and short-chain fatty acids, and less-explored bilirubin, polyamine, and vitamin derivatives, and other microbial products. One of these, nicotinamide riboside, reduced colitis scores in DSS-treated mice. The method, MACARRoN, is generalizable with the potential to improve microbial community characterization and provide therapeutic candidates.}, }
@article {pmid38340164, year = {2024}, author = {Osborne, C and Gilbert-Parkes, S and Spiers, G and Lamit, LJ and Lilleskov, EA and Basiliko, N and Watmough, S and , }, title = {Global Patterns of Metal and Other Element Enrichment in Bog and Fen Peatlands.}, journal = {Archives of environmental contamination and toxicology}, volume = {86}, number = {2}, pages = {125-139}, pmid = {38340164}, issn = {1432-0703}, mesh = {Wetlands ; Metals ; *Mercury/analysis ; Soil ; *Environmental Pollutants ; }, abstract = {Peatlands are found on all continents, covering 3% of the global land area. However, the spatial extent and causes of metal enrichment in peatlands is understudied and no attempt has been made to evaluate global patterns of metal enrichment in bog and fen peatlands, despite that certain metals and rare earth elements (REE) arise from anthropogenic sources. We analyzed 368 peat cores sampled in 16 countries across five continents and measured metal and other element concentrations at three depths down to 70 cm as well as estimated cumulative atmospheric S deposition (1850-2009) for each site. Sites were assigned to one of three distinct broadly recognized peatland categories (bog, poor fen, and intermediate-to-moderately rich fen) that varied primarily along a pH gradient. Metal concentrations differed among peatland types, with intermediate-to-moderately rich fens demonstrating the highest concentrations of most metals. Median enrichment factors (EFs; a metric comparing natural and anthropogenic metal deposition) for individual metals were similar among bogs and fens (all groups), with metals likely to be influenced by anthropogenic sources (As, Cd, Co, Cu, Hg, Pb, and Sb) demonstrating median enrichment factors (EFs) > 1.5. Additionally, mean EFs were substantially higher than median values, and the positive correlation (< 0.40) with estimated cumulative atmospheric S deposition, confirmed some level of anthropogenic influence of all pollutant metals except for Hg that was unrelated to S deposition. Contrary to expectations, high EFs were not restricted to pollutant metals, with Mn, K and Rb all exhibiting elevated median EFs that were in the same range as pollutant metals likely due to peatland biogeochemical processes leading to enrichment of these nutrients in surface soil horizons. The global patterns of metal enrichment in bogs and fens identified in this study underscore the importance of these peatlands as environmental archives of metal deposition, but also illustrates that biogeochemical processes can enrich metals in surface peat and EFs alone do not necessarily indicate atmospheric contamination.}, }
@article {pmid38285276, year = {2024}, author = {Fang, M and Liu, W and Wang, Z and Li, J and Hu, S and Li, Z and Chen, W and Zhang, N}, title = {Causal associations between gut microbiota with intervertebral disk degeneration, low back pain, and sciatica: a Mendelian randomization study.}, journal = {European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society}, volume = {33}, number = {4}, pages = {1424-1439}, pmid = {38285276}, issn = {1432-0932}, support = {81972514//National Natural Science Foundation of China/ ; }, mesh = {Humans ; *Sciatica/epidemiology/genetics ; *Intervertebral Disc Degeneration/epidemiology/genetics ; *Low Back Pain/epidemiology/genetics ; *Gastrointestinal Microbiome/genetics ; Mendelian Randomization Analysis ; Genome-Wide Association Study ; *Intervertebral Disc Displacement ; }, abstract = {PURPOSE: Although studies have suggested that gut microbiota may be associated with intervertebral disk disease, their causal relationship is unclear. This study aimed to investigate the causal relationship between the gut microbiota and its metabolic pathways with the risk of intervertebral disk degeneration (IVDD), low back pain (LBP), and sciatica.<br><br>METHODS: Genetic variation data for 211 gut microbiota taxa at the phylum to genus level were obtained from the MiBioGen consortium. Genetic variation data for 105 taxa at the species level and 205 metabolic pathways were obtained from the Dutch Microbiome Project. Genetic variation data for disease outcomes were obtained from the FinnGen consortium. The causal relationships between the gut microbiota and its metabolic pathways and the risk of IVDD, LBP, and sciatica were evaluated via Mendelian randomization (MR). The robustness of the results was assessed through sensitivity analysis.<br><br>RESULTS: Inverse variance weighting identified 46 taxa and 33 metabolic pathways that were causally related to IVDD, LBP, and sciatica. After correction by weighted median and MR-PRESSO, 15 taxa and nine pathways remained stable. After FDR correction, only the effect of the genus_Eubacterium coprostanoligenes group on IVDD remained stable. Sensitivity analyses showed no evidence of horizontal pleiotropy, heterogeneity, or reverse causation.<br><br>CONCLUSION: Some microbial taxa and their metabolic pathways are causally related to IVDD, LBP, and sciatica and may serve as potential intervention targets. This study provides new insights into the mechanisms of gut microbiota-mediated development of intervertebral disk disease.}, }
@article {pmid38284649, year = {2024}, author = {Hayer, SS and Conrin, M and French, JA and Benson, AK and Alvarez, S and Cooper, K and Fischer, A and Alsafwani, ZW and Gasper, W and Suhr Van Haute, MJ and Hassenstab, HR and Azadmanesh, S and Briardy, M and Gerbers, S and Jabenis, A and Thompson, JL and Clayton, JB}, title = {Antibiotic-induced gut dysbiosis elicits gut-brain axis relevant multi-omic signatures and behavioral and neuroendocrine changes in a nonhuman primate model.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2305476}, pmid = {38284649}, issn = {1949-0984}, support = {K01 OD030514/OD/NIH HHS/United States ; P20 GM103427/GM/NIGMS NIH HHS/United States ; P30 CA036727/CA/NCI NIH HHS/United States ; R25 GM141506/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Humans ; *Anti-Bacterial Agents/toxicity ; Callithrix ; Brain-Gut Axis ; *Gastrointestinal Microbiome ; Dysbiosis/microbiology ; Multiomics ; }, abstract = {Emerging evidence indicates that antibiotic-induced dysbiosis can play an etiological role in the pathogenesis of neuropsychiatric disorders. However, most of this evidence comes from rodent models. The objective of this study was to evaluate if antibiotic-induced gut dysbiosis can elicit changes in gut metabolites and behavior indicative of gut-brain axis disruption in common marmosets (Callithrix jacchus) - a nonhuman primate model often used to study sociability and stress. We were able to successfully induce dysbiosis in marmosets using a custom antibiotic cocktail (vancomycin, enrofloxacin and neomycin) administered orally for 28 days. This gut dysbiosis altered gut metabolite profiles, behavior, and stress reactivity. Increase in gut Fusobacterium spp. post-antibiotic administration was a novel dysbiotic response and has not been observed in any rodent or human studies to date. There were significant changes in concentrations of several gut metabolites which are either neurotransmitters (e.g., GABA and serotonin) or have been found to be moderators of gut-brain axis communication in rodent models (e.g., short-chain fatty acids and bile acids). There was an increase in affiliative behavior and sociability in antibiotic-administered marmosets, which might be a coping mechanism in response to gut dysbiosis-induced stress. Increase in urinary cortisol levels after multiple stressors provides more definitive proof that this model of dysbiosis may cause disrupted communication between gut and brain in common marmosets. This study is a first attempt to establish common marmosets as a novel model to study the impact of severe gut dysbiosis on gut-brain axis cross-talk and behavior.}, }
@article {pmid38233502, year = {2024}, author = {Chopra, A and Franco-Duarte, R and Rajagopal, A and Choowong, P and Soares, P and Rito, T and Eberhard, J and Jayasinghe, TN}, title = {Exploring the presence of oral bacteria in non-oral sites of patients with cardiovascular diseases using whole metagenomic data.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {1476}, pmid = {38233502}, issn = {2045-2322}, support = {2022.00340.CEECIND//Funda&#xe7;&#xe3;o para a Ci&#xea;ncia e a Tecnologia/ ; "Contrato-Programa" UIDB/04050/2020//Funda&#xe7;&#xe3;o para a Ci&#xea;ncia e a Tecnologia/ ; }, mesh = {Humans ; *Cardiovascular Diseases ; *Microbiota/genetics ; Bacteria/genetics ; Metagenome ; *Plaque, Atherosclerotic ; }, abstract = {Cardiovascular diseases (CVDs) encompass various conditions affecting the heart and its blood vessels and are often linked with oral microbes. Our data analysis aimed to identify oral bacteria from other non-oral sites (i.e., gut, arterial plaque and cultured blood) that could be linked with CVDs. Taxonomic profiling identified bacteria to the species level and compared with the Human Oral Microbiome Database (HOMD). The oral bacteria in the gut, cultured blood and arterial plaque samples were catalogued, with their average frequency calculated for each sample. Additionally, data were filtered by comparison with the Human Microbiome Project (HMP) database. We identified 17,243 microbial species, of which 410 were present in the HOMD database and further denominated as "oral", and were found in at least one gut sample, but only 221 and 169 species were identified in the cultured blood and plaque samples, respectively. Of the 410 species, 153 were present solely in oral-associated environments after comparison with the HMP database, irrespective of their presence in other body sites. Our results suggest a potential connection between the presence of specific species of oral bacterial and occurrence of CVDs. Detecting these oral bacterial species in non-oral sites of patients with CVDs could help uncover the link between oral health and general health, including cardiovascular conditions via bacterial translocation.}, }
@article {pmid38168274, year = {2023}, author = {Liu, R and Wang, Y and Cheng, D}, title = {Micro-DeMix: A mixture beta-multinomial model for investigating the fecal microbiome compositions.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {38168274}, issn = {2692-8205}, support = {R01 GM145772/GM/NIGMS NIH HHS/United States ; }, abstract = {Extensive research has uncovered the involvement of the human gut microbiome in various facets of human health, including metabolism, nutrition, physiology, and immune function. Researchers often study fecal microbiota as a proxy for understanding the gut microbiome. However, it has been demonstrated that this approach may not suffice to yield a comprehensive understanding of the entire gut microbial community. Emerging research is revealing the heterogeneity of the gut microbiome across different gastrointestinal (GI) locations in both composition and functions. While spatial metagenomics approach has been developed to address these variations in mice, limitations arise when applying it to human-subject research, primarily due to its invasive nature. With these restrictions, we introduce Micro-DeMix, a mixture beta-multinomial model that decomposes the fecal microbiome at compositional level to understand the heterogeneity of the gut microbiome across various GI locations and extract meaningful insights about the biodiversity of the gut microbiome. Moreover, Micro-DeMix facilitates the discovery of differentially abundant microbes between GI regions through a hypothesis testing framework. We utilize the Inflammatory Bowel Disease (IBD) data from the NIH Integrative Human Microbiome Project to demonstrate the effectiveness and efficiency of the proposed Micro-DeMix.}, }
@article {pmid38132705, year = {2024}, author = {Hoisington, AJ and Stearns-Yoder, KA and Stamper, CE and Holliday, R and Brostow, DP and Penzenik, ME and Forster, JE and Postolache, TT and Lowry, CA and Brenner, LA}, title = {Association of homelessness and diet on the gut microbiome: a United States-Veteran Microbiome Project (US-VMP) study.}, journal = {mSystems}, volume = {9}, number = {1}, pages = {e0102123}, pmid = {38132705}, issn = {2379-5077}, mesh = {Humans ; United States/epidemiology ; *Veterans/psychology ; *Gastrointestinal Microbiome ; *Ill-Housed Persons ; *Microbiota ; Diet ; }, abstract = {Military veterans account for 8% of homeless individuals living in the United States. To highlight associations between history of homelessness and the gut microbiome, we compared the gut microbiome of veterans who reported having a previous experience of homelessness to those from individuals who reported never having experienced a period of homelessness. Moreover, we examined the impact of the cumulative exposure of prior and current homelessness to understand possible associations between these experiences and the gut microbiome. Microbiome samples underwent genomic sequencing and were analyzed based on alpha diversity, beta diversity, and taxonomic differences. Additionally, demographic information, dietary data, and mental health history were collected. A lifetime history of homelessness was found to be associated with alcohol use disorder, substance use disorder, and healthy eating index compared to those without such a history. In terms of differences in gut microbiota, beta diversity was significantly different between veterans who had experienced homelessness and veterans who had never been homeless (P = 0.047, weighted UniFrac), while alpha diversity was similar. The microbial community differences were, in part, driven by a lower relative abundance of Akkermansia in veterans who had experienced homelessness (mean; range [in percentages], 1.07; 0-33.9) compared to veterans who had never been homeless (2.02; 0-36.8) (P = 0.014, ancom-bc2). Additional research is required to facilitate understanding regarding the complex associations between homelessness, the gut microbiome, and mental and physical health conditions, with a focus on increasing understanding regarding the longitudinal impact of housing instability throughout the lifespan.IMPORTANCEAlthough there are known stressors related to homelessness as well as chronic health conditions experienced by those without stable housing, there has been limited work evaluating the associations between microbial community composition and homelessness. We analyzed, for the first time, bacterial gut microbiome associations among those with experiences of homelessness on alpha diversity, beta diversity, and taxonomic differences. Additionally, we characterized the influences of diet, demographic characteristics, military service history, and mental health conditions on the microbiome of veterans with and without any lifetime history of homelessness. Future longitudinal research to evaluate the complex relationships between homelessness, the gut microbiome, and mental health outcomes is recommended. Ultimately, differences in the gut microbiome of individuals experiencing and not experiencing homelessness could assist in identification of treatment targets to improve health outcomes.}, }
@article {pmid38127919, year = {2023}, author = {L'Heureux, JE and van der Giezen, M and Winyard, PG and Jones, AM and Vanhatalo, A}, title = {Localisation of nitrate-reducing and highly abundant microbial communities in the oral cavity.}, journal = {PloS one}, volume = {18}, number = {12}, pages = {e0295058}, pmid = {38127919}, issn = {1932-6203}, mesh = {Humans ; *Nitrates/metabolism ; Nitrogen Dioxide ; Mouth/microbiology ; Bacteria ; Saliva/metabolism ; *Microbiota ; Streptococcus ; }, abstract = {The nitrate (NO3-) reducing bacteria resident in the oral cavity have been implicated as key mediators of nitric oxide (NO) homeostasis and human health. NO3--reducing oral bacteria reduce inorganic dietary NO3- to nitrite (NO2-) via the NO3--NO2--NO pathway. Studies of oral NO3--reducing bacteria have typically sampled from either the tongue surface or saliva. The aim of this study was to assess whether other areas in the mouth could contain a physiologically relevant abundance of NO3- reducing bacteria, which may be important for sampling in clinical studies. The bacterial composition of seven oral sample types from 300 individuals were compared using a meta-analysis of the Human Microbiome Project data. This analysis revealed significant differences in the proportions of 20 well-established oral bacteria and highly abundant NO3--reducing bacteria across each oral site. The genera included Actinomyces, Brevibacillus, Campylobacter, Capnocytophaga, Corynebacterium, Eikenella, Fusobacterium, Granulicatella, Haemophilus, Leptotrichia, Microbacterium, Neisseria, Porphyromonas, Prevotella, Propionibacterium, Rothia, Selenomonas, Staphylococcus, Streptococcus and Veillonella. The highest proportion of NO3--reducing bacteria was observed in saliva, where eight of the bacterial genera were found in higher proportion than on the tongue dorsum, whilst the lowest proportions were found in the hard oral surfaces. Saliva also demonstrated higher intra-individual variability and bacterial diversity. This study provides new information on where samples should be taken in the oral cavity to assess the abundance of NO3--reducing bacteria. Taking saliva samples may benefit physiological studies, as saliva contained the highest abundance of NO3- reducing bacteria and is less invasive than other sampling methods. These results inform future studies coupling oral NO3--reducing bacteria research with physiological outcomes affecting human health.}, }
@article {pmid38095449, year = {2024}, author = {Arehart, CH and Sterrett, JD and Garris, RL and Quispe-Pilco, RE and Gignoux, CR and Evans, LM and Stanislawski, MA}, title = {Poly-omic risk scores predict inflammatory bowel disease diagnosis.}, journal = {mSystems}, volume = {9}, number = {1}, pages = {e0067723}, pmid = {38095449}, issn = {2379-5077}, support = {K01 HL157658/HL/NHLBI NIH HHS/United States ; P30 DK048520/DK/NIDDK NIH HHS/United States ; T32 MH016880/MH/NIMH NIH HHS/United States ; }, mesh = {Humans ; *Inflammatory Bowel Diseases/diagnosis ; Metagenomics/methods ; Phenotype ; *Microbiota ; Risk Factors ; }, abstract = {Inflammatory bowel disease (IBD) is characterized by complex etiology and a disrupted colonic ecosystem. We provide a framework for the analysis of multi-omic data, which we apply to study the gut ecosystem in IBD. Specifically, we train and validate models using data on the metagenome, metatranscriptome, virome, and metabolome from the Human Microbiome Project 2 IBD multi-omic database, with 1,785 repeated samples from 130 individuals (103 cases and 27 controls). After splitting the participants into training and testing groups, we used mixed-effects least absolute shrinkage and selection operator regression to select features for each omic. These features, with demographic covariates, were used to generate separate single-omic prediction scores. All four single-omic scores were then combined into a final regression to assess the relative importance of the individual omics and the predictive benefits when considered together. We identified several species, pathways, and metabolites known to be associated with IBD risk, and we explored the connections between data sets. Individually, metabolomic and viromic scores were more predictive than metagenomics or metatranscriptomics, and when all four scores were combined, we predicted disease diagnosis with a Nagelkerke's R[2] of 0.46 and an area under the curve of 0.80 (95% confidence interval: 0.63, 0.98). Our work supports that some single-omic models for complex traits are more predictive than others, that incorporating multiple omic data sets may improve prediction, and that each omic data type provides a combination of unique and redundant information. This modeling framework can be extended to other complex traits and multi-omic data sets.IMPORTANCEComplex traits are characterized by many biological and environmental factors, such that multi-omic data sets are well-positioned to help us understand their underlying etiologies. We applied a prediction framework across multiple omics (metagenomics, metatranscriptomics, metabolomics, and viromics) from the gut ecosystem to predict inflammatory bowel disease (IBD) diagnosis. The predicted scores from our models highlighted key features and allowed us to compare the relative utility of each omic data set in single-omic versus multi-omic models. Our results emphasized the importance of metabolomics and viromics over metagenomics and metatranscriptomics for predicting IBD status. The greater predictive capability of metabolomics and viromics is likely because these omics serve as markers of lifestyle factors such as diet. This study provides a modeling framework for multi-omic data, and our results show the utility of combining multiple omic data types to disentangle complex disease etiologies and biological signatures.}, }
@article {pmid38094582, year = {2023}, author = {Luo, Y and Zhou, Y and Huang, P and Zhang, Q and Luan, F and Peng, Y and Wei, J and Li, N and Wang, C and Wang, X and Zhang, J and Yu, K and Zhao, M and Wang, C}, title = {Causal relationship between gut Prevotellaceae and risk of sepsis: a two-sample Mendelian randomization and clinical retrospective study in the framework of predictive, preventive, and personalized medicine.}, journal = {The EPMA journal}, volume = {14}, number = {4}, pages = {697-711}, pmid = {38094582}, issn = {1878-5077}, abstract = {OBJECTIVE: Gut microbiota is closely related to sepsis. Recent studies have suggested that Prevotellaceae could be associated with intestinal inflammation; however, the causal relationship between Prevotellaceae and sepsis remains uncertain. From the perspective of predictive, preventive, and personalized medicine (PPPM), exploring the causal relationship between gut Prevotellaceae and sepsis could provide opportunity for targeted prevention and personalized treatment.<br><br>METHODS: The genome-wide association study (GWAS) summary-level data of Prevotellaceae (N&#x2009;=&#x2009;7738) and sepsis were obtained from the Dutch Microbiome Project and the UK Biobank (sepsis, 1380 cases; 429,985 controls). MR analysis was conducted to estimate the associations between Prevotellaceae and sepsis risk. The 16S rRNA sequencing analysis was conducted to calculate the relative abundance of Prevotellaceae in sepsis patients to explore the relationship between Prevotellaceae relative abundance and the 28-day mortality.<br><br>RESULTS: Genetic liability to f__Prevotellaceae (OR, 1.91; CI, 1.35-2.71; p&#x2009;=&#x2009;0.0003) was associated with a high risk of sepsis with inverse-variance weighted (IVW). The median Prevotellaceae relative abundance in non-survivors was significantly higher than in survivors (2.34% vs 0.17%, p&#x2009;<&#x2009;0.001). Multivariate analysis confirmed that Prevotellaceae relative abundance (OR, 1.10; CI, 1.03-1.22; p&#x2009;=&#x2009;0.027) was an independent factor of 28-day mortality in sepsis patients. ROC curve analysis indicated that Prevotellaceae relative abundance (AUC: 0.787, 95% CI: 0.671-0.902, p&#x2009;=&#x2009;0.0003) could predict the prognosis of sepsis patients.<br><br>CONCLUSION: Our results revealed that Prevotellaceae was causally associated with sepsis and affected the prognosis of sepsis patients. These findings may provide insights to clinicians on developing improved sepsis PPPM strategies.<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13167-023-00340-6.}, }
@article {pmid38076824, year = {2023}, author = {Schweickart, A and Batra, R and Neth, BJ and Martino, C and Shenhav, L and Zhang, AR and Shi, P and Karu, N and Huynh, K and Meikle, PJ and Schimmel, L and Dilmore, AH and Blennow, K and Zetterberg, H and Blach, C and Dorrestein, PC and Knight, R and ,  and Craft, S and Kaddurah-Daouk, R and Krumsiek, J}, title = {A Modified Mediterranean Ketogenic Diet mitigates modifiable risk factors of Alzheimer's Disease: a serum and CSF-based metabolic analysis.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, pmid = {38076824}, support = {R01 AG046171/AG/NIA NIH HHS/United States ; U24 AG021886/AG/NIA NIH HHS/United States ; R01 AG069901/AG/NIA NIH HHS/United States ; U19 AG063744/AG/NIA NIH HHS/United States ; P30 AG049638/AG/NIA NIH HHS/United States ; UL1 TR001420/TR/NCATS NIH HHS/United States ; RF1 AG059093/AG/NIA NIH HHS/United States ; U01 AG061359/AG/NIA NIH HHS/United States ; RF1 AG057452/AG/NIA NIH HHS/United States ; P30 AG072947/AG/NIA NIH HHS/United States ; RF1 AG058942/AG/NIA NIH HHS/United States ; RF1 AG051550/AG/NIA NIH HHS/United States ; }, abstract = {Alzheimer's disease (AD) is influenced by a variety of modifiable risk factors, including a person's dietary habits. While the ketogenic diet (KD) holds promise in reducing metabolic risks and potentially affecting AD progression, only a few studies have explored KD's metabolic impact, especially on blood and cerebrospinal fluid (CSF). Our study involved participants at risk for AD, either cognitively normal or with mild cognitive impairment. The participants consumed both a modified Mediterranean-ketogenic diet (MMKD) and the American Heart Association diet (AHAD) for 6 weeks each, separated by a 6-week washout period. We employed nuclear magnetic resonance (NMR)-based metabolomics to profile serum and CSF and metagenomics profiling on fecal samples. While the AHAD induced no notable metabolic changes, MMKD led to significant alterations in both serum and CSF. These changes included improved modifiable risk factors, like increased HDL-C and reduced BMI, reversed serum metabolic disturbances linked to AD such as a microbiome-mediated increase in valine levels, and a reduction in systemic inflammation. Additionally, the MMKD was linked to increased amino acid levels in the CSF, a breakdown of branched-chain amino acids (BCAAs), and decreased valine levels. Importantly, we observed a strong correlation between metabolic changes in the CSF and serum, suggesting a systemic regulation of metabolism. Our findings highlight that MMKD can improve AD-related risk factors, reverse some metabolic disturbances associated with AD, and align metabolic changes across the blood-CSF barrier.}, }
@article {pmid38051644, year = {2023}, author = {Hou, T and Wang, Q and Dai, H and Hou, Y and Zheng, J and Wang, T and Lin, H and Wang, S and Li, M and Zhao, Z and Chen, Y and Xu, Y and Lu, J and Liu, R and Ning, G and Wang, W and Xu, M and Bi, Y}, title = {Interactive Association Between Gut Microbiota and Thyroid Cancer.}, journal = {Endocrinology}, volume = {165}, number = {1}, pages = {}, doi = {10.1210/endocr/bqad184}, pmid = {38051644}, issn = {1945-7170}, support = {81930021//National Natural Science Foundation of China/ ; SHDC2020CR1001A//Clinical Research Plan of SHDC/ ; 20152508//Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; Genome-Wide Association Study ; *Microbiota ; *Thyroid Neoplasms/genetics ; }, abstract = {CONTEXT: The association between the gut microbiota and thyroid cancer remains controversial.<br><br>OBJECTIVE: We aimed to systematically investigate the interactive causal relationships between the abundance and metabolism pathways of gut microbiota and thyroid cancer.<br><br>METHODS: We leveraged genome-wide association studies for the abundance of 211 microbiota taxa from the MiBioGen study (N = 18 340), 205 microbiota metabolism pathways from the Dutch Microbiome Project (N = 7738), and thyroid cancer from the Global Biobank Meta-analysis Initiative (N cases = 6699 and N participants = 1 620 354). We performed a bidirectional Mendelian randomization (MR) to investigate the causality from microbiota taxa and metabolism pathways to thyroid cancer and vice versa. We performed a systematic review of previous observational studies and compared MR results with observational findings.<br><br>RESULTS: Eight taxa and 12 metabolism pathways had causal effects on thyroid cancer, where RuminococcaceaeUCG004 genus (P = .001), Streptococcaceae family (P = .016), Olsenella genus (P = .029), ketogluconate metabolism pathway (P = .003), pentose phosphate pathway (P = .016), and L-arginine degradation II in the AST pathway (P = .0007) were supported by sensitivity analyses. Conversely, thyroid cancer had causal effects on 3 taxa and 2 metabolism pathways, where the Holdemanella genus (P = .015) was supported by sensitivity analyses. The Proteobacteria phylum, Streptococcaceae family, Ruminococcus2 genus, and Holdemanella genus were significantly associated with thyroid cancer in both the systematic review and MR, whereas the other 121 significant taxa in observational results were not supported by MR.<br><br>DISCUSSIONS: These findings implicated the potential role of host-microbiota crosstalk in thyroid cancer, while the discrepancy among observational studies calls for further investigations.}, }
@article {pmid38048079, year = {2023}, author = {Fu, P and Wu, Y and Zhang, Z and Qiu, Y and Wang, Y and Peng, Y}, title = {VIGA: a one-stop tool for eukaryotic virus identification and genome assembly from next-generation-sequencing data.}, journal = {Briefings in bioinformatics}, volume = {25}, number = {1}, pages = {}, pmid = {38048079}, issn = {1477-4054}, support = {32370700//National Natural Science Foundation of China/ ; 2022YFC2303802//National Key Plan for Scientific Research and Development of China/ ; }, mesh = {Humans ; High-Throughput Nucleotide Sequencing ; *Colitis, Ulcerative ; *Crohn Disease ; Genome, Viral ; Metagenome ; }, abstract = {Identification of viruses and further assembly of viral genomes from the next-generation-sequencing data are essential steps in virome studies. This study presented a one-stop tool named VIGA (available at https://github.com/viralInformatics/VIGA) for eukaryotic virus identification and genome assembly from NGS data. It was composed of four modules, namely, identification, taxonomic annotation, assembly and novel virus discovery, which integrated several third-party tools such as BLAST, Trinity, MetaCompass and RagTag. Evaluation on multiple simulated and real virome datasets showed that VIGA assembled more complete virus genomes than its competitors on both the metatranscriptomic and metagenomic data and performed well in assembling virus genomes at the strain level. Finally, VIGA was used to investigate the virome in metatranscriptomic data from the Human Microbiome Project and revealed different composition and positive rate of viromes in diseases of prediabetes, Crohn's disease and ulcerative colitis. Overall, VIGA would help much in identification and characterization of viromes, especially the known viruses, in future studies.}, }
@article {pmid38047279, year = {2023}, author = {Candeliere, F and Musmeci, E and Amaretti, A and Sola, L and Raimondi, S and Rossi, M}, title = {Profiling of the intestinal community of Clostridia: taxonomy and evolutionary analysis.}, journal = {Microbiome research reports}, volume = {2}, number = {2}, pages = {13}, pmid = {38047279}, issn = {2771-5965}, abstract = {Aim: Clostridia are relevant commensals of the human gut due to their major presence and correlations to the host. In this study, we investigated intestinal Clostridia of 51 healthy subjects and reconstructed their taxonomy and phylogeny. The relatively small number of intestinal Clostridia allowed a systematic whole genome approach based on average amino acid identity (AAI) and core genome with the aim of revising the current classification into genera and determining evolutionary relationships. Methods: 51 healthy subjects' metagenomes were retrieved from public databases. After the dataset's validation through comparison with Human Microbiome Project (HMP) samples, the metagenomes were profiled using MetaPhlAn3 to identify the population ascribed to the class Clostridia. Intestinal Clostridia genomes were retrieved and subjected to AAI analysis and core genome identification. Phylogeny investigation was conducted with RAxML and Unweighted Pair Group Method with Arithmetic Mean (UPGMA) algorithms, and SplitsTree for split decomposition. Results: 225 out of 406 bacterial taxonomic units were ascribed to Bacillota [Firmicutes], among which 124 were assigned to the class Clostridia. 77 out of the 124 taxonomic units were referred to a species, altogether covering 87.7% of Clostridia abundance. According to the lowest AAI genus boundary set at 55%, 15 putative genera encompassing more than one species (G1 to G15) were identified, while 19 species did not cluster with any other one and each appeared to belong to a diverse genus. Phylogenetic investigations highlighted that most of the species clustered into three main evolutive clades. Conclusion: This study shed light on the species of Clostridia colonizing the gut of healthy adults and pinpointed several gaps in knowledge regarding the taxonomy and the phylogeny of Clostridia.}, }
@article {pmid38045612, year = {2023}, author = {Brüssow, H}, title = {The human microbiome project at ten years - some critical comments and reflections on "our third genome", the human virome.}, journal = {Microbiome research reports}, volume = {2}, number = {1}, pages = {7}, pmid = {38045612}, issn = {2771-5965}, abstract = {The Human Microbiome Project (HMP) has raised great expectations claiming the far-reaching influence of the microbiome on human health and disease ranging from obesity and malnutrition to effects going well beyond the gut. So far, with the notable exception of fecal microbiota transplantation in Clostridioides difficile infection, practical application of microbiome intervention has only achieved modest clinical effects. It is argued here that we need criteria for the link between microbiome and disease modelled on the links between pathogens and infectious disease in Koch's postulates. The most important question is whether the microbiome change is a cause of the given disease or a consequence of a pathology leading to disease where the microbiome change is only a parallel event without a causal connection to the disease - in philosophical parlance, an epiphenomenon. Also discussed here is whether human virome research is a necessary complement to the microbiome project with a high potential for practical applications.}, }
@article {pmid38029073, year = {2023}, author = {Xie, Q and Hu, B}, title = {Effects of gut microbiota on prostatic cancer: a two-sample Mendelian randomization study.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1250369}, pmid = {38029073}, issn = {1664-302X}, abstract = {AIM: Recent observational and small-sample case-control studies have shown a relationship between gut microbiota composition and prostatic cancer (PCa). Nevertheless, the causal association between gut microbiota and PCa is still unclear. Herein, we used the Mendelian randomization (MR) method to explore the potential causal relationship between gut microbiota and PCa.<br><br>METHODS: In this two-sample MR study, data were extracted from the summary statistics of gut microbiota from the largest available genome-wide association study meta-analysis conducted by the MiBioGen consortium (n = 14,306) and the Dutch Microbiome Project (n = 8,208). Summary statistics for PCa were obtained from the FinnGen consortium release data (n = 95,213). Inverse variance weighted (IVW), MR-Egger, strength test (F), and MR-PRESSO were used to examine the potential causal association between gut microbiota and PCa. Cochran's Q statistics were used to quantify the heterogeneity of instrumental variables.<br><br>RESULTS: IVW estimates suggested that the relative abundance of Akkermansia muciniphila (odds ratio [OR] = 0.7926, 95% confidence interval [CI]: 0.6655-0.9440) and Bacteroides salyersiae (OR = 0.9023, 95% CI: 0.8262-0.9853) were negatively associated with the odds of PCa, while that of Eubacterium biforme (OR = 1.1629, 95% CI: 1.0110-1.3376) was positively associated with the odds of PCa. In addition, we explored these relationships among patients without other cancers and similarly found that the relative abundance of Akkermansia muciniphila, Bacteroides salyersiae, and Eubacterium biforme were linked to PCa (all P < 0.05).<br><br>CONCLUSION: Gut microbiota potentially influenced the occurrence of PCa. Our findings may provide some new ideas for researching the methods of PCa prevention. In addition, further studies are needed to explore the causal association and specific underlying mechanisms between gut microbiota and PCa.}, }
@article {pmid37973865, year = {2023}, author = {King, AM and Zhang, Z and Glassey, E and Siuti, P and Clardy, J and Voigt, CA}, title = {Systematic mining of the human microbiome identifies antimicrobial peptides with diverse activity spectra.}, journal = {Nature microbiology}, volume = {8}, number = {12}, pages = {2420-2434}, pmid = {37973865}, issn = {2058-5276}, support = {HR0011-15-C-0084//United States Department of Defense | Defense Advanced Research Projects Agency (DARPA)/ ; }, mesh = {Humans ; Antimicrobial Peptides ; *Methicillin-Resistant Staphylococcus aureus ; Escherichia coli ; Peptides/genetics/pharmacology/chemistry ; Bacteria/genetics ; *Microbiota/genetics ; Anti-Bacterial Agents/pharmacology ; }, abstract = {Human-associated bacteria secrete modified peptides to control host physiology and remodel the microbiota species composition. Here we scanned 2,229 Human Microbiome Project genomes of species colonizing skin, gastrointestinal tract, urogenital tract, mouth and trachea for gene clusters encoding RiPPs (ribosomally synthesized and post-translationally modified peptides). We found 218 lanthipeptides and 25 lasso peptides, 70 of which were synthesized and expressed in E. coli and 23 could be purified and functionally characterized. They were tested for activity against bacteria associated with healthy human flora and pathogens. New antibiotics were identified against strains implicated in skin, nasal and vaginal dysbiosis as well as from oral strains selectively targeting those in the gut. Extended- and narrow-spectrum antibiotics were found against methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococci. Mining natural products produced by human-associated microbes will enable the elucidation of ecological relationships and may be a rich resource for antimicrobial discovery.}, }
@article {pmid37940997, year = {2023}, author = {Dai, H and Hou, T and Wang, Q and Hou, Y and Zhu, Z and Zhu, Y and Zhao, Z and Li, M and Lin, H and Wang, S and Zheng, R and Xu, Y and Lu, J and Wang, T and Ning, G and Wang, W and Zheng, J and Bi, Y and Xu, M}, title = {Roles of gut microbiota in atrial fibrillation: insights from Mendelian randomization analysis and genetic data from over 430,000 cohort study participants.}, journal = {Cardiovascular diabetology}, volume = {22}, number = {1}, pages = {306}, pmid = {37940997}, issn = {1475-2840}, mesh = {*Atrial Fibrillation/diagnosis/epidemiology/genetics ; Cohort Studies ; *Diabetes Mellitus, Type 2 ; *Gastrointestinal Microbiome ; Eubacterium ; Humans ; Genome-Wide Association Study ; Mendelian Randomization Analysis ; *Coronary Artery Disease ; }, abstract = {BACKGROUND: Gut microbiota imbalances have been suggested as a contributing factor to atrial fibrillation (AF), but the causal relationship is not fully understood.<br><br>OBJECTIVES: To explore the causal relationships between the gut microbiota and AF using Mendelian randomization (MR) analysis.<br><br>METHODS: Summary statistics were from genome-wide association studies (GWAS) of 207 gut microbial taxa (5 phyla, 10 classes, 13 orders, 26 families, 48 genera, and 105 species) (the Dutch Microbiome Project) and two large meta-GWASs of AF. The significant results were validated in FinnGen cohort and over 430,000 UK Biobank participants. Mediation MR analyses were conducted for AF risk factors, including type 2 diabetes, coronary artery disease (CAD), body mass index (BMI), blood lipids, blood pressure, and obstructive sleep apnea, to explore the potential mediation effect of these risk factors in between the gut microbiota and AF.<br><br>RESULTS: Two microbial taxa causally associated with AF: species Eubacterium ramulus (odds ratio [OR] 1.08, 95% confidence interval [CI] 1.04-1.12, P&#x2009;=&#x2009;0.0001, false discovery rate (FDR) adjusted p-value&#x2009;=&#x2009;0.023) and genus Holdemania (OR 1.15, 95% CI 1.07-1.25, P&#x2009;=&#x2009;0.0004, FDR adjusted p-value&#x2009;=&#x2009;0.042). Genus Holdemania was associated with incident AF risk in the UK Biobank. The proportion of mediation effect of species Eubacterium ramulus via CAD was 8.05% (95% CI 1.73% -&#x2009;14.95%, P&#x2009;=&#x2009;0.008), while the proportion of genus Holdemania on AF via BMI was 12.01% (95% CI 5.17% -&#x2009;19.39%, P&#x2009;=&#x2009;0.0005).<br><br>CONCLUSIONS: This study provided genetic evidence to support a potential causal mechanism between gut microbiota and AF and suggested the mediation role of AF risk factors.}, }
@article {pmid37875417, year = {2024}, author = {Li, J and Yang, Z and Yuan, W and Bao, Z and Li, MD}, title = {Heme Metabolism Mediates the Effects of Smoking on Gut Microbiome.}, journal = {Nicotine &amp; tobacco research : official journal of the Society for Research on Nicotine and Tobacco}, volume = {26}, number = {6}, pages = {742-751}, doi = {10.1093/ntr/ntad209}, pmid = {37875417}, issn = {1469-994X}, support = {2016YFC0906300//China Precision Medicine Initiative/ ; 2021539200340045//Joint Research Institute of Tobacco and Health of China/ ; //Research Center for Air Pollution and Health of Zhejiang University/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; *Heme/metabolism ; Transcriptome ; Male ; Female ; Metagenome ; Adult ; Smoking/adverse effects ; Bacteroides/genetics ; }, abstract = {INTRODUCTION: The number of smokers worldwide increased greatly during the past decades and reached 1.14 billion in 2019, becoming a leading risk factor for human health. Tobacco smoking has wide effects on human genetics, epigenetics, transcriptome, and gut microbiome. Although many studies have revealed effects of smoking on host transcriptome, research on the relationship between smoking, host gene expression, and the gut microbiome is limited.<br><br>AIMS AND METHODS: We first explored transcriptome and metagenome profile differences between smokers and nonsmokers. To evaluate the relationship between host gene expression and gut microbiome, we then applied bidirectional mediation analysis to infer causal relationships between smoking, gene expression, and gut microbes.<br><br>RESULTS: Metagenome and transcriptome analyses revealed 71 differential species and 324 differential expressed genes between smokers and nonsmokers. With smoking as an exposure variable, we identified 272 significant causal relationships between gene expression and gut microbes, among which there were 247 genes that mediate the effect of smoking on gut microbes. Pathway-based enrichment analysis showed that these genes were significantly enriched in heme metabolic pathway, which mainly mediated the changes of Bacteroides finegoldii and Lachnospiraceae bacterium 9_1_43BFAA. Additionally, by performing metabolome data analysis in the Integrated Human Microbiome Project (iHMP) database, we verified the correlation between the intermediate products of the heme metabolism pathway (porphobilinogen, bilirubin, and biliverdin) and gut microbiome.<br><br>CONCLUSIONS: By investigating the bidirectional interaction between smoking-related host gene expression and gut microbes, this study provided evidence for the mediation of smoking on gut microbes through co-involvement or interaction of heme metabolism.<br><br>IMPLICATIONS: By comparing the metagenome and transcriptome sequencing profiles between 34 smokers and 33 age- and gender-matched nonsmokers, we are the first to reveal causal relationships among tobacco smoking, host gene expression, and gut microbes. These findings offer insight into how smoking affects gut microbes through host gene expression and metabolism, which highlights the importance of heme metabolism in modulating the effects of smoking on gut microbiome.}, }
@article {pmid37874170, year = {2023}, author = {Brostow, DP and Donovan, M and Penzenik, M and Stamper, CE and Spark, T and Lowry, CA and Ishaq, SL and Hoisington, AJ and Brenner, LA}, title = {Food desert residence has limited impact on veteran fecal microbiome composition: a U.S. Veteran Microbiome Project study.}, journal = {mSystems}, volume = {8}, number = {6}, pages = {e0071723}, pmid = {37874170}, issn = {2379-5077}, support = {//U.S. Department of Veterans Affairs (VA)/ ; }, mesh = {Humans ; Food Deserts ; *Veterans/psychology ; *Microbiota ; Feces ; *Gastrointestinal Microbiome ; }, abstract = {Social and economic inequities can have a profound impact on human health. The inequities could result in alterations to the gut microbiome, an important factor that may have profound abilities to alter health outcomes. Moreover, the strong correlations between social and economic inequities have been long understood. However, to date, limited research regarding the microbiome and mental health within the context of socioeconomic inequities exists. One particular inequity that may influence both mental health and the gut microbiome is living in a food desert. Persons living in food deserts may lack access to sufficient and/or nutritious food and often experience other inequities, such as increased exposure to air pollution and poor access to healthcare. Together, these factors may confer a unique risk for microbial perturbation. Indeed, external factors beyond a food desert might compound over time to have a lasting effect on an individual's gut microbiome. Therefore, adoption of a life-course approach is expected to increase the ecological validity of research related to social inequities, the gut microbiome, and physical and mental health.}, }
@article {pmid37810788, year = {2023}, author = {Ochoa-Sánchez, M and Acuña Gomez, EP and Ramírez-Fenández, L and Eguiarte, LE and Souza, V}, title = {Current knowledge of the Southern Hemisphere marine microbiome in eukaryotic hosts and the Strait of Magellan surface microbiome project.}, journal = {PeerJ}, volume = {11}, number = {}, pages = {e15978}, pmid = {37810788}, issn = {2167-8359}, mesh = {Animals ; *Eukaryota/genetics ; RNA, Ribosomal, 16S/genetics ; *Microbiota/genetics ; Metagenome ; Fishes/genetics ; Aquatic Organisms/genetics ; Mammals/genetics ; }, abstract = {Host-microbe interactions are ubiquitous and play important roles in host biology, ecology, and evolution. Yet, host-microbe research has focused on inland species, whereas marine hosts and their associated microbes remain largely unexplored, especially in developing countries in the Southern Hemisphere. Here, we review the current knowledge of marine host microbiomes in the Southern Hemisphere. Our results revealed important biases in marine host species sampling for studies conducted in the Southern Hemisphere, where sponges and marine mammals have received the greatest attention. Sponge-associated microbes vary greatly across geographic regions and species. Nevertheless, besides taxonomic heterogeneity, sponge microbiomes have functional consistency, whereas geography and aging are important drivers of marine mammal microbiomes. Seabird and macroalgal microbiomes in the Southern Hemisphere were also common. Most seabird microbiome has focused on feces, whereas macroalgal microbiome has focused on the epibiotic community. Important drivers of seabird fecal microbiome are aging, sex, and species-specific factors. In contrast, host-derived deterministic factors drive the macroalgal epibiotic microbiome, in a process known as "microbial gardening". In turn, marine invertebrates (especially crustaceans) and fish microbiomes have received less attention in the Southern Hemisphere. In general, the predominant approach to study host marine microbiomes has been the sequencing of the 16S rRNA gene. Interestingly, there are some marine holobiont studies (i.e., studies that simultaneously analyze host (e.g., genomics, transcriptomics) and microbiome (e.g., 16S rRNA gene, metagenome) traits), but only in some marine invertebrates and macroalgae from Africa and Australia. Finally, we introduce an ongoing project on the surface microbiome of key species in the Strait of Magellan. This is an international project that will provide novel microbiome information of several species in the Strait of Magellan. In the short-term, the project will improve our knowledge about microbial diversity in the region, while long-term potential benefits include the use of these data to assess host-microbial responses to the Anthropocene derived climate change.}, }
@article {pmid37790319, year = {2023}, author = {Jansen, R and Milaneschi, Y and Schranner, D and Kastenmuller, G and Arnold, M and Han, X and Dunlop, BW and ,  and Rush, AJ and Kaddurah-Daouk, R and Penninx, BW}, title = {The Metabolome-Wide Signature of Major Depressive Disorder.}, journal = {Research square}, volume = {}, number = {}, pages = {}, pmid = {37790319}, issn = {2693-5015}, support = {R01 AG046171/AG/NIA NIH HHS/United States ; R01 MH108348/MH/NIMH NIH HHS/United States ; R01 AG069901/AG/NIA NIH HHS/United States ; U19 AG063744/AG/NIA NIH HHS/United States ; RF1 AG059093/AG/NIA NIH HHS/United States ; U01 AG061359/AG/NIA NIH HHS/United States ; RF1 AG057452/AG/NIA NIH HHS/United States ; RF1 AG058942/AG/NIA NIH HHS/United States ; RF1 AG051550/AG/NIA NIH HHS/United States ; }, abstract = {Major Depressive Disorder (MDD) is an often-chronic condition with substantial molecular alterations and pathway dysregulations involved. Single metabolite, pathway and targeted metabolomics platforms have indeed revealed several metabolic alterations in depression including energy metabolism, neurotransmission and lipid metabolism. More comprehensive coverage of the metabolome is needed to further specify metabolic dysregulation in depression and reveal previously untargeted mechanisms. Here we measured 820 metabolites using the metabolome-wide Metabolon platform in 2770 subjects from a large Dutch clinical cohort with extensive depression clinical phenotyping (1101 current MDD, 868 remitted MDD, 801 healthy controls) at baseline and 1805 subjects at 6-year follow up (327 current MDD, 1045 remitted MDD, 433 healthy controls). MDD diagnosis was based on DSM-IV psychiatric interviews. Depression severity was measured with the Inventory of Depressive Symptomatology self-report. Associations between metabolites and MDD status and depression severity were assessed at baseline and at the 6-year follow-up. Metabolites consistently associated with MDD status or depression severity on both occasions were examined in Mendelian randomization (MR) analysis using metabolite (N=14,000) and MDD (N=800,000) GWAS results. At baseline, 139 and 126 metabolites were associated with current MDD status and depression severity, respectively, with 79 overlapping metabolites. Six years later, 34 out of the 79 metabolite associations were subsequently replicated. Downregulated metabolites were enriched with long-chain monounsaturated (P=6.7e-07) and saturated (P=3.2e-05) fatty acids and upregulated metabolites with lysophospholipids (P=3.4e-4). Adding BMI to the models changed results only marginally. MR analyses showed that genetically-predicted higher levels of the lysophospholipid 1-linoleoyl-GPE (18:2) were associated with greater risk of depression. The identified metabolome-wide profile of depression (severity) indicated altered lipid metabolism with downregulation of long-chain fatty acids and upregulation of lysophospholipids, for which causal involvement was suggested using genetic tools. This metabolomics signature offers a window on depression pathophysiology and a potential access point for the development of novel therapeutic approaches.}, }
@article {pmid37747198, year = {2023}, author = {Duan, Z and Fu, J and Zhang, F and Cai, Y and Wu, G and Ma, W and Zhou, H and He, Y}, title = {The association between BMI and serum uric acid is partially mediated by gut microbiota.}, journal = {Microbiology spectrum}, volume = {11}, number = {5}, pages = {e0114023}, pmid = {37747198}, issn = {2165-0497}, abstract = {Obesity is a risk factor for the development of hyperuricemia, both of which were related to gut microbiota. However, whether alterations in the gut microbiota lie in the pathways mediating obesity's effects on hyperuricemia is less clear. Body mass index (BMI) and serum uric acid (SUA) were separately important indicators of obesity and hyperuricemia. Our study aims to investigate whether BMI-related gut microbiota characteristics would mediate the association between BMI and SUA levels. A total of 6,280 participants from Guangdong Gut Microbiome Project were included in this study. Stool samples were collected for 16S rRNA gene sequencing. The results revealed that BMI was significantly and positively associated with SUA. Meanwhile, BMI was significantly associated with the abundance of 102 gut microbial genera, 16 of which were also significantly associated with SUA. The mediation analysis revealed that the association between BMI and SUA was partially mediated by the abundance of Proteobacteria (proportion mediated: 0.94%, P < 0.05). At the genus level, 25 bacterial genera, including Ralstonia, Oscillospira, Faecalibacterium, etc., could also partially mediate the association of BMI with SUA (the highest proportion is mediated by Ralstonia, proportion mediated: 2.76%, P < 0.05). This study provided evidence for the associations among BMI, gut microbiota, and SUA, and the mediation analysis suggested that the association of BMI with SUA was partially mediated by the gut microbiota. IMPORTANCE Using 16S rRNA sequencing analysis, local interpretable machine learning technique analysis and mediation analysis were used to explore the association between BMI with SUA, and the mediating effects of gut microbial dysbiosis in the association were investigated.}, }
@article {pmid37719161, year = {2023}, author = {Hayer, SS and Hwang, S and Clayton, JB}, title = {Antibiotic-induced gut dysbiosis and cognitive, emotional, and behavioral changes in rodents: a systematic review and meta-analysis.}, journal = {Frontiers in neuroscience}, volume = {17}, number = {}, pages = {1237177}, pmid = {37719161}, issn = {1662-4548}, support = {K01 OD030514/OD/NIH HHS/United States ; }, abstract = {There are previous epidemiological studies reporting associations between antibiotic use and psychiatric symptoms. Antibiotic-induced gut dysbiosis and alteration of microbiota-gut-brain axis communication has been proposed to play a role in this association. In this systematic review and meta-analysis, we reviewed published articles that have presented results on changes in cognition, emotion, and behavior in rodents (rats and mice) after antibiotic-induced gut dysbiosis. We searched three databases-PubMed, Web of Science, and SCOPUS to identify such articles using dedicated search strings and extracted data from 48 articles. Increase in anxiety and depression-like behavior was reported in 32.7 and 40.7 percent of the study-populations, respectively. Decrease in sociability, social novelty preference, recognition memory and spatial cognition was found in 18.1, 35.3, 26.1, and 62.5 percent of the study-populations, respectively. Only one bacterial taxon (increase in gut Proteobacteria) showed statistically significant association with behavioral changes (increase in anxiety). There were no consistent findings with statistical significance for the potential biomarkers [Brain-derived neurotrophic factor (BDNF) expression in the hippocampus, serum corticosterone and circulating IL-6 and IL-1β levels]. Results of the meta-analysis revealed a significant association between symptoms of negative valence system (including anxiety and depression) and cognitive system (decreased spatial cognition) with antibiotic intake (p < 0.05). However, between-study heterogeneity and publication bias were statistically significant (p < 0.05). Risk of bias was evaluated to be high in the majority of the studies. We identified and discussed several reasons that could contribute to the heterogeneity between the results of the studies examined. The results of the meta-analysis provide promising evidence that there is indeed an association between antibiotic-induced gut dysbiosis and psychopathologies. However, inconsistencies in the implemented methodologies make generalizing these results difficult. Gut microbiota depletion using antibiotics may be a useful strategy to evaluate if and how gut microbes influence cognition, emotion, and behavior, but the heterogeneity in methodologies used precludes any definitive interpretations for a translational impact on clinical practice.}, }
@article {pmid37655719, year = {2023}, author = {Corewyn, LC and Kelaita, MA and Nollman, J and Hagnauer, I and Blanco-Peña, K and Lessnau, RG and Clayton, JB and Shields-Cutler, R and Stoos, KB}, title = {Hematology and blood biochemistry in a declining population of mantled howler monkeys (Alouatta palliata palliata) at La Pacifica, Costa Rica.}, journal = {Journal of medical primatology}, volume = {52}, number = {6}, pages = {353-360}, pmid = {37655719}, issn = {1600-0684}, support = {K01 OD030514/OD/NIH HHS/United States ; }, mesh = {Female ; Male ; Animals ; Costa Rica ; *Alouatta ; *Alouatta caraya ; *Hematology ; }, abstract = {BACKGROUND: Alouatta palliata palliata are an ecologically flexible howler monkey subspecies that has recently been relisted as Endangered. Populations are declining through much of the subspecies' range, including at our study site at La Pacifica, Costa Rica. Our objectives were to screen blood hematology and biochemistry samples collected from this wild population to elucidate their baseline health.<br><br>METHODS: We collected blood samples from 38 adult individuals from across the study site and analyzed 13 hematology and 14 biochemistry parameters.<br><br>RESULTS: Most hematology and blood biochemistry parameter values were similar between males and females. However, mean hemoglobin was significantly lower, and mean white blood cell count was significantly higher in females; and mean calcium and mean creatinine were significantly lower in females compared to males.<br><br>CONCLUSIONS: Overall, the La Pacifica population appeared healthy based on the blood parameters analyzed from sampled individuals. Our results were also largely consistent with published data available from other populations of A.&#x2009;p.&#x2009;palliata, and with reference values for captive Alouatta caraya.}, }
@article {pmid37644161, year = {2023}, author = {Koo, H and Morrow, CD}, title = {Identification of donor Bacteroides vulgatus genes encoding proteins that correlate with early colonization following fecal transplant of patients with recurrent Clostridium difficile.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {14112}, pmid = {37644161}, issn = {2045-2322}, mesh = {Child ; Humans ; Animals ; Mice ; *Fecal Microbiota Transplantation ; *Clostridioides difficile/genetics ; Tissue Donors ; Bacteroides/genetics ; }, abstract = {Due to suppressive antibiotics, patients with recurrent Clostridium difficile have gut microbial communities that are devoid of most commensal microbes. Studies have shown that most of the failures using fecal microbe transplantation (FMT) for recurrent C. difficile occur during the first 4 weeks following transplantation. To identify features of donor Bacteroides vulgatus that lead to early colonization, we used two data sets that collected fecal samples from recipients at early times points post FMT. The first analysis used the shotgun metagenomic DNA sequencing data set from Aggarwala et al. consisting of 7 FMT donors and 13 patients with recurrent C. difficile with fecal samples taken as early as 24 h post FMT. We identified 2 FMT donors in which colonization of recipients by donor B. vulgatus was detected as early as 24 h post FMT. We examined a second data set from Hourigan et al. that collected fecal samples from C. difficile infected children and identified 1 of 3 FMT that also had early colonization of the donor B. vulgatus. We found 19 genes out of 4911 encoding proteins were unique to the 3 donors that had early colonization. A gene encoding a putative chitobiase was identified that was in a gene complex that had been previously identified to enhance colonization in mice. A gene encoding a unique fimbrillin (i.e., pili) family protein and 17 genes encoding hypothetical proteins were also specific for early colonizing donors. Most of the genes encoding hypothetical proteins had neighboring genes that encoded proteins involved in mobilization or transposition. Finally, analysis of 42 paired fecal samples from the human microbiome project (HMP) found no individuals had all 19 genes while 2 individuals had none of the 19 genes. Based on the results from our study, consideration should be given to the screening of FMT donors for these B. vulgatus genes found to enhance early colonization that would be of benefit to promote colonization following FMT.}, }
@article {pmid37642431, year = {2023}, author = {Farmer, N and Maki, KA and Barb, JJ and Jones, KK and Yang, L and Baumer, Y and Powell-Wiley, TM and Wallen, GR}, title = {Geographic social vulnerability is associated with the alpha diversity of the human microbiome.}, journal = {mSystems}, volume = {8}, number = {5}, pages = {e0130822}, pmid = {37642431}, issn = {2379-5077}, mesh = {Humans ; *Social Vulnerability ; *Microbiota/genetics ; Geography ; Risk Factors ; Public Health ; }, abstract = {As a risk factor for conditions related to the microbiome, understanding the role of SVI on microbiome diversity may assist in identifying public health implications for microbiome research. Here we found, using a sub-sample of the Human Microbiome Project phase 1 cohort, that SVI was linked to microbiome diversity across body sites and that SVI may influence race/ethnicity-based differences in diversity. Our findings, build on the current knowledge regarding the role of human geography in microbiome research, suggest that measures of geographic social vulnerability be considered as additional contextual factors when exploring microbiome alpha diversity.}, }
@article {pmid37637212, year = {2023}, author = {Li, W and Mirone, J and Prasad, A and Miolane, N and Legrand, C and Dao Duc, K}, title = {Orthogonal outlier detection and dimension estimation for improved MDS embedding of biological datasets.}, journal = {Frontiers in bioinformatics}, volume = {3}, number = {}, pages = {1211819}, pmid = {37637212}, issn = {2673-7647}, abstract = {Conventional dimensionality reduction methods like Multidimensional Scaling (MDS) are sensitive to the presence of orthogonal outliers, leading to significant defects in the embedding. We introduce a robust MDS method, called DeCOr-MDS (Detection and Correction of Orthogonal outliers using MDS), based on the geometry and statistics of simplices formed by data points, that allows to detect orthogonal outliers and subsequently reduce dimensionality. We validate our methods using synthetic datasets, and further show how it can be applied to a variety of large real biological datasets, including cancer image cell data, human microbiome project data and single cell RNA sequencing data, to address the task of data cleaning and visualization.}, }
@article {pmid37637104, year = {2023}, author = {Gois, MFB and Fernández-Pato, A and Huss, A and Gacesa, R and Wijmenga, C and Weersma, RK and Fu, J and Vermeulen, RCH and Zhernakova, A and Lenters, VC and Kurilshikov, A}, title = {Impact of occupational pesticide exposure on the human gut microbiome.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1223120}, pmid = {37637104}, issn = {1664-302X}, abstract = {The rising use of pesticides in modern agriculture has led to a shift in disease burden in which exposure to these chemicals plays an increasingly important role. The human gut microbiome, which is partially responsible for the biotransformation of xenobiotics, is also known to promote biotransformation of environmental pollutants. Understanding the effects of occupational pesticide exposure on the gut microbiome can thus provide valuable insights into the mechanisms underlying the impact of pesticide exposure on health. Here we investigate the impact of occupational pesticide exposure on human gut microbiome composition in 7198 participants from the Dutch Microbiome Project of the Lifelines Study. We used job-exposure matrices in combination with occupational codes to retrieve categorical and cumulative estimates of occupational exposures to general pesticides, herbicides, insecticides and fungicides. Approximately 4% of our cohort was occupationally exposed to at least one class of pesticides, with predominant exposure to multiple pesticide classes. Most participants reported long-term employment, suggesting a cumulative profile of exposure. We demonstrate that contact with insecticides, fungicides and a general "all pesticides" class was consistently associated with changes in the gut microbiome, showing significant associations with decreased alpha diversity and a differing beta diversity. We also report changes in the abundance of 39 different bacterial taxa upon exposure to the different pesticide classes included in this study. Together, the extent of statistically relevant associations between gut microbial changes and pesticide exposure in our findings highlights the impact of these compounds on the human gut microbiome.}, }
@article {pmid37630647, year = {2023}, author = {Zhang, F and Zhang, X and Fu, J and Duan, Z and Qiu, W and Cai, Y and Ma, W and Zhou, H and Chen, Y and Zheng, J and He, Y}, title = {Sex- and Age-Dependent Associations between Parabacteroides and Obesity: Evidence from Two Population Cohort.}, journal = {Microorganisms}, volume = {11}, number = {8}, pages = {}, pmid = {37630647}, issn = {2076-2607}, support = {82022044//National Natural Science Foundation of China/ ; }, abstract = {Parabacteroides levels are reported to be low in obese individuals, and this genus has shown an anti-obesity capacity in animal studies. Nevertheless, the relationship between Parabacteroides and obesity in different subpopulations, e.g., with respect to age and sex, and its association with subsequent weight change have rarely been explored. The cross-sectional associations of Parabacteroides genus- and species-level OTU abundance with obesity were explored in the Guangdong Gut Microbiome Project (GGMP), which included 5843 adults, and replicated in the Guangzhou Nutrition and Health Study (GNSH), which included 1637 individuals. Furthermore, we assessed the prospective associations of Parabacteroides and its main OTUs' abundance with the subsequent changes in body mass index (BMI) in the GNSH. We found that Parabacteroides was inversely associated with obesity among females and participants aged 40-69 years in the GGMP and the replicated cohort in the GNSH. After a 3-year follow-up, there was no significant correlation between Parabacteroides and the subsequent changes in BMI. However, Seq4172 (P. johnsonii) showed a negative correlation with subsequent BMI changes in the female and middle-aged (40-69 years) subpopulations. Overall, our results indicate that Parabacteroides have an inverse relationship with obesity and that Seq4172 (P. johnsonii) have a negative association with subsequent changes in BMI among females and middle-aged populations in perspective analyses.}, }
@article {pmid37626146, year = {2023}, author = {Singh, S and Singh, S and Lukas, SB and Machado, S and Nouri, A and Calderon, F and Rieke, ER and Cappellazzi, SB}, title = {Long-term agro-management strategies shape soil bacterial community structure in dryland wheat systems.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {13929}, pmid = {37626146}, issn = {2045-2322}, mesh = {*Soil ; Triticum ; Carbon Dioxide ; Agriculture ; *Calcinosis ; Carbon ; }, abstract = {Soil microbes play a crucial role in soil organic matter decomposition and nutrient cycling and are influenced by management practices. Therefore, quantifying the impacts of various agricultural management practices on soil microbiomes and their activity is crucial for making informed management decisions. This study aimed to assess the impact of various management systems on soil bacterial abundance and diversity, soil enzyme activities and carbon mineralization potential in wheat-based systems. To accomplish this, soil samples from 0 to 15 cm depth were collected from ongoing long-term field trials in eastern Oregon region under wheat (Triticum aestivum L.)-fallow (WF), WF with different tillage (WT), wheat-pea (Pisum sativum L.) (WP), WF under different crop residue management (CR) and natural undisturbed/unmanaged grassland pasture (GP). These trials consisted of an array of treatments like tillage intensities, nitrogen rates, organic amendments, and seasonal residue burning. This study was a part of the Soil Health Institute's North American Project to Evaluate Soil Health measurements (NAPESHM). Bacterial community structure was determined using amplicon sequencing of the V4 region of 16SrRNA genes and followed the protocols of the Earth Microbiome Project. In addition, extracellular enzyme activities, and carbon mineralization potential (1d-CO2) were measured. Among different trials, 1d-CO2 in WT, WP, and CR studies averaged 53%, 51% and 87% lower than GP systems, respectively. Enzyme activities were significantly greater in GP compared to the other managements and followed similar trend as respiration. We observed higher evenness in GP and higher richness in spring residue burning treatment of CR study. Our results indicated that species evenness is perhaps a better indicator of soil health in comparison to other indices in dryland wheat systems.}, }
@article {pmid37619924, year = {2023}, author = {Golovko, G and Khanipov, K and Reyes, V and Pinchuk, I and Fofanov, Y}, title = {Identification of multivariable Boolean patterns in microbiome and microbial gene composition data.}, journal = {Bio Systems}, volume = {233}, number = {}, pages = {105007}, doi = {10.1016/j.biosystems.2023.105007}, pmid = {37619924}, issn = {1872-8324}, abstract = {Virtually every biological system is governed by complex relations among its components. Identifying such relations requires a rigorous or heuristics-based search for patterns among variables/features of a system. Various algorithms have been developed to identify two-dimensional (involving two variables) patterns employing correlation, covariation, mutual information, etc. It seems obvious, however, that comprehensive descriptions of complex biological systems need also to include more complicated multivariable relations, which can only be described using patterns that simultaneously embrace 3, 4, and more variables. The goal of this manuscript is to (a) introduce a novel type of associations (multivariable Boolean patterns) that can be manifested between features of complex systems but cannot be identified (described) by traditional pair-vise metrics; (b) propose patterns classification method, and (c) provide a novel definition of the pattern's strength (pattern's score) able to accommodate heterogeneous multi-omics data. To demonstrate the presence of such patterns, we performed a search for all possible 2-, 3-, and 4-dimensional patterns in historical data from the Human Microbiome Project (15 body sites) and collection of H. pylori genomes associated with gastric ulcers, gastritis, and duodenal ulcers. In all datasets under consideration, we were able to identify hundreds of statistically significant multivariable patterns. These results suggest that such patterns can be common in microbial genomics/microbiomics systems.}, }
@article {pmid37569821, year = {2023}, author = {Dong, H and Ming, D}, title = {A Comprehensive Self-Resistance Gene Database for Natural-Product Discovery with an Application to Marine Bacterial Genome Mining.}, journal = {International journal of molecular sciences}, volume = {24}, number = {15}, pages = {}, pmid = {37569821}, issn = {1422-0067}, support = {2019YFA0905700, 2021YFC2102700//the National Key Research and Development Program of China/ ; }, abstract = {In the world of microorganisms, the biosynthesis of natural products in secondary metabolism and the self-resistance of the host always occur together and complement each other. Identifying resistance genes from biosynthetic gene clusters (BGCs) helps us understand the self-defense mechanism and predict the biological activity of natural products synthesized by microorganisms. However, a comprehensive database of resistance genes is still lacking, which hinders natural product annotation studies in large-scale genome mining. In this study, we compiled a resistance gene database (RGDB) by scanning the four available databases: CARD, MIBiG, NCBIAMR, and UniProt. Every resistance gene in the database was annotated with resistance mechanisms and possibly involved chemical compounds, using manual annotation and transformation from the resource databases. The RGDB was applied to analyze resistance genes in 7432 BGCs in 1390 genomes from a marine microbiome project. Our calculation showed that the RGDB successfully identified resistance genes for more than half of the BGCs, suggesting that the database helps prioritize BGCs that produce biologically active natural products.}, }
@article {pmid37533836, year = {2023}, author = {Su, Q and Jin, C and Bo, Z and Yang, Y and Wang, J and Wang, J and Zhou, J and Chen, Y and Zeng, H and Chen, G and Wang, Y}, title = {Association between gut microbiota and gastrointestinal cancer: a two-sample bi-directional Mendelian randomization study.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1181328}, pmid = {37533836}, issn = {1664-302X}, abstract = {BACKGROUND: The gut microbiome is closely related to gastrointestinal (GI) cancer, but the causality of gut microbiome with GI cancer has yet to be fully established. We conducted this two-sample Mendelian randomization (MR) study to reveal the potential causal effect of gut microbiota on GI cancer.<br><br>MATERIALS AND METHODS: Summary-level genetic data of gut microbiome were derived from the MiBioGen consortium and the Dutch Microbiome Project. Summary statistics of six GI cancers were drawn from United Kingdom Biobank. Inverse-variance-weighted (IVW), MR-robust adjusted profile score (MR-RAPS), and weighted-median (WM) methods were used to evaluate the potential causal link between gut microbiota and GI cancer. In addition, we performed sensitivity analyses and reverse MR analyses.<br><br>RESULTS: We identified potential causal associations between 21 bacterial taxa and GI cancers (values of p <&#x2009;0.05 in all three MR methods). Among them, phylum Verrucomicrobia (OR: 0.17, 95% CI: 0.05-0.59, p =&#x2009;0.005) retained a strong negative association with intrahepatic cholangiocarcinoma after the Bonferroni correction, whereas order Bacillales (OR: 1.67, 95% CI: 1.23-2.26, p =&#x2009;0.001) retained a strong positive association with pancreatic cancer. Reverse MR analyses indicated that GI cancer was associated with 17 microbial taxa in all three MR methods, among them, a strong inverse association between colorectal cancer and family Clostridiaceae1 (OR: 0.91, 95% CI: 0.86-0.96, p =&#x2009;0.001) was identified by Bonferroni correction.<br><br>CONCLUSION: Our study implicates the potential causal effects of specific microbial taxa on GI cancer, potentially providing new insights into the prevention and treatment of GI cancer through specific gut bacteria.}, }
@article {pmid37379424, year = {2023}, author = {Seabourn, PS and Weber, DE and Spafford, H and Medeiros, MCI}, title = {Aedes albopictus microbiome derives from environmental sources and partitions across distinct host tissues.}, journal = {MicrobiologyOpen}, volume = {12}, number = {3}, pages = {e1364}, pmid = {37379424}, issn = {2045-8827}, support = {P20 GM125508/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; *Aedes/microbiology ; *Microbiota ; Life Cycle Stages ; Soil ; Symbiosis ; }, abstract = {The mosquito microbiome consists of a consortium of interacting microorganisms that reside on and within culicid hosts. Mosquitoes acquire most of their microbial diversity from the environment over their life cycle. Once present within the mosquito host, the microbes colonize distinct tissues, and these symbiotic relationships are maintained by immune-related mechanisms, environmental filtering, and trait selection. The processes that govern how environmental microbes assemble across the tissues within mosquitoes remain poorly resolved. We use ecological network analyses to examine how environmental bacteria assemble to form bacteriomes among Aedes albopictus host tissues. Mosquitoes, water, soil, and plant nectar were collected from 20 sites in the Mānoa Valley, Oahu. DNA was extracted and associated bacteriomes were inventoried using Earth Microbiome Project protocols. We find that the bacteriomes of A. albopictus tissues were compositional taxonomic subsets of environmental bacteriomes and suggest that the environmental microbiome serves as a source pool that supports mosquito microbiome diversity. Within the mosquito, the microbiomes of the crop, midgut, Malpighian tubules, and ovaries differed in composition. This microbial diversity partitioned among host tissues formed two specialized modules: one in the crop and midgut, and another in the Malpighian tubules and ovaries. The specialized modules may form based on microbe niche preferences and/or selection of mosquito tissues for specific microbes that aid unique biological functions of the tissue types. A strong niche-driven assembly of tissue-specific microbiotas from the environmental species pool suggests that each tissue has specialized associations with microbes, which derive from host-mediated microbe selection.}, }
@article {pmid37331612, year = {2023}, author = {Adelfio, M and Bonzanni, M and Callen, GE and Paster, BJ and Hasturk, H and Ghezzi, CE}, title = {A physiologically relevant culture platform for long-term studies of in vitro gingival tissue.}, journal = {Acta biomaterialia}, volume = {167}, number = {}, pages = {321-334}, pmid = {37331612}, issn = {1878-7568}, support = {R03 DE030224/DE/NIDCR NIH HHS/United States ; }, mesh = {Humans ; *Gingiva/pathology ; *Periodontitis/microbiology/pathology ; Epithelium ; Bacteria ; Biomarkers ; Porphyromonas gingivalis ; }, abstract = {There is a clinical need to understand the etiologies of periodontitis, considering the growing socio-economic impact of the disease. Despite recent advances in oral tissue engineering, experimental approaches have failed to develop a physiologically relevant gingival model that combines tissue organization with salivary flow dynamics and stimulation of the shedding and non-shedding oral surfaces. Herein, we develop a dynamic gingival tissue model composed of a silk scaffold, replicating the cyto-architecture and oxygen profile of the human gingiva, along with a saliva-mimicking medium that reflected the ionic composition, viscosity, and non-Newtonian behavior of human saliva. The construct was cultured in a custom designed bioreactor, in which force profiles on the gingival epithelium were modulated through analysis of inlet position, velocity and vorticity to replicate the physiological shear stress of salivary flow. The gingival bioreactor supported the long-term in vivo features of the gingiva and improved the integrity of the epithelial barrier, critical against the invasion of pathogenic bacteria. Furthermore, the challenge of the gingival tissue with P. gingivalis lipopolysaccharide, as an in vitro surrogate for microbial interactions, indicated a greater stability of the dynamic model in maintaining tissue homeostasis and, thus, its applicability in long-term studies. The model will be integrated into future studies with the human subgingival microbiome to investigate host-pathogen and host-commensal interactions. STATEMENT OF SIGNIFICANCE: The major societal impact of human microbiome had reverberated up to the establishment of the Common Fund's Human Microbiome Project, that has the intent of studying the role of microbial communities in human health and diseases, including periodontitis, atopic dermatitis, or asthma and inflammatory bowel disease. In addition, these chronic diseases are emergent drivers of global socioeconomic status. Not only common oral diseases have been shown to be directly correlated with several systemic conditions, but they are differentially impacting some racial/ethnic and socioeconomic groups. To address this growing social disparity, the development of in vitro gingival model would provide a time and cost-effective experimental platform, able to mimic the spectrum of periodontal disease presentation, for the identification of predictive biomarkers for early-stage diagnosis.}, }
@article {pmid37317128, year = {2023}, author = {Bar, K and Litera-Bar, M and Sozańska, B}, title = {Bacterial Microbiota of Asthmatic Children and Preschool Wheezers' Airways-What Do We Know?.}, journal = {Microorganisms}, volume = {11}, number = {5}, pages = {}, pmid = {37317128}, issn = {2076-2607}, abstract = {Asthma is the most chronic pulmonary disease in pediatric population, and its etiopathology still remains unclear. Both viruses and bacteria are suspected factors of disease development and are responsible for its exacerbation. Since the launch of The Human Microbiome Project, there has been an explosion of research on microbiota and its connection with various diseases. In our review, we have collected recent data about both upper- and lower-airway bacterial microbiota of asthmatic children. We have also included studies regarding preschool wheezers, since asthma diagnosis in children under 5 years of age remains challenging due to the lack of an objective tool. This paper indicates the need for further studies of microbiome and asthma, as in today's knowledge, there is no particular bacterium that discriminates the asthmatics from the healthy peers and can be used as a potential biological factor in the disease prevalence and treatment.}, }
@article {pmid37254222, year = {2023}, author = {Addison, S and Armstrong, C and Wigley, K and Hartley, R and Wakelin, S}, title = {What matters most? Assessment of within-canopy factors influencing the needle microbiome of the model conifer, Pinus radiata.}, journal = {Environmental microbiome}, volume = {18}, number = {1}, pages = {45}, pmid = {37254222}, issn = {2524-6372}, support = {The Tree Microbiome Project: at the root of climate proofing forests (C04X2002)//Ministry of Business, Innovation and Employment/ ; }, abstract = {The assembly and function of the phyllosphere microbiome is important to the overall fitness of plants and, thereby, the ecosystems they inhabit. Presently, model systems for tree phyllosphere microbiome studies are lacking, yet forests resilient to pests, diseases, and climate change are important to support a myriad of ecosystem services impacting from local to global levels. In this study, we extend the development of model microbiome systems for trees species, particularly coniferous gymnosperms, by undertaking a structured approach assessing the phyllosphere microbiome of Pinus radiata. Canopy sampling height was the single most important factor influencing both alpha- and beta-diversity of bacterial and fungal communities (p < 0.005). Bacterial and fungal phyllosphere microbiome richness was lowest in samples from the top of the canopy, subsequently increasing in the middle and then bottom canopy samples. These differences maybe driven by either by (1) exchange of microbiomes with the forest floor and soil with the lower foliage, (2) strong ecological filtering in the upper canopy via environmental exposure (e.g., UV), (3) canopy density, (4) or combinations of factors. Most taxa present in the top canopy were also present lower in tree; as such, sampling strategies focussing on lower canopy sampling should provide good overall phyllosphere microbiome coverage for the tree. The dominant phyllosphere bacteria were Alpha-proteobacteria (Rhizobiales and Sphingomonas) along with Acidobacteria Gp1. However, the P. radiata phyllosphere microbiome samples were fungal dominated. From the top canopy samples, Arthoniomycetes and Dothideomycetes were highly represented, with abundances of Arthoniomycetes then reducing in lower canopy samples whilst abundances of Ascomycota increased. The most abundant fungal taxa were Phaeococcomyces (14.4% of total reads) and Phaeotheca spp. (10.38%). A second-order effect of canopy sampling direction was evident in bacterial community composition (p = 0.01); these directional influences were not evident for fungal communities. However, sterilisation of needles did impact fungal community composition (p = 0.025), indicating potential for community differences in the endosphere versus leaf surface compartments. Needle age was only important in relation to bacterial communities, but was canopy height dependant (interaction p = 0.008). By building an understanding of the primary and secondary factors related to intra-canopy phyllosphere microbiome variation, we provide a sampling framework to either explicitly minimise or capture variation in needle collection to enable ongoing ecological studies targeted at inter-canopy or other experimental levels.}, }
@article {pmid37211280, year = {2023}, author = {Chow, EWL and Pang, LM and Wang, Y}, title = {Impact of the host microbiota on fungal infections: New possibilities for intervention?.}, journal = {Advanced drug delivery reviews}, volume = {198}, number = {}, pages = {114896}, doi = {10.1016/j.addr.2023.114896}, pmid = {37211280}, issn = {1872-8294}, mesh = {Humans ; Antifungal Agents/pharmacology/therapeutic use ; *Mycoses/drug therapy ; Fungi ; *Microbiota ; Bacteria ; }, abstract = {Many human fungal pathogens are opportunistic. They are primarily benign residents of the human body and only become infectious when the host's immunity and microbiome are compromised. Bacteria dominate the human microbiome, playing an essential role in keeping fungi harmless and acting as the first line of defense against fungal infection. The Human Microbiome Project, launched by NIH in 2007, has stimulated extensive investigation and significantly advanced our understanding of the molecular mechanisms governing the interaction between bacteria and fungi, providing valuable insights for developing future antifungal strategies by exploiting the interaction. This review summarizes recent progress in this field and discusses new possibilities and challenges. We must seize the opportunities presented by researching bacterial-fungal interplay in the human microbiome to address the global spread of drug-resistant fungal pathogens and the drying pipelines of effective antifungal drugs.}, }
@article {pmid37195998, year = {2023}, author = {Dai, H and Hou, T and Wang, Q and Hou, Y and Wang, T and Zheng, J and Lin, H and Zhao, Z and Li, M and Wang, S and Zhang, D and Dai, M and Zheng, R and Lu, J and Xu, Y and Chen, Y and Ning, G and Wang, W and Bi, Y and Xu, M}, title = {Causal relationships between the gut microbiome, blood lipids, and heart failure: a Mendelian randomization analysis.}, journal = {European journal of preventive cardiology}, volume = {30}, number = {12}, pages = {1274-1282}, doi = {10.1093/eurjpc/zwad171}, pmid = {37195998}, issn = {2047-4881}, mesh = {Humans ; *Gastrointestinal Microbiome ; Mendelian Randomization Analysis ; Bayes Theorem ; Genome-Wide Association Study ; *Heart Failure ; Apolipoproteins B ; Lipids ; Polymorphism, Single Nucleotide ; }, abstract = {AIMS: Studies have linked gut microbiome and heart failure (HF). However, their causal relationships and potential mediating factors have not been well defined. To investigate the causal relationships between the gut microbiome and HF and the mediating effect of potential blood lipids by using genetics.<br><br>METHODS AND RESULTS: We performed a bidirectional and mediation Mendelian randomization (MR) study using summary statistics from the genome-wide association studies of gut microbial taxa (Dutch Microbiome Project, n = 7738), blood lipids (UK Biobank, n = 115 078), and a meta-analysis of HF (115 150 cases and 1550 331 controls). We applied the inverse-variance weighted estimation method as the primary method, with several other estimators as complementary methods. The multivariable MR approach based on Bayesian model averaging (MR-BMA) was used to prioritize the most likely causal lipids. Six microbial taxa are suggestively associated with HF causally. The most significant taxon was the species Bacteroides dorei [odds ratio = 1.059, 95% confidence interval (CI) = 1.022-1.097, P-value = 0.0017]. The MR-BMA analysis showed that apolipoprotein B (ApoB) was the most likely causal lipid for HF (the marginal inclusion probability = 0.717, P-value = 0.005). The mediation MR analysis showed that ApoB mediated the causal effects of species B. dorei on HF (proportion mediated = 10.1%, 95% CI = 0.2-21.6%, P-value = 0.031).<br><br>CONCLUSION: The study suggested a causal relationship between specific gut microbial taxa and HF and that ApoB might mediate this relationship as the primary lipid determinant of HF.}, }
@article {pmid37195192, year = {2023}, author = {Wang, J and Pan, Z and Yu, J and Zhang, Z and Li, YZ}, title = {Global assembly of microbial communities.}, journal = {mSystems}, volume = {8}, number = {3}, pages = {e0128922}, pmid = {37195192}, issn = {2379-5077}, support = {32070030//National Natural Science Foundation of China (NSFC)/ ; 2018YFA0900400, 2018YFA0901704//MOST | National Key Research and Development Program of China (NKPs)/ ; ZR2022QC229//Science Foundation for Youths of Shandong Province/ ; 2022M711918//China Postdoctoral Science Foundation/ ; SDCX-ZG-20220201//Postdoctoral Innovation Project of Shandong Province ()/ ; 32201303//National Natural Science Foundation of China (NSFC)/ ; }, mesh = {Animals ; *Bacteria/genetics ; *Microbiota/genetics ; Microbial Interactions ; Genes, Bacterial ; Stochastic Processes ; }, abstract = {Different habitats harbor different microbial communities with elusive assembly mechanisms. This study comprehensively investigated the global assembly mechanisms of microbial communities and effects of community-internal influencing factors using the Earth Microbiome Project (EMP) data set. We found that deterministic and stochastic processes contribute approximately equally to global microbial community assembly, and, specifically, deterministic processes generally play a major role in free-living and plant-associated (but not plant corpus) environments, while stochastic processes are the major contributor in animal-associated environments. In contrast with the assembly of microorganisms, the assembly of functional genes, predicted from PICRUSt, is mainly attributed to deterministic processes in all microbial communities. The sink and source microbial communities are normally assembled using similar mechanisms, and the core microorganisms are specific to different environment types. On a global scale, deterministic processes are positively related to the community alpha diversity, microbial interaction degree and bacterial predatory-specific gene abundance. Our analysis provides a panoramic picture and regularities of global and environment-typical microbial community assemblies. IMPORTANCE With the development of sequencing technologies, the research topic of microbial ecology has evolved from the analysis of community composition to community assembly, including the relative contribution of deterministic and stochastic processes for the formation and maintenance of community diversity. Many studies have reported the microbial assembly mechanisms in various habitats, but the assembly regularities of global microbial communities remain unknown. In this study, we analyzed the EMP data set using a combined pipeline to explore the assembly mechanisms of global microbial communities, microbial sources to construct communities, core microbes in different environment types, and community-internal factors influencing assembly. The results provide a panoramic picture and rules of global and environment-typical microbial community assemblies, which enhances our understandings of the mechanisms globally controlling community diversity and species coexistence.}, }
@article {pmid37063923, year = {2023}, author = {Hou, T and Dai, H and Wang, Q and Hou, Y and Zhang, X and Lin, H and Wang, S and Li, M and Zhao, Z and Lu, J and Xu, Y and Chen, Y and Gu, Y and Zheng, J and Wang, T and Wang, W and Bi, Y and Ning, G and Xu, M}, title = {Dissecting the causal effect between gut microbiota, DHA, and urate metabolism: A large-scale bidirectional Mendelian randomization.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1148591}, pmid = {37063923}, issn = {1664-3224}, mesh = {Humans ; Docosahexaenoic Acids ; *Gastrointestinal Microbiome ; *Gout/genetics ; Mendelian Randomization Analysis ; Uric Acid ; }, abstract = {OBJECTIVES: Our aim was to investigate the interactive causal effects between gut microbiota and host urate metabolism and explore the underlying mechanism using genetic methods.<br><br>METHODS: We extracted summary statistics from the abundance of 211 microbiota taxa from the MiBioGen (N =18,340), 205 microbiota metabolism pathways from the Dutch Microbiome Project (N =7738), gout from the Global Biobank Meta-analysis Initiative (N =1,448,128), urate from CKDGen (N =288,649), and replication datasets from the Global Urate Genetics Consortium (N gout =69,374; N urate =110,347). We used linkage disequilibrium score regression and bidirectional Mendelian randomization (MR) to detect genetic causality between microbiota and gout/urate. Mediation MR and colocalization were performed to investigate potential mediators in the association between microbiota and urate metabolism.<br><br>RESULTS: Two taxa had a common causal effect on both gout and urate, whereas the Victivallaceae family was replicable. Six taxa were commonly affected by both gout and urate, whereas the Ruminococcus gnavus group genus was replicable. Genetic correlation supported significant results in MR. Two microbiota metabolic pathways were commonly affected by gout and urate. Mediation analysis indicated that the Bifidobacteriales order and Bifidobacteriaceae family had protective effects on urate mediated by increasing docosahexaenoic acid. These two bacteria shared a common causal variant rs182549 with both docosahexaenoic acid and urate, which was located within MCM6/LCT locus.<br><br>CONCLUSIONS: Gut microbiota and host urate metabolism had a bidirectional causal association, implicating the critical role of host-microbiota crosstalk in hyperuricemic patients. Changes in gut microbiota can not only ameliorate host urate metabolism but also become a foreboding indicator of urate metabolic diseases.}, }
@article {pmid37017243, year = {2023}, author = {Dilmore, AH and Martino, C and Neth, BJ and West, KA and Zemlin, J and Rahman, G and Panitchpakdi, M and Meehan, MJ and Weldon, KC and Blach, C and Schimmel, L and Kaddurah-Daouk, R and Dorrestein, PC and Knight, R and Craft, S and , }, title = {Effects of a ketogenic and low-fat diet on the human metabolome, microbiome, and foodome in adults at risk for Alzheimer's disease.}, journal = {Alzheimer's &amp; dementia : the journal of the Alzheimer's Association}, volume = {19}, number = {11}, pages = {4805-4816}, pmid = {37017243}, issn = {1552-5279}, support = {R01 AG046171/AG/NIA NIH HHS/United States ; U24 AG021886/AG/NIA NIH HHS/United States ; U19 AG063744/AG/NIA NIH HHS/United States ; RF1 AG059093/AG/NIA NIH HHS/United States ; /NH/NIH HHS/United States ; U01 AG061359/AG/NIA NIH HHS/United States ; RF1 AG057452/AG/NIA NIH HHS/United States ; P30 AG072947/AG/NIA NIH HHS/United States ; RF1 AG051550/AG/NIA NIH HHS/United States ; RF1 AG0151550/AG/NIA NIH HHS/United States ; }, mesh = {United States ; Humans ; Adult ; *Alzheimer Disease/metabolism ; Diet, Fat-Restricted ; *Microbiota ; Metabolome/physiology ; Seizures ; Ketone Bodies ; gamma-Aminobutyric Acid/metabolism ; }, abstract = {INTRODUCTION: The ketogenic diet (KD) is an intriguing therapeutic candidate for Alzheimer's disease (AD) given its protective effects against metabolic dysregulation and seizures. Gut microbiota are essential for KD-mediated neuroprotection against seizures as well as modulation of bile acids, which play a major role in cholesterol metabolism. These relationships motivated our analysis of gut microbiota and metabolites related to cognitive status following a controlled KD intervention compared with a low-fat-diet intervention.<br><br>METHODS: Prediabetic adults, either with mild cognitive impairment (MCI) or cognitively normal (CN), were placed on either a low-fat American Heart Association diet or high-fat modified Mediterranean KD (MMKD) for 6 weeks; then, after a 6-week washout period, they crossed over to the alternate diet. We collected stool samples for shotgun metagenomics and untargeted metabolomics at five time points to investigate individuals' microbiome and metabolome throughout the dietary interventions.<br><br>RESULTS: Participants with MCI on the MMKD had lower levels of GABA-producing microbes Alistipes sp. CAG:514 and GABA, and higher levels of GABA-regulating microbes Akkermansia muciniphila. MCI individuals with curcumin in their diet had lower levels of bile salt hydrolase-containing microbes and an altered bile acid pool, suggesting reduced gut motility.<br><br>DISCUSSION: Our results suggest that the MMKD may benefit adults with MCI through modulation of GABA levels and gut-transit time.}, }
@article {pmid36973807, year = {2023}, author = {Zhang, Y and Wang, Y and Tang, M and Zhou, J and Zhang, T}, title = {The microbial dark matter and "wanted list" in worldwide wastewater treatment plants.}, journal = {Microbiome}, volume = {11}, number = {1}, pages = {59}, pmid = {36973807}, issn = {2049-2618}, mesh = {Sewage ; Wastewater ; RNA, Ribosomal, 16S/genetics/analysis ; *Microbiota/genetics ; *Water Purification ; }, abstract = {BACKGROUND: Wastewater treatment plants (WWTPs) are one of the largest biotechnology applications in the world and are of critical importance to modern urban societies. An accurate evaluation of the microbial dark matter (MDM, microorganisms whose genomes remain uncharacterized) proportions in WWTPs is of great value, while there is no such research yet. This study conducted a global meta-analysis of MDM in WWTPs with 317,542 prokaryotic genomes from the Genome Taxonomy Database and proposed a "wanted list" for priority targets in further investigations of activated sludge.<br><br>RESULTS: Compared with the Earth Microbiome Project data, WWTPs had relatively lower genome-sequenced proportions of prokaryotes than other ecosystems, such as the animal related environments. Analysis showed that the median proportions of the genome-sequenced cells and taxa (100% identity and 100% coverage in 16S rRNA gene region) in WWTPs reached 56.3% and 34.5% for activated sludge, 48.6% and 28.5% for aerobic biofilm, and 48.3% and 28.5% for anaerobic digestion sludge, respectively. This result meant MDM had high proportions in WWTPs. Besides, all of the samples were occupied by a few predominant taxa, and the majority of the sequenced genomes were from pure cultures. The global-scale "wanted list" for activated sludge contained four phyla that have few representatives and 71 operational taxonomic units with the majority of them having no genome or isolate yet. Finally, several genome mining methods were verified to successfully recover genomes from activated sludge such as hybrid assembly of the second- and third-generation sequencing.<br><br>CONCLUSIONS: This work elucidated the proportion of MDM in WWTPs, defined the "wanted list" of activated sludge for future investigations, and certified potential genome recovery methods. The proposed methodology of this study can be applied to other ecosystems and improve understanding of ecosystem structure across diverse habitats. Video Abstract.}, }
@article {pmid36966280, year = {2023}, author = {Zhao, Y and Yi, J and Xiang, J and Jia, W and Chen, A and Chen, L and Zheng, L and Zhou, W and Wu, M and Yu, Z and Tang, J}, title = {Exploration of lung mycobiome in the patients with non-small-cell lung cancer.}, journal = {BMC microbiology}, volume = {23}, number = {1}, pages = {81}, pmid = {36966280}, issn = {1471-2180}, mesh = {Humans ; *Mycobiome ; *Carcinoma, Non-Small-Cell Lung ; Fungi/genetics ; *Lung Neoplasms ; Lung ; }, abstract = {As the Human Microbiome Project (HMP) progresses, the relationship between microbes and human health has been receiving increasing attention. A growing number of reports support the correlation between cancer and microbes. However, most studies have focused on bacteria, rather than fungal communities. In this study, we studied the alteration in lung mycobiome in patients with non-small-cell lung cancer (NSCLC) using metagenomic sequencing and qPCR. The higher fungal diversity and more complex network were observed in the patients with NSCLC. In addition, Alternaria arborescens was found as the most relevant fungus to NSCLC, and the enrichment of it in cancerous tissue was also detected. This study proposes that the changes in fungal communities may be closely related to lung cancer, and provides insights into further exploration the relationship between lung cancer and fungi.}, }
@article {pmid36943054, year = {2023}, author = {Zhou, C and Wang, Y and Li, C and Xie, Z and Dai, L}, title = {Amelioration of Colitis by a Gut Bacterial Consortium Producing Anti-Inflammatory Secondary Bile Acids.}, journal = {Microbiology spectrum}, volume = {11}, number = {2}, pages = {e0333022}, pmid = {36943054}, issn = {2165-0497}, abstract = {The Integrative Human Microbiome Project and other cohort studies have indicated that inflammatory bowel disease is accompanied by dysbiosis of gut microbiota, decreased production of secondary bile acids, and increased levels of primary bile acids. Secondary bile acids, such as ursodeoxycholic acid (UDCA) and lithocholic acid (LCA), have been reported to be anti-inflammatory, yet it remains to be studied whether introducing selected bacteria strains to restore bile acid metabolism of the gut microbiome can alleviate intestinal inflammation. In this study, we screened human gut bacterial strains for bile acid metabolism and designed a consortium of three species, including Clostridium AP sp000509125, Bacteroides ovatus, and Eubacterium limosum, and named it BAC (bile acid consortium). We showed that the three-strain gut bacterial consortium BAC is capable of converting conjugated primary bile acids taurochenodeoxycholic acid and glycochenodeoxycholic acid to secondary bile acids UDCA and LCA in vitro. Oral gavage treatment with BAC in mice resulted in protective effects against dextran sulfate sodium (DSS)-induced colitis, including reduced weight loss and increased colon length. Furthermore, BAC treatment increased the fecal level of bile acids, including UDCA and LCA. BAC treatment enhanced intestinal barrier function, which may be attributed to the increased activation of the bile acid receptor TGR5 by secondary bile acids. Finally, we examined the remodeling of gut microbiota by BAC treatment. Taken together, the three-strain gut bacterial consortium BAC restored the dysregulated bile acid metabolism and alleviated DSS-induced colitis. Our study provides a proof-of-concept demonstration that a rationally designed bacterial consortium can reshape the metabolism of the gut microbiome to treat diseases. IMPORTANCE Secondary bile acids have been reported to be anti-inflammatory, yet it remains to be studied whether introducing selected bacteria strains to restore bile acid metabolism of the gut microbiome can alleviate intestinal inflammation. To address this gap, we designed a consortium of human gut bacterial strains based on their metabolic capacity to produce secondary bile acids UDCA and LCA, and we evaluated the efficacy of single bacterial strains and the bacterial consortium in treating the murine colitis model. We found that oral gavage of the bacterial consortium to mice restored secondary bile acid metabolism to increase levels of UDCA and LCA, which induced the activation of TGR5 to improve gut-barrier integrity and reduced the inflammation in murine colitis. Overall, our study demonstrates that rationally designed bacterial consortia can reshape the metabolism of the gut microbiome and provides novel insights into the application of live biotherapeutics for treating IBD.}, }
@article {pmid36929933, year = {2023}, author = {Zou, H and Sun, T and Jin, B and Wang, S}, title = {sBGC-hm: an atlas of secondary metabolite biosynthetic gene clusters from the human gut microbiome.}, journal = {Bioinformatics (Oxford, England)}, volume = {39}, number = {3}, pages = {}, pmid = {36929933}, issn = {1367-4811}, mesh = {Humans ; *Gastrointestinal Microbiome/genetics ; *Microbiota ; Multigene Family ; Biosynthetic Pathways/genetics ; }, abstract = {SUMMARY: Microbial secondary metabolites exhibit potential medicinal value. A large number of secondary metabolite biosynthetic gene clusters (BGCs) in the human gut microbiome, which exhibit essential biological activity in microbe-microbe and microbe-host interactions, have not been adequately characterized, making it difficult to prioritize these BGCs for experimental characterization. Here, we present the sBGC-hm, an atlas of secondary metabolite BGCs allows researchers to explore the potential therapeutic benefits of these natural products. One of its key features is the ability to assist in optimizing the BGC structure by utilizing the gene co-occurrence matrix obtained from Human Microbiome Project data. Results are viewable online and can be downloaded as spreadsheets.<br><br>The database is openly available at https://www.wzubio.com/sbgc. The website is powered by Apache 2 server with PHP and MariaDB.}, }
@article {pmid36928026, year = {2023}, author = {Seymour, CO and Palmer, M and Becraft, ED and Stepanauskas, R and Friel, AD and Schulz, F and Woyke, T and Eloe-Fadrosh, E and Lai, D and Jiao, JY and Hua, ZS and Liu, L and Lian, ZH and Li, WJ and Chuvochina, M and Finley, BK and Koch, BJ and Schwartz, E and Dijkstra, P and Moser, DP and Hungate, BA and Hedlund, BP}, title = {Hyperactive nanobacteria with host-dependent traits pervade Omnitrophota.}, journal = {Nature microbiology}, volume = {8}, number = {4}, pages = {727-744}, pmid = {36928026}, issn = {2058-5276}, support = {1826734//National Science Foundation (NSF)/ ; 1928924//National Science Foundation (NSF)/ ; 1516679//National Science Foundation (NSF)/ ; }, mesh = {Humans ; *Calcifying Nanoparticles/metabolism ; Bacteria/metabolism ; *Microbiota/genetics ; }, abstract = {Candidate bacterial phylum Omnitrophota has not been isolated and is poorly understood. We analysed 72 newly sequenced and 349 existing Omnitrophota genomes representing 6 classes and 276 species, along with Earth Microbiome Project data to evaluate habitat, metabolic traits and lifestyles. We applied fluorescence-activated cell sorting and differential size filtration, and showed that most Omnitrophota are ultra-small (~0.2 μm) cells that are found in water, sediments and soils. Omnitrophota genomes in 6 classes are reduced, but maintain major biosynthetic and energy conservation pathways, including acetogenesis (with or without the Wood-Ljungdahl pathway) and diverse respirations. At least 64% of Omnitrophota genomes encode gene clusters typical of bacterial symbionts, suggesting host-associated lifestyles. We repurposed quantitative stable-isotope probing data from soils dominated by andesite, basalt or granite weathering and identified 3 families with high isotope uptake consistent with obligate bacterial predators. We propose that most Omnitrophota inhabit various ecosystems as predators or parasites.}, }
@article {pmid36910167, year = {2023}, author = {Zhao, J and Rodriguez, J and Martens-Habbena, W}, title = {Fine-scale evaluation of two standard 16S rRNA gene amplicon primer pairs for analysis of total prokaryotes and archaeal nitrifiers in differently managed soils.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1140487}, pmid = {36910167}, issn = {1664-302X}, abstract = {The advance of high-throughput molecular biology tools allows in-depth profiling of microbial communities in soils, which possess a high diversity of prokaryotic microorganisms. Amplicon-based sequencing of 16S rRNA genes is the most common approach to studying the richness and composition of soil prokaryotes. To reliably detect different taxonomic lineages of microorganisms in a single soil sample, an adequate pipeline including DNA isolation, primer selection, PCR amplification, library preparation, DNA sequencing, and bioinformatic post-processing is required. Besides DNA sequencing quality and depth, the selection of PCR primers and PCR amplification reactions arguably have the largest influence on the results. This study tested the performance and potential bias of two primer pairs, i.e., 515F (Parada)-806R (Apprill) and 515F (Parada)-926R (Quince) in the standard pipelines of 16S rRNA gene Illumina amplicon sequencing protocol developed by the Earth Microbiome Project (EMP), against shotgun metagenome-based 16S rRNA gene reads. The evaluation was conducted using five differently managed soils. We observed a higher richness of soil total prokaryotes by using reverse primer 806R compared to 926R, contradicting to in silico evaluation results. Both primer pairs revealed various degrees of taxon-specific bias compared to metagenome-derived 16S rRNA gene reads. Nonetheless, we found consistent patterns of microbial community variation associated with different land uses, irrespective of primers used. Total microbial communities, as well as ammonia oxidizing archaea (AOA), the predominant ammonia oxidizers in these soils, shifted along with increased soil pH due to agricultural management. In the unmanaged low pH plot abundance of AOA was dominated by the acid-tolerant NS-Gamma clade, whereas limed agricultural plots were dominated by neutral-alkaliphilic NS-Delta/NS-Alpha clades. This study stresses how primer selection influences community composition and highlights the importance of primer selection for comparative and integrative studies, and that conclusions must be drawn with caution if data from different sequencing pipelines are to be compared.}, }
@article {pmid36838283, year = {2023}, author = {Morrison, AG and Sarkar, S and Umar, S and Lee, STM and Thomas, SM}, title = {The Contribution of the Human Oral Microbiome to Oral Disease: A Review.}, journal = {Microorganisms}, volume = {11}, number = {2}, pages = {}, pmid = {36838283}, issn = {2076-2607}, support = {P30 CA168524/CA/NCI NIH HHS/United States ; }, abstract = {The oral microbiome is an emerging field that has been a topic of discussion since the development of next generation sequencing and the implementation of the human microbiome project. This article reviews the current literature surrounding the oral microbiome, briefly highlighting most recent methods of microbiome characterization including cutting edge omics, databases for the microbiome, and areas with current gaps in knowledge. This article also describes reports on microorganisms contained in the oral microbiome which include viruses, archaea, fungi, and bacteria, and provides an in-depth analysis of their significant roles in tissue homeostasis. Finally, we detail key bacteria involved in oral disease, including oral cancer, and the current research surrounding their role in stimulation of inflammatory cytokines, the role of gingival crevicular fluid in periodontal disease, the creation of a network of interactions between microorganisms, the influence of the planktonic microbiome and cospecies biofilms, and the implications of antibiotic resistance. This paper provides a comprehensive literature analysis while also identifying gaps in knowledge to enable future studies to be conducted.}, }
@article {pmid36770726, year = {2023}, author = {Zhang, MN and Xie, R and Wang, HG and Wen, X and Wang, JY and He, L and Zhang, MH and Yang, XZ}, title = {Cepharanthine Alleviates DSS-Induced Ulcerative Colitis via Regulating Aconitate Decarboxylase 1 Expression and Macrophage Infiltration.}, journal = {Molecules (Basel, Switzerland)}, volume = {28}, number = {3}, pages = {}, pmid = {36770726}, issn = {1420-3049}, mesh = {Animals ; Mice ; Humans ; *Colitis, Ulcerative/chemically induced/drug therapy/metabolism ; Macrophages ; Colon/metabolism ; *Benzylisoquinolines/pharmacology ; Dextran Sulfate/toxicity ; Disease Models, Animal ; *Colitis/metabolism ; Mice, Inbred C57BL ; }, abstract = {Cepharanthine (CEP), a bisbenzylisoquinoline alkaloid from tubers of Stephania, protects against some inflammatory diseases. Aconitate decarboxylase 1 (ACOD1) is also known as immune-responsive gene 1 (IRG1), which plays an important immunometabolism role in inflammatory diseases by mediating the production of itaconic acid. ACOD1 exhibits abnormal expression in ulcerative colitis (UC). However, whether CEP can combat UC by affecting ACOD1 expression remains unanswered. This study was designed to explore the protective effects and mechanisms of CEP in treating colitis through in vitro and in vivo experiments. In vitro assays indicated that CEP inhibited LPS-induced secretion of pro-inflammatory cytokines and ACOD1 expression in RAW264.7 macrophages. Additionally, in the mouse model of DSS-induced colitis, CEP decreased macrophage infiltration and ACOD1 expression in colon tissue. After treatment with antibiotics (Abx), the expression of ACOD1 changed with the composition of gut microbiota. Correlation analysis also revealed that Family-XIII-AD3011-group and Rumini-clostridium-6 were positively correlated with ACOD1 expression level. Additionally, data of the integrative Human Microbiome Project (iHMP) showed that ACOD1 was highly expressed in the colon tissue of UC patients and this expression was positively correlated with the severity of intestinal inflammation. Collectively, CEP can counter UC by modulating gut microbiota and inhibiting the expression of ACOD1. CEP may serve as a potential pharmaceutical candidate in the treatment of UC.}, }
@article {pmid36675055, year = {2023}, author = {Kustrimovic, N and Bombelli, R and Baci, D and Mortara, L}, title = {Microbiome and Prostate Cancer: A Novel Target for Prevention and Treatment.}, journal = {International journal of molecular sciences}, volume = {24}, number = {2}, pages = {}, pmid = {36675055}, issn = {1422-0067}, mesh = {Male ; Humans ; *Microbiota/physiology ; *Prostatic Neoplasms/therapy/pathology ; *Gastrointestinal Microbiome/physiology ; Prostate/pathology ; Inflammation ; Dysbiosis ; }, abstract = {Growing evidence of the microbiome's role in human health and disease has emerged since the creation of the Human Microbiome Project. Recent studies suggest that alterations in microbiota composition (dysbiosis) may play an essential role in the occurrence, development, and prognosis of prostate cancer (PCa), which remains the second most frequent male malignancy worldwide. Current advances in biological technologies, such as high-throughput sequencing, transcriptomics, and metabolomics, have enabled research on the gut, urinary, and intra-prostate microbiome signature and the correlation with local and systemic inflammation, host immunity response, and PCa progression. Several microbial species and their metabolites facilitate PCa insurgence through genotoxin-mediated mutagenesis or by driving tumor-promoting inflammation and dysfunctional immunosurveillance. However, the impact of the microbiome on PCa development, progression, and response to treatment is complex and needs to be fully understood. This review addresses the current knowledge on the host-microbe interaction and the risk of PCa, providing novel insights into the intraprostatic, gut, and urinary microbiome mechanisms leading to PCa carcinogenesis and treatment response. In this paper, we provide a detailed overview of diet changes, gut microbiome, and emerging therapeutic approaches related to the microbiome and PCa. Further investigation on the prostate-related microbiome and large-scale clinical trials testing the efficacy of microbiota modulation approaches may improve patient outcomes while fulfilling the literature gap of microbial-immune-cancer-cell mechanistic interactions.}, }
@article {pmid36655544, year = {2023}, author = {Sun, H and Wang, P and Li, Y}, title = {An integrated microbiome project for charactering microbial diversity in classroom based on virtual simulation experiments.}, journal = {Biochemistry and molecular biology education : a bimonthly publication of the International Union of Biochemistry and Molecular Biology}, volume = {51}, number = {2}, pages = {171-179}, doi = {10.1002/bmb.21706}, pmid = {36655544}, issn = {1539-3429}, mesh = {Humans ; RNA, Ribosomal, 16S/genetics ; *Learning ; Students ; Computational Biology/education ; *Microbiota/genetics ; }, abstract = {Microbiome study requires both molecular techniques and bioinformatics skills, which are challenging for biologists to participate in this growing field. To introduce microbiome concepts and skills to students, a 6-week wet-lab and bioinformatics course for undergraduates was implemented through the project-based learning (PBL) approach. In the saliva microbiome project, students collected their saliva samples, performed DNA extraction and PCR amplification, followed by metagenomic analysis to compare the diversity and abundances of microbes among samples. First, students are required to practice molecular techniques and bioinformatics analysis skills in a virtual simulation lab. To our knowledge, our study is the first one to incorporate a virtual lab into microbiome experience. Then, students applied their recently acquired skills to produce and analyze their own 16S amplicon sequencing data and reported their results via a scientific report. The student learning outcomes show that the Virtual lab can improve students' laboratory techniques and research capabilities. Moreover, a simple pipeline to analyze 16S rRNA gene amplicon sequencing data is introduced in a step-by-step manner that helps students to develop analysis skills. This project can be modified as either a virtual course or a module within another course such as microbiology, molecular biology, and bioinformatics. Our study provides evidence on the positive impact of virtual labs on learning outcomes in undergraduate science education.}, }
@article {pmid36612415, year = {2022}, author = {Eggers, S and Bixby, M and Renzetti, S and Curtin, P and Gennings, C}, title = {Human Microbiome Mixture Analysis Using Weighted Quantile Sum Regression.}, journal = {International journal of environmental research and public health}, volume = {20}, number = {1}, pages = {}, pmid = {36612415}, issn = {1660-4601}, support = {U2C ES026555/ES/NIEHS NIH HHS/United States ; K99 ES032884/ES/NIEHS NIH HHS/United States ; P30 ES023515/ES/NIEHS NIH HHS/United States ; T32 HD049311/HD/NICHD NIH HHS/United States ; U2CES026555/ES/NIEHS NIH HHS/United States ; P30ES023515/ES/NIEHS NIH HHS/United States ; }, mesh = {Humans ; Feces ; *Microbiota ; *Gastrointestinal Microbiome ; Obesity ; Body Mass Index ; }, abstract = {Studies of the health effects of the microbiome often measure overall associations by using diversity metrics, and individual taxa associations in separate analyses, but do not consider the correlated relationships between taxa in the microbiome. In this study, we applied random subset weighted quantile sum regression with repeated holdouts (WQSRSRH), a mixture method successfully applied to 'omic data to account for relationships between many predictors, to processed amplicon sequencing data from the Human Microbiome Project. We simulated a binary variable associated with 20 operational taxonomic units (OTUs). WQSRSRH was used to test for the association between the microbiome and the simulated variable, adjusted for sex, and sensitivity and specificity were calculated. The WQSRSRH method was also compared to other standard methods for microbiome analysis. The method was further illustrated using real data from the Growth and Obesity Cohort in Chile to assess the association between the gut microbiome and body mass index. In the analysis with simulated data, WQSRSRH predicted the correct directionality of association between the microbiome and the simulated variable, with an average sensitivity and specificity of 75% and 70%, respectively, in identifying the 20 associated OTUs. WQSRSRH performed better than all other comparison methods. In the illustration analysis of the gut microbiome and obesity, the WQSRSRH analysis identified an inverse association between body mass index and the gut microbe mixture, identifying Bacteroides, Clostridium, Prevotella, and Ruminococcus as important genera in the negative association. The application of WQSRSRH to the microbiome allows for analysis of the mixture effect of all the taxa in the microbiome, while simultaneously identifying the most important to the mixture, and allowing for covariate adjustment. It outperformed other methods when using simulated data, and in analysis with real data found results consistent with other study findings.}, }
@article {pmid36566203, year = {2022}, author = {Dang, T and Kumaishi, K and Usui, E and Kobori, S and Sato, T and Toda, Y and Yamasaki, Y and Tsujimoto, H and Ichihashi, Y and Iwata, H}, title = {Stochastic variational variable selection for high-dimensional microbiome data.}, journal = {Microbiome}, volume = {10}, number = {1}, pages = {236}, pmid = {36566203}, issn = {2049-2618}, mesh = {Humans ; Bayes Theorem ; Algorithms ; *Microbiota/genetics ; *Gastrointestinal Microbiome/genetics ; Metagenomics ; }, abstract = {BACKGROUND: The rapid and accurate identification of a minimal-size core set of representative microbial species plays an important role in the clustering of microbial community data and interpretation of clustering results. However, the huge dimensionality of microbial metagenomics datasets is a major challenge for the existing methods such as Dirichlet multinomial mixture (DMM) models. In the approach of the existing methods, the computational burden of identifying a small number of representative species from a large number of observed species remains a challenge.<br><br>RESULTS: We propose a novel approach to improve the performance of the widely used DMM approach by combining three ideas: (i) we propose an indicator variable to identify representative operational taxonomic units that substantially contribute to the differentiation among clusters; (ii) to address the computational burden of high-dimensional microbiome data, we propose a stochastic variational inference, which approximates the posterior distribution using a controllable distribution called variational distribution, and stochastic optimization algorithms for fast computation; and (iii) we extend the finite DMM model to an infinite case by considering Dirichlet process mixtures and estimating the number of clusters as a variational parameter. Using the proposed method, stochastic variational variable selection (SVVS), we analyzed the root microbiome data collected in our soybean field experiment, the human gut microbiome data from three published datasets of large-scale case-control studies and the healthy human microbiome data from the Human Microbiome Project.<br><br>CONCLUSIONS: SVVS demonstrates a better performance and significantly faster computation than those of the existing methods in all cases of testing datasets. In particular, SVVS is the only method that can analyze massive high-dimensional microbial data with more than 50,000 microbial species and 1000 samples. Furthermore, a core set of representative microbial species is identified using SVVS that can improve the interpretability of Bayesian mixture models for a wide range of microbiome studies. Video Abstract.}, }
@article {pmid36566099, year = {2023}, author = {Mishra, K and Isali, I and Sindhani, M and Prunty, M and Bell, S and Mahran, A and Damiani, G and Ghannoum, M and Retuerto, M and Kutikov, A and Ross, J and Woo, LL and Abbosh, PH and Bukavina, L}, title = {Characterization of Changes in Penile Microbiome Following Pediatric Circumcision.}, journal = {European urology focus}, volume = {9}, number = {4}, pages = {669-680}, doi = {10.1016/j.euf.2022.12.007}, pmid = {36566099}, issn = {2405-4569}, mesh = {United States ; Male ; Infant ; Humans ; Child ; Phylogeny ; *Gastrointestinal Microbiome ; *Microbiota/genetics ; *Mycobiome ; Inflammation ; }, abstract = {BACKGROUND: While microbiome and host regulation contribute independently to many disease states, it is unclear how circumcision in pediatric population influences subsequent changes in penile microbiome.<br><br>OBJECTIVE: Our study aims to analyze jointly paired taxonomic profiles and assess pathways implicated in inflammation, barrier protection, and energy metabolism.<br><br>We analyzed 11 paired samples, periurethral collection, before and after circumcision, to generate microbiome and mycobiome profiling. Sample preparation of 16S ribosomal RNA and internal transcribed spacer sequencing was adapted from the methods developed by the National Institutes of Health Human Microbiome Project.<br><br>We obtained the predictive functional attributes of the microbial communities between samples using Silva-Tax4Fun and the Greengenes-Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) approach. The predictive functioning of the microbial communities was determined by linearly combining the normalized taxonomic abundances into the precomputed association matrix of Kyoto Encyclopedia of Genes and Genomes orthology reference profiles.<br><br>RESULTS AND LIMITATIONS: Several notable microbiome and mycobiome compositional differences were observed between pre- and postcircumcision patients. Pairwise comparisons across taxa revealed a significant decrease (p&#xa0;<&#xa0;0.05, false discovery rate corrected) of microbiome organisms (Clostridiales, Bacteroidales, and Campylobacterales) and mycobiome (Saccharomycetales and Pleosporales) following circumcision. A total of 14 pathways were found to differ in abundance between the pre- and postcircumcision groups (p&#xa0;<&#xa0;0.005, false discovery rate <0.1 and linear discriminant analysis score >3; five enriched and nine depleted). The pathways reduced after circumcision were mostly involved with amino acid and glucose metabolism, while pathways prior to circumcision were enriched in genetic information processing and transcription processes. As expected, enrichment in methyl-accepting chemotaxis protein, an integral membrane protein involved in directed motility of microbes to chemical cues and environment, occurred prior to circumcision, while the filamentous hemagglutinin pathway (a strong immunogenic protein) was depleted after circumcision CONCLUSIONS: Our results offer greater insight into the host-microbiota relationship of penile circumcision and may serve to lay the groundwork for future studies focused on drivers of inflammation, infection, and oncogenesis.<br><br>PATIENT SUMMARY: Our study showed a significant reduction in bacteria and fungi after circumcision, particularly anaerobic bacteria, which are known to be potential inducers of inflammation and cancer. This is the first study of its kind showing the changes in microbiome after circumcision, and some of the changes that occur in healthy infants after circumcision that may explain the differences in cancer and inflammatory disorders in adulthood.}, }
@article {pmid36557564, year = {2022}, author = {Bruno, A and Fumagalli, S and Ghisleni, G and Labra, M}, title = {The Microbiome of the Built Environment: The Nexus for Urban Regeneration for the Cities of Tomorrow.}, journal = {Microorganisms}, volume = {10}, number = {12}, pages = {}, pmid = {36557564}, issn = {2076-2607}, support = {H43C22000550001//Ministry of Education, Universities and Research/ ; }, abstract = {Built environments are, for most of us, our natural habitat. In the last 50 years, the built-up area has more than doubled, with a massive biodiversity loss. The undeniable benefits of a city providing all the basic needs to a growing population showed longer-term and less obvious costs to human health: autoimmune and non-communicable diseases, as well as antimicrobial resistance, have reached unprecedented and alarming levels. Humans coevolved with microbes, and this long-lasting alliance is affected by the loss of connection with natural environments, misuse of antibiotics, and highly sanitized environments. Our aim is to direct the focus onto the microbial communities harbored by the built environments we live in. They represent the nexus for urban regeneration, which starts from a healthy environment. Planning a city means considering, in a two-fold way, the ecosystem health and the multidimensional aspects of wellbeing, including social, cultural, and aesthetic values. The significance of this perspective is inspiring guidelines and strategies for the urban regeneration of the cities of tomorrow, exploiting the invaluable role of microbial biodiversity and the ecosystem services that it could provide to create the robust scientific knowledge that is necessary for a bioinformed design of buildings and cities for healthy and sustainable living.}, }
@article {pmid36534203, year = {2022}, author = {Jesus, HNR and Ramos, JN and Rocha, DJPG and Alves, DA and Silva, CS and Cruz, JVO and Vieira, VV and Souza, C and Santos, LS and Navas, J and Ramos, RTJ and Azevedo, V and Aguiar, ERGR and Mattos-Guaraldi, AL and Pacheco, LGC}, title = {The pan-genome of the emerging multidrug-resistant pathogen Corynebacterium striatum.}, journal = {Functional &amp; integrative genomics}, volume = {23}, number = {1}, pages = {5}, pmid = {36534203}, issn = {1438-7948}, support = {BOL0505/2018//Funda&#xe7;&#xe3;o de Amparo &#xe0; Pesquisa do Estado da Bahia/ ; BOL0505/2018//Funda&#xe7;&#xe3;o de Amparo &#xe0; Pesquisa do Estado da Bahia/ ; CAPES-PROCAD 071/2013//Coordena&#xe7;&#xe3;o de Aperfei&#xe7;oamento de Pessoal de N&#xed;vel Superior/ ; CAPES-PROCAD 071/2013//Coordena&#xe7;&#xe3;o de Aperfei&#xe7;oamento de Pessoal de N&#xed;vel Superior/ ; CAPES-PROCAD 071/2013//Coordena&#xe7;&#xe3;o de Aperfei&#xe7;oamento de Pessoal de N&#xed;vel Superior/ ; CAPES-PROCAD 071/2013//Coordena&#xe7;&#xe3;o de Aperfei&#xe7;oamento de Pessoal de N&#xed;vel Superior/ ; CAPES-PROCAD 071/2013//Coordena&#xe7;&#xe3;o de Aperfei&#xe7;oamento de Pessoal de N&#xed;vel Superior/ ; CAPES-PROCAD 071/2013//Coordena&#xe7;&#xe3;o de Aperfei&#xe7;oamento de Pessoal de N&#xed;vel Superior/ ; CNPq N&#xba; 09/2018//Conselho Nacional de Desenvolvimento Cient&#xed;fico e Tecnol&#xf3;gico/ ; CNPq N&#xba; 09/2018//Conselho Nacional de Desenvolvimento Cient&#xed;fico e Tecnol&#xf3;gico/ ; CNPq N&#xba; 09/2018//Conselho Nacional de Desenvolvimento Cient&#xed;fico e Tecnol&#xf3;gico/ ; MCT/FINEP/CT-INFRA01/2013//Financiadora de Estudos e Projetos/ ; }, mesh = {Humans ; *Corynebacterium ; *Anti-Bacterial Agents ; Phenotype ; Virulence Factors/genetics ; Drug Resistance, Multiple, Bacterial/genetics ; Microbial Sensitivity Tests ; }, abstract = {Corynebacterium striatum, a common constituent of the human skin microbiome, is now considered an emerging multidrug-resistant pathogen of immunocompromised and chronically ill patients. However, little is known about the molecular mechanisms in the transition from colonization to the multidrug-resistant (MDR) invasive phenotype in clinical isolates. This study performed a comprehensive pan-genomic analysis of C. striatum, including isolates from "normal skin microbiome" and from MDR infections, to gain insights into genetic factors contributing to pathogenicity and multidrug resistance in this species. For this, three novel genome sequences were obtained from clinical isolates of C. striatum of patients from Brazil, and other 24 complete or draft C. striatum genomes were retrieved from GenBank, including the ATCC6940 isolate from the Human Microbiome Project. Analysis of C. striatum strains demonstrated the presence of an open pan-genome (α = 0.852803) containing 3816 gene families, including 15 antimicrobial resistance (AMR) genes and 32 putative virulence factors. The core and accessory genomes included 1297 and 1307 genes, respectively. The identified AMR genes are primarily associated with resistance to aminoglycosides and tetracyclines. Of these, 66.6% are present in genomic islands, and four AMR genes, including aac(6')-ib7, are located in a class 1-integron. In conclusion, our data indicated that C. striatum possesses genomic characteristics favorable to the invasive phenotype, with high genomic plasticity, a robust genetic arsenal for iron acquisition, and important virulence determinants and AMR genes present in mobile genetic elements.}, }
@article {pmid36453887, year = {2022}, author = {Zhang, W and Han, N and Zhang, T and Qiang, Y and Peng, X and Li, X and Kan, B}, title = {The Spatial Features and Temporal Changes in the Gut Microbiota of a Healthy Chinese Population.}, journal = {Microbiology spectrum}, volume = {10}, number = {6}, pages = {e0131022}, pmid = {36453887}, issn = {2165-0497}, mesh = {Adult ; Humans ; *Gastrointestinal Microbiome/genetics ; RNA, Ribosomal, 16S/genetics ; Cohort Studies ; East Asian People ; *Microbiota ; Feces/microbiology ; }, abstract = {In this study, we aimed to understand the characteristics of the gut microbial composition in a healthy Chinese population and to evaluate if they differed across different regions. In addition, we aimed to understand the changes in the gut microbial composition over time. We collected 239 fecal samples from healthy Chinese adults living in four regions and performed a 1-year time cohort study in a small population in Beijing. The Chinese gut microbiota share 34 core bacterial genera and 39 core bacterial species, which exist in all collected samples. Several disease-related microorganisms (DRMs), virulence factors, and antibiotic resistance genes were found in one or more healthy Chinese samples. Differences in gut microbiota were observed in samples from different regions, locations, individuals, and time points. Compared to other factors, time was associated with a lower degree of change in the gut microbiota. Our findings revealed spatial and temporal changes in the gut microbiota of healthy Chinese individuals. Compared to fecal microbiomes of 152 samples in the publicly released the Human Microbiome Project (HMP) project from the United States, samples in this study have higher variability in the fecal microbiome, with higher richness, Shannon diversity indices, and Pielou evenness indexes, at both the genus and species levels. The microbiota data obtained in this study will provide a detailed basis for further understanding the composition of the gut microbiota in the healthy Chinese population. IMPORTANCE China accounts for approximately 1/5th of the world's total population. Differences in environment, ethnicity, and living habits could impart unique features to the structure of the gut microbiota of Chinese individuals. In 2016, we started to investigate healthy Chinese people and their gut microbiomes. Phase I results for 16S rRNA amplicons have been released. However, owing to the limitations of 16S rRNA amplicon sequencing, the gut microbiome of a healthy Chinese population could not be examined thoroughly at the species level, and the detailed changes in the gut microbiota over time need to be investigated. To address these knowledge gaps, we started a phase II study and investigated the basis for variations in the gut microbiome composition in a healthy Chinese population at the species level using shotgun metagenomics technology. In the phase II study, we also conducted a time scale analysis of fecal samples from healthy Chinese subjects, as a pioneered study, which quantitatively clarified the changes in the gut microbiota at both the spatial and temporal levels and elucidated the distribution pattern of DRMs in healthy Chinese individuals.}, }
@article {pmid36446618, year = {2023}, author = {Li, DD and Zhang, Z and Wang, JN and Zhang, P and Liu, Y and Li, YZ}, title = {Estimate of the degradation potentials of cellulose, xylan, and chitin across global prokaryotic communities.}, journal = {Environmental microbiology}, volume = {25}, number = {2}, pages = {397-409}, doi = {10.1111/1462-2920.16290}, pmid = {36446618}, issn = {1462-2920}, mesh = {*Cellulose/metabolism ; Xylans/metabolism ; Chitin/metabolism ; Polysaccharides/metabolism ; *Chitinases ; }, abstract = {Complex polysaccharides (e.g. cellulose, xylan, and chitin), the most abundant renewable biomass resources available on Earth, are mainly degraded by microorganisms in nature. However, little is known about the global distribution of the enzymes and microorganisms responsible for the degradation of cellulose, xylan, and chitin in natural environments. Through large-scale alignments between the sequences released by the Earth Microbiome Project and sequenced prokaryotic genomes, we determined that almost all prokaryotic communities have the functional potentials to degrade cellulose, xylan, and chitin. The median abundances of genes encoding putative cellulases, xylanases, and chitinases in global prokaryotic communities are 0.51 (0.17-1.01), 0.24 (0.05-0.57), and 0.33 (0.11-0.71) genes/cell, respectively, and the composition and abundance of these enzyme systems are environmentally varied. The taxonomic sources of the three enzymes are highly diverse within prokaryotic communities, and the main factor influencing the diversity is the community's alpha diversity index rather than gene abundance. Moreover, there are obvious differences in taxonomic sources among different communities, and most genera with degradation potentials are narrowly distributed. In conclusion, our analysis preliminarily depicts a panorama of cellulose-, xylan-, and chitin-degrading enzymatic systems across global prokaryotic communities.}, }
@article {pmid36443458, year = {2022}, author = {Shaffer, JP and Nothias, LF and Thompson, LR and Sanders, JG and Salido, RA and Couvillion, SP and Brejnrod, AD and Lejzerowicz, F and Haiminen, N and Huang, S and Lutz, HL and Zhu, Q and Martino, C and Morton, JT and Karthikeyan, S and Nothias-Esposito, M and Dührkop, K and Böcker, S and Kim, HW and Aksenov, AA and Bittremieux, W and Minich, JJ and Marotz, C and Bryant, MM and Sanders, K and Schwartz, T and Humphrey, G and Vásquez-Baeza, Y and Tripathi, A and Parida, L and Carrieri, AP and Beck, KL and Das, P and González, A and McDonald, D and Ladau, J and Karst, SM and Albertsen, M and Ackermann, G and DeReus, J and Thomas, T and Petras, D and Shade, A and Stegen, J and Song, SJ and Metz, TO and Swafford, AD and Dorrestein, PC and Jansson, JK and Gilbert, JA and Knight, R and , }, title = {Standardized multi-omics of Earth's microbiomes reveals microbial and metabolite diversity.}, journal = {Nature microbiology}, volume = {7}, number = {12}, pages = {2128-2150}, pmid = {36443458}, issn = {2058-5276}, support = {R01 DK102932/DK/NIDDK NIH HHS/United States ; R01 GM107550/GM/NIGMS NIH HHS/United States ; K12 GM068524/GM/NIGMS NIH HHS/United States ; U01 AI124316/AI/NIAID NIH HHS/United States ; DP1 AT010885/AT/NCCIH NIH HHS/United States ; U19 AG063744/AG/NIA NIH HHS/United States ; R01 HL140976/HL/NHLBI NIH HHS/United States ; R01 HL134887/HL/NHLBI NIH HHS/United States ; RF1 AG058942/AG/NIA NIH HHS/United States ; }, mesh = {Animals ; *Microbiota/genetics ; Metagenome ; Metagenomics ; Earth, Planet ; Soil ; }, abstract = {Despite advances in sequencing, lack of standardization makes comparisons across studies challenging and hampers insights into the structure and function of microbial communities across multiple habitats on a planetary scale. Here we present a multi-omics analysis of a diverse set of 880 microbial community samples collected for the Earth Microbiome Project. We include amplicon (16S, 18S, ITS) and shotgun metagenomic sequence data, and untargeted metabolomics data (liquid chromatography-tandem mass spectrometry and gas chromatography mass spectrometry). We used standardized protocols and analytical methods to characterize microbial communities, focusing on relationships and co-occurrences of microbially related metabolites and microbial taxa across environments, thus allowing us to explore diversity at extraordinary scale. In addition to a reference database for metagenomic and metabolomic data, we provide a framework for incorporating additional studies, enabling the expansion of existing knowledge in the form of an evolving community resource. We demonstrate the utility of this database by testing the hypothesis that every microbe and metabolite is everywhere but the environment selects. Our results show that metabolite diversity exhibits turnover and nestedness related to both microbial communities and the environment, whereas the relative abundances of microbially related metabolites vary and co-occur with specific microbial consortia in a habitat-specific manner. We additionally show the power of certain chemistry, in particular terpenoids, in distinguishing Earth's environments (for example, terrestrial plant surfaces and soils, freshwater and marine animal stool), as well as that of certain microbes including Conexibacter woesei (terrestrial soils), Haloquadratum walsbyi (marine deposits) and Pantoea dispersa (terrestrial plant detritus). This Resource provides insight into the taxa and metabolites within microbial communities from diverse habitats across Earth, informing both microbial and chemical ecology, and provides a foundation and methods for multi-omics microbiome studies of hosts and the environment.}, }
@article {pmid36423084, year = {2022}, author = {Ganz, HH and Jospin, G and Rojas, CA and Martin, AL and Dahlhausen, K and Kingsbury, DD and Osborne, CX and Entrolezo, Z and Redner, S and Ramirez, B and Eisen, JA and Leahy, M and Keaton, C and Wong, J and Gardy, J and Jarett, JK}, title = {The Kitty Microbiome Project: Defining the Healthy Fecal "Core Microbiome" in Pet Domestic Cats.}, journal = {Veterinary sciences}, volume = {9}, number = {11}, pages = {}, pmid = {36423084}, issn = {2306-7381}, abstract = {Here, we present a taxonomically defined fecal microbiome dataset for healthy domestic cats (Felis catus) fed a range of commercial diets. We used this healthy reference dataset to explore how age, diet, and living environment correlate with fecal microbiome composition. Thirty core bacterial genera were identified. Prevotella, Bacteroides, Collinsella, Blautia, and Megasphaera were the most abundant, and Bacteroides, Blautia, Lachnoclostridium, Sutterella, and Ruminococcus gnavus were the most prevalent. While community composition remained relatively stable across different age classes, the number of core taxa present decreased significantly with age. Fecal microbiome composition varied with host diet type. Cats fed kibble had a slightly, but significantly greater number of core taxa compared to cats not fed any kibble. The core microbiomes of cats fed some raw food contained taxa not as highly prevalent or abundant as cats fed diets that included kibble. Living environment also had a large effect on fecal microbiome composition. Cats living in homes differed significantly from those in shelters and had a greater portion of their microbiomes represented by core taxa. Collectively our work reinforces the findings that age, diet, and living environment are important factors to consider when defining a core microbiome in a population.}, }
@article {pmid36378489, year = {2022}, author = {Gupta, VK and Bakshi, U and Chang, D and Lee, AR and Davis, JM and Chandrasekaran, S and Jin, YS and Freeman, MF and Sung, J}, title = {TaxiBGC: a Taxonomy-Guided Approach for Profiling Experimentally Characterized Microbial Biosynthetic Gene Clusters and Secondary Metabolite Production Potential in Metagenomes.}, journal = {mSystems}, volume = {7}, number = {6}, pages = {e0092522}, pmid = {36378489}, issn = {2379-5077}, support = {R35 GM133475/GM/NIGMS NIH HHS/United States ; }, mesh = {Humans ; Metagenome/genetics ; *Microbiota/genetics ; *Gastrointestinal Microbiome/genetics ; Computational Biology ; Multigene Family/genetics ; }, abstract = {Biosynthetic gene clusters (BGCs) in microbial genomes encode bioactive secondary metabolites (SMs), which can play important roles in microbe-microbe and host-microbe interactions. Given the biological significance of SMs and the current profound interest in the metabolic functions of microbiomes, the unbiased identification of BGCs from high-throughput metagenomic data could offer novel insights into the complex chemical ecology of microbial communities. Currently available tools for predicting BGCs from shotgun metagenomes have several limitations, including the need for computationally demanding read assembly, predicting a narrow breadth of BGC classes, and not providing the SM product. To overcome these limitations, we developed taxonomy-guided identification of biosynthetic gene clusters (TaxiBGC), a command-line tool for predicting experimentally characterized BGCs (and inferring their known SMs) in metagenomes by first pinpointing the microbial species likely to harbor them. We benchmarked TaxiBGC on various simulated metagenomes, showing that our taxonomy-guided approach could predict BGCs with much-improved performance (mean F1 score, 0.56; mean PPV score, 0.80) compared with directly identifying BGCs by mapping sequencing reads onto the BGC genes (mean F1 score, 0.49; mean PPV score, 0.41). Next, by applying TaxiBGC on 2,650 metagenomes from the Human Microbiome Project and various case-control gut microbiome studies, we were able to associate BGCs (and their SMs) with different human body sites and with multiple diseases, including Crohn's disease and liver cirrhosis. In all, TaxiBGC provides an in silico platform to predict experimentally characterized BGCs and their SM production potential in metagenomic data while demonstrating important advantages over existing techniques. IMPORTANCE Currently available bioinformatics tools to identify BGCs from metagenomic sequencing data are limited in their predictive capability or ease of use to even computationally oriented researchers. We present an automated computational pipeline called TaxiBGC, which predicts experimentally characterized BGCs (and infers their known SMs) in shotgun metagenomes by first considering the microbial species source. Through rigorous benchmarking techniques on simulated metagenomes, we show that TaxiBGC provides a significant advantage over existing methods. When demonstrating TaxiBGC on thousands of human microbiome samples, we associate BGCs encoding bacteriocins with different human body sites and diseases, thereby elucidating a possible novel role of this antibiotic class in maintaining the stability of microbial ecosystems throughout the human body. Furthermore, we report for the first time gut microbial BGC associations shared among multiple pathologies. Ultimately, we expect our tool to facilitate future investigations into the chemical ecology of microbial communities across diverse niches and pathologies.}, }
@article {pmid36357382, year = {2022}, author = {Liu, Y and Elworth, RAL and Jochum, MD and Aagaard, KM and Treangen, TJ}, title = {De novo identification of microbial contaminants in low microbial biomass microbiomes with Squeegee.}, journal = {Nature communications}, volume = {13}, number = {1}, pages = {6799}, pmid = {36357382}, issn = {2041-1723}, support = {P01 AI152999/AI/NIAID NIH HHS/United States ; R01 DK128187/DK/NIDDK NIH HHS/United States ; R01 HD091731/HD/NICHD NIH HHS/United States ; T15 LM007093/LM/NLM NIH HHS/United States ; T32 HL098069/HL/NHLBI NIH HHS/United States ; R01 NR014792/NR/NINR NIH HHS/United States ; T32 HD098068/HD/NICHD NIH HHS/United States ; }, mesh = {Humans ; Biomass ; *Microbiota/genetics ; Metagenomics/methods ; Metagenome ; Specimen Handling ; }, abstract = {Computational analysis of host-associated microbiomes has opened the door to numerous discoveries relevant to human health and disease. However, contaminant sequences in metagenomic samples can potentially impact the interpretation of findings reported in microbiome studies, especially in low-biomass environments. Contamination from DNA extraction kits or sampling lab environments leaves taxonomic "bread crumbs" across multiple distinct sample types. Here we describe Squeegee, a de novo contamination detection tool that is based upon this principle, allowing the detection of microbial contaminants when negative controls are unavailable. On the low-biomass samples, we compare Squeegee predictions to experimental negative control data and show that Squeegee accurately recovers putative contaminants. We analyze samples of varying biomass from the Human Microbiome Project and identify likely, previously unreported kit contamination. Collectively, our results highlight that Squeegee can identify microbial contaminants with high precision and thus represents a computational approach for contaminant detection when negative controls are unavailable.}, }
@article {pmid36348188, year = {2022}, author = {Rasmussen, N}, title = {René Dubos, the Autochthonous Flora, and the Discovery of the Microbiome.}, journal = {Journal of the history of biology}, volume = {55}, number = {3}, pages = {537-558}, pmid = {36348188}, issn = {1573-0387}, mesh = {Animals ; Humans ; *Microbiota ; *Anthozoa ; Symbiosis ; }, abstract = {Now characterised by high-throughput sequencing methods that enable the study of microbes without lab culture, the human "microbiome" (the microbial flora of the body) is said to have revolutionary implications for biology and medicine. According to many experts, we must now understand ourselves as "holobionts" like lichen or coral, multispecies superorganisms that consist of animal and symbiotic microbes in combination, because normal physiological function depends on them. Here I explore the 1960s research of biologist René Dubos, a forerunner figure mentioned in some historical accounts of the microbiome, and argue that he arrived at the superorganism concept 40 years before the Human Microbiome Project. This raises the question of why his contribution was not hailed as revolutionary at the time and why Dubos is not remembered for it.}, }
@article {pmid36288838, year = {2022}, author = {Fransson, E and Gudnadottir, U and Hugerth, LW and Itzel, EW and Hamsten, M and Boulund, F and Pennhag, A and Du, J and Schuppe-Koistinen, I and Brusselaers, N and Engstrand, L}, title = {Cohort profile: the Swedish Maternal Microbiome project (SweMaMi) - assessing the dynamic associations between the microbiome and maternal and neonatal adverse events.}, journal = {BMJ open}, volume = {12}, number = {10}, pages = {e065825}, pmid = {36288838}, issn = {2044-6055}, mesh = {Infant ; Pregnancy ; Infant, Newborn ; Female ; Humans ; Child ; Sweden/epidemiology ; *Premature Birth ; Pregnancy Trimester, Third ; Cohort Studies ; *Microbiota ; }, abstract = {PURPOSE: The Swedish Maternal Microbiome (SweMaMi) project was initiated to better understand the dynamics of the microbiome in pregnancy, with longitudinal microbiome sampling, shotgun metagenomics, extensive questionnaires and health registry linkage.<br><br>PARTICIPANTS: Pregnant women were recruited before the 20th gestational week during 2017-2021 in Sweden. In total, 5439 pregnancies (5193 unique women) were included. For 3973 pregnancies (73%), samples were provided at baseline, and for 3141 (58%) at all three timepoints (second and third trimester and postpartum). In total, 38 591 maternal microbiome samples (vaginal, faecal and saliva) and 3109 infant faecal samples were collected. Questionnaires were used to collect information on general, reproductive and mental health, diet and lifestyle, complemented by linkage to the nationwide health registries, also used to follow up the health of the offspring (up to age 10).<br><br>FINDINGS TO DATE: The cohort is fairly representative for the total Swedish pregnant population (data from 2019), with 41% first-time mothers. Women with university level education, born in Sweden, with normal body mass index, not using tobacco-products and aged 30-34 years were slightly over-represented.<br><br>FUTURE PLANS: The sample and data collection were finalised in November 2021. The next steps are the characterisation of the microbial DNA and linkage to the health and demographic information from the questionnaires and registries. The role of the microbiome on maternal and neonatal outcomes and early-childhood diseases will be explored (including preterm birth, miscarriage) and the role and interaction of other risk factors and confounders (including endometriosis, polycystic ovarian syndrome, diet, drug use). This is currently among the largest pregnancy cohorts in the world with longitudinal design and detailed and standardised microbiome sampling enabling follow-up of both mothers and children. The findings are expected to contribute greatly to the field of reproductive health focusing on pregnancy and neonatal outcomes.}, }
@article {pmid36280324, year = {2022}, author = {Gupta, A and Singh, V and Mani, I}, title = {Dysbiosis of human microbiome and infectious diseases.}, journal = {Progress in molecular biology and translational science}, volume = {192}, number = {1}, pages = {33-51}, doi = {10.1016/bs.pmbts.2022.06.016}, pmid = {36280324}, issn = {1878-0814}, mesh = {Humans ; Dysbiosis ; Prebiotics ; *Gastrointestinal Microbiome ; *Microbiota ; *Probiotics ; Bacteria ; *Communicable Diseases ; }, abstract = {Since birth, the human body gets colonized by various communities of symbiotic or commensal microorganisms and they persist till the death of an individual. The human microbiome is comprised of the genomes of microorganisms such as viruses, archaea, eukaryotes, protozoa, and, most remarkably, bacteria. The development of "omics" technologies gave way to the Human Microbiome Project (HMP) which aimed at exploring the collection of microbial genes and genomes inhabiting the human body. Eubiosis, i.e., a healthy and balanced composition of such microbes contributes to the metabolic function, protection against pathogens and provides nutrients and energy to the host. Whereas, an imbalance in the diversity of microorganisms, termed dysbiosis, greatly influences the state of health and disease. This chapter summarizes the impact of gut bacteria on the well-being of humans and highlights the protective role played by the human microbiota during bacterial and viral infections. The condition of dysbiosis and how it plays a role in the establishment of various infections and metabolic disorders such as Clostridioides difficile infection (CFI), inflammatory bowel disease (IBD), cancer, periodontitis, and obesity are described in detail. Further, treatments such as fecal transplantation, probiotics, prebiotics, phage therapy, and CRISPR/Cas system, which target gut microbiota during digestive diseases are also discussed.}, }
@article {pmid36274714, year = {2022}, author = {Zheng, Y and Shi, J and Chen, Q and Deng, C and Yang, F and Wang, Y}, title = {Identifying individual-specific microbial DNA fingerprints from skin microbiomes.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {960043}, pmid = {36274714}, issn = {1664-302X}, abstract = {Skin is an important ecosystem that links the human body and the external environment. Previous studies have shown that the skin microbial community could remain stable, even after long-term exposure to the external environment. In this study, we explore two questions: Do there exist strains or genetic variants in skin microorganisms that are individual-specific, temporally stable, and body site-independent? And if so, whether such microorganismal genetic variants could be used as markers, called "fingerprints" in our study, to identify donors? We proposed a framework to capture individual-specific DNA microbial fingerprints from skin metagenomic sequencing data. The fingerprints are identified on the frequency of 31-mers free from reference genomes and sequence alignments. The 616 metagenomic samples from 17 skin sites at 3-time points from 12 healthy individuals from Integrative Human Microbiome Project were adopted. Ultimately, one contig for each individual is assembled as a fingerprint. And results showed that 89.78% of the skin samples despite body sites could identify their donors correctly. It is observed that 10 out of 12 individual-specific fingerprints could be aligned to Cutibacterium acnes. Our study proves that the identified fingerprints are temporally stable, body site-independent, and individual-specific, and can identify their donors with enough accuracy. The source code of the genetic identification framework is freely available at https://github.com/Ying-Lab/skin_fingerprint.}, }
@article {pmid36268225, year = {2022}, author = {Khorsand, B and Asadzadeh Aghdaei, H and Nazemalhosseini-Mojarad, E and Nadalian, B and Nadalian, B and Houri, H}, title = {Overrepresentation of Enterobacteriaceae and Escherichia coli is the major gut microbiome signature in Crohn's disease and ulcerative colitis; a comprehensive metagenomic analysis of IBDMDB datasets.}, journal = {Frontiers in cellular and infection microbiology}, volume = {12}, number = {}, pages = {1015890}, pmid = {36268225}, issn = {2235-2988}, mesh = {Humans ; *Colitis, Ulcerative ; *Crohn Disease/microbiology ; *Gastrointestinal Microbiome/genetics ; Metagenome ; Escherichia coli ; Siderophores ; Lipopolysaccharides ; *Inflammatory Bowel Diseases/microbiology ; Feces/microbiology ; *Escherichia coli Infections ; Sulfur ; Nitrogen ; }, abstract = {OBJECTIVES: A number of converging strands of research suggest that the intestinal Enterobacteriaceae plays a crucial role in the development and progression of inflammatory bowel disease (IBD), however, the changes in the abundance of Enterobacteriaceae species and their related metabolic pathways in Crohn's disease (CD) and ulcerative colitis (UC) compared to healthy people are not fully explained by comprehensive comparative metagenomics analysis. In the current study, we investigated the alternations of the Enterobacterales population in the gut microbiome of patients with CD and UC compared to healthy subjects.<br><br>METHODS: Metagenomic datasets were selected from the Integrative Human Microbiome Project (HMP2) through the Inflammatory Bowel Disease Multi'omics Database (IBDMDB). We performed metagenome-wide association studies on fecal samples from 191 CD patients, 132 UC patients, and 125 healthy controls (HCs). We used the metagenomics dataset to study bacterial community structure, relative abundance, differentially abundant bacteria, functional analysis, and Enterobacteriaceae-related biosynthetic pathways.<br><br>RESULTS: Compared to the gut microbiome of HCs, six Enterobacteriaceae species were significantly elevated in both CD and UC patients, including Escherichia coli, Klebsiella variicola, Klebsiella quasipneumoniae, Klebsiella pneumoniae, Proteus mirabilis, Citrobacter freundii, and Citrobacter youngae, while Klebsiella oxytoca, Morganella morganii, and Citrobacter amalonaticus were uniquely differentially abundant and enriched in the CD cohort. Four species were uniquely differentially abundant and enriched in the UC cohort, including Citrobacter portucalensis, Citrobacter pasteurii, Citrobacter werkmanii, and Proteus hauseri. Our analysis also showed a dramatically increased abundance of E. coli in their intestinal bacterial community. Biosynthetic pathways of aerobactin siderophore, LPS, enterobacterial common antigen, nitrogen metabolism, and sulfur relay systems encoded by E. coli were significantly elevated in the CD samples compared to the HCs. Menaquinol biosynthetic pathways were associated with UC that belonged to K. pneumoniae strains.<br><br>CONCLUSIONS: In conclusion, compared with healthy people, the taxonomic and functional composition of intestinal bacteria in CD and UC patients was significantly shifted to Enterobacteriaceae species, mainly E. coli and Klebsiella species.}, }
@article {pmid36258167, year = {2022}, author = {Vikramdeo, KS and Anand, S and Pierce, JY and Singh, AP and Singh, S and Dasgupta, S}, title = {Distribution of microbiota in cervical preneoplasia of racially disparate populations.}, journal = {BMC cancer}, volume = {22}, number = {1}, pages = {1074}, pmid = {36258167}, issn = {1471-2407}, support = {R01 CA224306/CA/NCI NIH HHS/United States ; R01 CA231925/CA/NCI NIH HHS/United States ; CA231925, CA224306/NH/NIH HHS/United States ; }, mesh = {Female ; Humans ; Papillomaviridae/genetics ; RNA, Ribosomal, 16S/genetics ; *Papillomavirus Infections/complications ; Dysbiosis ; *Uterine Cervical Neoplasms/pathology ; *Microbiota/genetics ; *Uterine Cervical Dysplasia/epidemiology ; }, abstract = {BACKGROUNDS: Microbiome dysbiosis is an important contributing factor in tumor development and thus may be a risk predictor for human malignancies. In the United States, women with Hispanic/Latina (HIS) and African American (AA) background have a higher incidence of cervical cancer and poorer outcomes than Caucasian American (CA) women.<br><br>METHODS: Here, we assessed the distribution pattern of microbiota in cervical intraepithelial neoplasia (CIN) lesions obtained from HIS (n&#x2009;=&#x2009;12), AA (n&#x2009;=&#x2009;12), and CA (n&#x2009;=&#x2009;12) women, who were screened for CC risk assessment. We employed a 16S rRNA gene sequencing approach adapted from the NIH-Human Microbiome Project to identify the microbial niche in all CIN lesions (n&#x2009;=&#x2009;36).<br><br>RESULTS: We detected an appreciably decreased abundance of beneficial Lactobacillus in the CIN lesions of the AA and HIS women compared to the CA women. Differential abundance of potentially pathogenic Prevotella, Delftia, Gardnerella, and Fastidiosipila was also evident among the various racial groups. An increased abundance of Micrococcus was also evident in AA and HIS women compared to the CA women. The detection level of Rhizobium was higher among the AA ad CA women compared to the HIS women. In addition to the top 10 microbes, a unique niche of 27 microbes was identified exclusively in women with a histopathological diagnosis of CIN. Among these microbes, a group of 8 microbiota; Rubellimicrobium, Podobacter, Brevibacterium, Paracoccus, Atopobium, Brevundimonous, Comamonous, and Novospingobium was detected only in the CIN lesions obtained from AA and CA women.<br><br>CONCLUSIONS: Microbial dysbiosis in the cervical epithelium represented by an increased ratio of potentially pathogenic to beneficial microbes may be associated with increased CC risk disparities. Developing a race-specific reliable panel of microbial markers could be beneficial for CC risk assessment, disease prevention, and/or therapeutic guidance.}, }
@article {pmid36233254, year = {2022}, author = {Rinaldi, F and Pinto, D and Borsani, E and Castrezzati, S and Amedei, A and Rezzani, R}, title = {The First Evidence of Bacterial Foci in the Hair Part and Dermal Papilla of Scalp Hair Follicles: A Pilot Comparative Study in Alopecia Areata.}, journal = {International journal of molecular sciences}, volume = {23}, number = {19}, pages = {}, pmid = {36233254}, issn = {1422-0067}, support = {private//Giuliani SpA/ ; }, mesh = {Adult ; *Alopecia Areata ; Hair Follicle/pathology ; Humans ; *Microbiota ; Middle Aged ; Scalp/pathology ; Young Adult ; }, abstract = {The role of the microbiome in hair follicle (HF) growth represents a growing field of research. Here, we studied the bacterial population in the scalp hair follicles of subjects with alopecia areata (AA). Two Healthy and two AA subjects, respectively (20−60 years old), were enrolled and studied regarding the microbial community in the subepidermal scalp compartments by means of a 4-mm biopsy punch. Samples were examined by 16S sequencing, histochemical staining (Gram’s method), and transmission electron microscopy (TEM). Bacterial foci were observed in the AA subjects’ follicles with both the two adopted complementary approaches (electron microscopy and Gram staining). Significant (p < 0.05) differences were also found in the three-layer biopsy samples (p < 0.05) regarding the bacterial population. In particular, in the deep epidermis and dermis levels, a significant (p < 0.05) lower abundance of Firmicutes and a higher abundance of Proteobacteria were found in AA samples compared to the healthy control. Firmicutes also showed a significant (p < 0.05) lower abundance in hypodermis in AA subjects. In addition, Enterobacteriaceae and the genera Streptococcus, Gemella, Porphyromonas, and Granulicatella were relatively more abundant in AA groups at the deep epidermis level. The Staphylococcus and Flavobacterium genera were significantly less abundant in AA samples than in controls in all three-layer biopsy samples (p < 0.05). In contrast, Veillonella and Neisseriaceae were relatively more abundant in the healthy control group compared to the AA sample. Therefore, higher alpha diversity was observed in all three-layer biopsy samples of AA patients compared to the control. In conclusion, our data suggest that tAA could be defined as a “hair disease associated with dysregulated microbiome-immunity axis of hair follicles”.}, }
@article {pmid36231000, year = {2022}, author = {Prakash, A and Nourianpour, M and Senok, A and Atiomo, W}, title = {Polycystic Ovary Syndrome and Endometrial Cancer: A Scoping Review of the Literature on Gut Microbiota.}, journal = {Cells}, volume = {11}, number = {19}, pages = {}, pmid = {36231000}, issn = {2073-4409}, mesh = {Dysbiosis/complications/microbiology ; *Endometrial Neoplasms ; Female ; *Gastrointestinal Microbiome/physiology ; Humans ; *Microbiota ; *Polycystic Ovary Syndrome ; }, abstract = {Gut dysbiosis has been associated with polycystic ovary syndrome (PCOS) and endometrial cancer (EC) but no studies have investigated whether gut dysbiosis may explain the increased endometrial cancer risk in polycystic ovary syndrome. The aim of this scoping review is to evaluate the extent and nature of published studies on the gut microbiota in polycystic ovary syndrome and endometrial cancer and attempt to find any similarities between the composition of the microbiota. We searched for publications ranging from the years 2016 to 2022, due to the completion date of the 'Human Microbiome Project' in 2016. We obtained 200 articles by inputting keywords such as 'gut microbiome', 'gut microbiota', 'gut dysbiosis', 'PCOS', and 'endometrial cancer' into search engines such as PubMed and Scopus. Of the 200 identified in our initial search, we included 25 articles in our final review after applying the exclusion and inclusion criteria. Although the literature is growing in this field, we did not identify enough published studies to investigate whether gut dysbiosis may explain the increased EC risk in PCOS. Within the studies identified, we were unable to identify any consistent patterns of the microbiome similarly present in studies on women with PCOS compared with women with EC. Although we found that the phylum Firmicutes was similarly decreased in women with PCOS and studies on women with EC, there was however significant variability within the studies identified making it highly likely that this may have arisen by chance. Further research pertaining to molecular and microbiological mechanisms in relation to the gut microbiome is needed to elucidate a greater understanding of its contribution to the pathophysiology of endometrial cancer in patients with polycystic ovarian syndrome.}, }
@article {pmid36160151, year = {2022}, author = {Aboul Naga, SH and Hassan, LM and El Zanaty, RT and Refaat, M and Amin, RH and Ragab, G and Soliman, MM}, title = {Behçet uveitis: Current practice and future perspectives.}, journal = {Frontiers in medicine}, volume = {9}, number = {}, pages = {968345}, pmid = {36160151}, issn = {2296-858X}, abstract = {Described as early as Hippocrates in his "Third Book of Endemic Diseases," Behçet's Disease (BD), also known as "The Silk Road Disease" following its initial demographics, consists of a triad of recurrent oro-genital ulcers and associated uveitis. Current demographics and rising percentages of patients seen far beyond the Silk Road in Ocular Inflammatory Disease and Uveitis Clinics list BD uveitis as one of the frontliners of non-infectious autoinflammatory eye diseases. Clinical features of BD and juvenile-onset BD are detailed alongside various approaches in classification and suggested algorithms for diagnosis that are outlined in this review. With the ongoing Human Microbiome Project and studies such as the MAMBA study, the role of the human microbiome in BD is highlighted in the pathophysiology of BD to include the current research and literature perspective. Furthermore, with the advancement of recent diagnostic and investigative techniques, especially in the field of Optical Coherence Tomography (OCT), disease-related characteristics are updated to encompass SD, EDI and OCT-angiography characteristics of BD. Having entered the era of biologic therapy, the role of various specific cytokine-blocking biologic drugs, such as TNF-α inhibitors (e.g., adalimumab, infliximab), interferon α-2a inhibitors, IL-6 and IL-1 inhibitors are presented and contrasted alongside the conventional immunosuppressant drugs and the classic old gold standard: corticosteroids (systemic or local). Finally, with the ongoing SARS-CoV-2 pandemic, it was not possible to conclude the review without reviewing the latest evidence-based literature reporting BD morbidity in this era, the observed pattern and treatment recommendations as well as those related to reported post-vaccine complications and emergence of BD.}, }
@article {pmid36083529, year = {2022}, author = {de Lima Ferreira, JK and de Mello Varani, A and Tótola, MR and Fernandes Almeida, M and de Sousa Melo, D and Ferreira Silva E Batista, C and Chalfun-Junior, A and Pimenta de Oliveira, KK and Wurdig Roesch, LF and Satler Pylro, V}, title = {Phylogenomic characterization and pangenomic insights into the surfactin-producing bacteria Bacillus subtilis strain RI4914.}, journal = {Brazilian journal of microbiology : [publication of the Brazilian Society for Microbiology]}, volume = {53}, number = {4}, pages = {2051-2063}, pmid = {36083529}, issn = {1678-4405}, support = {404651/2018-6//Conselho Nacional de Desenvolvimento Cient&#xed;fico e Tecnol&#xf3;gico/ ; 303061/2019-7//Conselho Nacional de Desenvolvimento Cient&#xed;fico e Tecnol&#xf3;gico/ ; 133550/2019-2//Conselho Nacional de Desenvolvimento Cient&#xed;fico e Tecnol&#xf3;gico/ ; Finance Code 001//Coordena&#xe7;&#xe3;o de Aperfei&#xe7;oamento de Pessoal de N&#xed;vel Superior/ ; 001//Brazilian Microbiome Project/ ; }, mesh = {*Bacillus subtilis/genetics/metabolism ; Phylogeny ; *Peptides, Cyclic/genetics/metabolism ; Lipopeptides ; Operon ; Bacterial Proteins/metabolism ; }, abstract = {Bacillus subtilis is a versatile bacterial species able to produce surfactin, a lipopeptide biosurfactant. We carried out the phylogenomic characterization and pangenomic analyses using available B. subtilis complete genomes. Also, we report the whole genome of the biosurfactant-producing B. subtilis strain RI4914 that was isolated from effluent water from an oil exploration field. We applied a hybrid sequencing approach using both long- and short-read sequencing technologies to generate a highly accurate, single-chromosome genome. The pangenomics analysis of 153 complete genomes classified as B. subtilis retrieved from the NCBI shows an open pangenome composed of 28,511 accessory genes, which agrees with the high genetic plasticity of the species. Also, this analysis suggests that surfactin production is a common trait shared by members of this species since the srfA operon is highly conserved among the B. subtilis strains found in most of the assemblies available. Finally, increased surfactin production corroborates the higher srfAA gene expression in B. subtilis strain RI4914.}, }
@article {pmid36047699, year = {2022}, author = {An, U and Shenhav, L and Olson, CA and Hsiao, EY and Halperin, E and Sankararaman, S}, title = {STENSL: Microbial Source Tracking with ENvironment SeLection.}, journal = {mSystems}, volume = {7}, number = {5}, pages = {e0099521}, pmid = {36047699}, issn = {2379-5077}, support = {R35 GM125055/GM/NIGMS NIH HHS/United States ; R01 HG011345/HG/NHGRI NIH HHS/United States ; }, mesh = {*Microbiota ; Algorithms ; Machine Learning ; }, abstract = {Microbial source tracking analysis has emerged as a widespread technique for characterizing the properties of complex microbial communities. However, this analysis is currently limited to source environments sampled in a specific study. In order to expand the scope beyond one single study and allow the exploration of source environments using large databases and repositories, such as the Earth Microbiome Project, a source selection procedure is required. Such a procedure will allow differentiating between contributing environments and nuisance ones when the number of potential sources considered is high. Here, we introduce STENSL (microbial Source Tracking with ENvironment SeLection), a machine learning method that extends common microbial source tracking analysis by performing an unsupervised source selection and enabling sparse identification of latent source environments. By incorporating sparsity into the estimation of potential source environments, STENSL improves the accuracy of true source contribution, while significantly reducing the noise introduced by noncontributing ones. We therefore anticipate that source selection will augment microbial source tracking analyses, enabling exploration of multiple source environments from publicly available repositories while maintaining high accuracy of the statistical inference. IMPORTANCE Microbial source tracking is a powerful tool to characterize the properties of complex microbial communities. However, this analysis is currently limited to source environments sampled in a specific study. In many applications there is a clear need to consider source selection over a large array of microbial environments, external to the study. To this end, we developed STENSL (microbial Source Tracking with ENvironment SeLection), an expectation-maximization algorithm with sparsity that enables the identification of contributing sources among a large set of potential microbial environments. With the unprecedented expansion of microbiome data repositories such as the Earth Microbiome Project, recording over 200,000 samples from more than 50 types of categorized environments, STENSL takes the first steps in performing automated source exploration and selection. STENSL is significantly more accurate in identifying the contributing sources as well as the unknown source, even when considering hundreds of potential source environments, settings in which state-of-the-art microbial source tracking methods add considerable error.}, }
@article {pmid35993401, year = {2022}, author = {Wiesmann, C and Lehr, K and Kupcinskas, J and Vilchez-Vargas, R and Link, A}, title = {Primers matter: Influence of the primer selection on human fungal detection using high throughput sequencing.}, journal = {Gut microbes}, volume = {14}, number = {1}, pages = {2110638}, pmid = {35993401}, issn = {1949-0984}, mesh = {DNA, Fungal ; Fungi/genetics ; *Gastrointestinal Microbiome/genetics ; High-Throughput Nucleotide Sequencing/methods ; Humans ; *Mycobiome/genetics ; }, abstract = {Microbiota research has received an increasing attention for its role in disease development and fungi are considered as one of the key players in the microbial niche. Various sequencing approaches have been applied to uncover the role of fungal community in health and disease; however, little is known on the performance of various primers and comparability between the studies. Motivated by the recent publications, we performed a systematic comparison of the 18S and ITS regions to identify the impact of various primers on the sequencing results. Using four pairs of primers extensively used in literature, fungal community was retrieve from 25 fecal samples, and applying high throughput sequencing; and the results were compared in order to select the most suitable primers for fungal detection in human fecal samples. Considering the high variability between samples, primers described in the Earth microbiome project detected the broadest fungal spectrum suggesting its superior performance in mycobiome research.}, }
@article {pmid35973395, year = {2022}, author = {Scricciolo, A and Lombardo, V and Elli, L and Bascuñán, KA and Doneda, L and Rinaldi, F and Pinto, D and Araya, M and Costantino, A and Vecchi, M and Roncoroni, L}, title = {Use of a proline-specific endopeptidase to reintroduce gluten in patients with non-coeliac gluten sensitivity: A randomized trial.}, journal = {Clinical nutrition (Edinburgh, Scotland)}, volume = {41}, number = {9}, pages = {2025-2030}, doi = {10.1016/j.clnu.2022.07.029}, pmid = {35973395}, issn = {1532-1983}, mesh = {Adult ; *Celiac Disease ; Diet, Gluten-Free ; *Glutens/adverse effects ; Humans ; Proline ; Prolyl Oligopeptidases ; Quality of Life ; }, abstract = {BACKGROUND: A gluten-free diet (GFD) is the main therapy for non-coeliac gluten sensitivity (NCGS). However, the availability of novel enzymes with the ability to digest gluten could represent a therapeutic opportunity for NCGS patients to avoid a GFD.<br><br>AIMS: To evaluate the controlled reintroduction of gluten with or without the endopeptidase P1016 in NCGS patients.<br><br>METHODS: This is a randomized, double-blind, placebo-controlled monocentric study, Registered under ClinicalTrials.gov Identifier no. NCT01864993. Gluten was reintroduced incrementally over a 3-week period under nutritional control. NCGS patients were randomized into two groups and administered P1016 or placebo during gluten reintroduction. We evaluated symptoms (visual analogue scale, VAS), quality of life (SF-36) and mental health symptoms (SCL-90) on a weekly basis.<br><br>RESULTS: We enrolled a total 23 patients who were allocated to a placebo group (n&#xa0;=&#xa0;11, age 38.4&#xa0;&#xb1;&#xa0;2.9) or an intervention group (n&#xa0;=&#xa0;12, age 39.5&#xa0;&#xb1;&#xa0;3.1). No effect of P1016 on symptoms was found. During gluten reintroduction, patients reported a significant increase in abdominal pain and a worsening of stool consistency. Furthermore, no differences were found between the groups regarding SCL-90 and SF-36 scores.<br><br>CONCLUSIONS: Our results demonstrate a lack of effect of P1016 in the management of NCGS patients and the possible reintroduction of gluten.}, }
@article {pmid35966676, year = {2022}, author = {Wei, Q and Li, Z and Gu, Z and Liu, X and Krutmann, J and Wang, J and Xia, J}, title = {Shotgun metagenomic sequencing reveals skin microbial variability from different facial sites.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {933189}, pmid = {35966676}, issn = {1664-302X}, abstract = {Biogeography (body site) is known to be one of the main factors influencing the composition of the skin microbial community. However, site-associated microbial variability at a fine-scale level was not well-characterized since there was a lack of high-resolution recognition of facial microbiota across kingdoms by shotgun metagenomic sequencing. To investigate the explicit microbial variance in the human face, 822 shotgun metagenomic sequencing data from Han Chinese recently published by our group, in combination with 97 North American samples from NIH Human Microbiome Project (HMP), were reassessed. Metagenomic profiling of bacteria, fungi, and bacteriophages, as well as enriched function modules from three facial sites (forehead, cheek, and the back of the nose), was analyzed. The results revealed that skin microbial features were more alike in the forehead and cheek while varied from the back of the nose in terms of taxonomy and functionality. Analysis based on biogeographic theories suggested that neutral drift with niche selection from the host could possibly give rise to the variations. Of note, the abundance of porphyrin-producing species, i.e., Cutibacterium acnes, Cutibacterium avidum, Cutibacterium granulosum, and Cutibacterium namnetense, was all the highest in the back of the nose compared with the forehead/cheek, which was consistent with the highest porphyrin level on the nose in our population. Sequentially, the site-associated microbiome variance was confirmed in American populations; however, it was not entirely consistent. Furthermore, our data revealed correlation patterns between Propionibacterium acnes bacteriophages with genus Cutibacterium at different facial sites in both populations; however, C. acnes exhibited a distinct correlation with P. acnes bacteriophages in Americans/Chinese. Taken together, in this study, we explored the fine-scale facial site-associated changes in the skin microbiome and provided insight into the ecological processes underlying facial microbial variations.}, }
@article {pmid35913193, year = {2022}, author = {Zheng, X and Dai, X and Zhu, Y and Yang, J and Jiang, H and Dong, H and Huang, L}, title = {(Meta)Genomic Analysis Reveals Diverse Energy Conservation Strategies Employed by Globally Distributed Gemmatimonadota.}, journal = {mSystems}, volume = {7}, number = {4}, pages = {e0022822}, pmid = {35913193}, issn = {2379-5077}, mesh = {Phylogeny ; RNA, Ribosomal, 16S/genetics ; *Bacteria ; Genomics ; *Microbiota/genetics ; }, abstract = {Gemmatimonadota is a phylum-level lineage distributed widely but rarely reported. Only six representatives of Gemmatimonadota have so far been isolated and cultured in laboratory. The physiology, ecology, and evolutionary history of this phylum remain unknown. The 16S rRNA gene survey of our salt lake and deep-sea sediments, and Earth Microbiome Project (EMP) samples, reveals that Gemmatimonadota exist in diverse environments globally. In this study, we retrieved 17 metagenome-assembled genomes (MAGs) from salt lake sediments (12 MAGs) and deep-sea sediments (5 MAGs). Analysis of these MAGs and the nonredundant MAGs or genomes from public databases reveals Gemmatimonadota can degrade various complex organic substrates, and mainly employ heterotrophic pathways (e.g., glycolysis and tricarboxylic acid [TCA] cycle) for growth via aerobic respiration. And the processes of sufficient energy being stored in glucose through gluconeogenesis, followed by the synthesis of more complex compounds, are prevalent in Gemmatimonadota. A highly expandable pangenome for Gemmatimonadota has been observed, which presumably results from their adaptation to thriving in diverse environments. The enrichment of the Na[+]/H[+] antiporter in the SG8-23 order represents their adaptation to salty habitats. Notably, we identified a novel lineage of the SG8-23 order, which is potentially anoxygenic phototrophic. This lineage is not closely related to the phototrophs in the order of Gemmatimonadales. The two orders differ distinctly in the gene organization and phylogenetic relationship of their photosynthesis gene clusters, indicating photosystems in Gemmatimonadota have evolved in two independent routes. IMPORTANCE The phylum Gemmatimonadota is widely distributed in various environments. However, their physiology, ecology and evolutionary history remain unknown, primary due to the limited cultured isolates and available genomes. We were intrigued to find out how widespread this phylum is, and how it can thrive under diverse conditions. Our results here expand the knowledge of the genetic and metabolic diversity of Gemmatimonadota, and shed light on the diverse energy conservation strategies (i.e., oxidative phosphorylation, substrate phosphorylation, and photosynthetic phosphorylation) responsible for their global distribution. Moreover, gene organization and phylogenetic analysis of photosynthesis gene clusters in Gemmatimonadota provide a valuable insight into the evolutionary history of photosynthesis.}, }
@article {pmid35879415, year = {2022}, author = {Lopera-Maya, EA and Kurilshikov, A and van der Graaf, A and Hu, S and Andreu-Sánchez, S and Chen, L and Vila, AV and Gacesa, R and Sinha, T and Collij, V and Klaassen, MAY and Bolte, LA and Gois, MFB and Neerincx, PBT and Swertz, MA and ,  and Harmsen, HJM and Wijmenga, C and Fu, J and Weersma, RK and Zhernakova, A and Sanna, S}, title = {Author Correction: Effect of host genetics on the gut microbiome in 7,738 participants of the Dutch Microbiome Project.}, journal = {Nature genetics}, volume = {54}, number = {9}, pages = {1448}, doi = {10.1038/s41588-022-01164-2}, pmid = {35879415}, issn = {1546-1718}, }
@article {pmid35877716, year = {2022}, author = {Silva, SG and Paula, P and da Silva, JP and Mil-Homens, D and Teixeira, MC and Fialho, AM and Costa, R and Keller-Costa, T}, title = {Insights into the Antimicrobial Activities and Metabolomes of Aquimarina (Flavobacteriaceae, Bacteroidetes) Species from the Rare Marine Biosphere.}, journal = {Marine drugs}, volume = {20}, number = {7}, pages = {}, pmid = {35877716}, issn = {1660-3397}, support = {Fundo Azul program - FA_05_2017_032//Dire&#xe7;&#xe3;o-Geral de Pol&#xed;tica do Mar/ ; EMBRC.PT ALG-01-0145-FEDER-022121//CRESC Algarve 2020 and COMPETE 2020/ ; PTDC/MAR-BIO/1547/2014, UIDB/04565/2020, UIDP/04565/2020, LA/P/0140/2020, UIDB/04326/2020, PD/BD/143029/2018//Funda&#xe7;&#xe3;o para a Ci&#xea;ncia e Tecnologia/ ; 22231/01/SAICT/2016//Lisboa2020/ ; }, mesh = {*Anti-Infective Agents/metabolism/pharmacology ; Bacteroidetes/genetics ; *Biological Products/metabolism/pharmacology ; Ecosystem ; *Flavobacteriaceae/genetics ; Humans ; Metabolome ; *Methicillin-Resistant Staphylococcus aureus ; Phylogeny ; }, abstract = {Two novel natural products, the polyketide cuniculene and the peptide antibiotic aquimarin, were recently discovered from the marine bacterial genus Aquimarina. However, the diversity of the secondary metabolite biosynthetic gene clusters (SM-BGCs) in Aquimarina genomes indicates a far greater biosynthetic potential. In this study, nine representative Aquimarina strains were tested for antimicrobial activity against diverse human-pathogenic and marine microorganisms and subjected to metabolomic and genomic profiling. We found an inhibitory activity of most Aquimarina strains against Candida glabrata and marine Vibrio and Alphaproteobacteria species. Aquimarina sp. Aq135 and Aquimarina muelleri crude extracts showed particularly promising antimicrobial activities, amongst others against methicillin-resistant Staphylococcus aureus. The metabolomic and functional genomic profiles of Aquimarina spp. followed similar patterns and were shaped by phylogeny. SM-BGC and metabolomics networks suggest the presence of novel polyketides and peptides, including cyclic depsipeptide-related compounds. Moreover, exploration of the ‘Sponge Microbiome Project’ dataset revealed that Aquimarina spp. possess low-abundance distributions worldwide across multiple marine biotopes. Our study emphasizes the relevance of this member of the microbial rare biosphere as a promising source of novel natural products. We predict that future metabologenomics studies of Aquimarina species will expand the spectrum of known secondary metabolites and bioactivities from marine ecosystems.}, }
@article {pmid35854695, year = {2022}, author = {Therdtatha, P and Shinoda, A and Nakayama, J}, title = {Crisis of the Asian gut: associations among diet, microbiota, and metabolic diseases.}, journal = {Bioscience of microbiota, food and health}, volume = {41}, number = {3}, pages = {83-93}, pmid = {35854695}, issn = {2186-6953}, abstract = {The increase of lifestyle-related diseases in Asia has recently become remarkably serious. This has been associated with a change in dietary habits that may alter the complex gut microbiota and its metabolic function in Asian people. Notably, the penetration of modern Western diets into Asia, which has been accompanied by an increase in fat content and decrease in plant-derived dietary fiber, is restructuring the Asian gut microbiome. In this review, we introduce the current status of obesity and diabetes in Asia and discuss the links of changes in dietary style with gut microbiota alterations which may predispose Asian people to metabolic diseases.}, }
@article {pmid35849580, year = {2022}, author = {Pinto, D and Calabrese, FM and De Angelis, M and Celano, G and Giuliani, G and Rinaldi, F}, title = {Lichen Planopilaris: The first biopsy layer microbiota inspection.}, journal = {PloS one}, volume = {17}, number = {7}, pages = {e0269933}, pmid = {35849580}, issn = {1932-6203}, mesh = {Alopecia/metabolism ; Biopsy ; Humans ; Inflammation ; Interleukin-23/genetics ; *Lichen Planus/pathology ; *Microbiota/genetics ; RNA, Ribosomal, 16S/genetics ; }, abstract = {Lichen Planopilaris (LPP) is a lymphatic disease affecting the scalp that is characterized by a chronic and destructive inflammation process, named as 'cicatricial alopecia' in which the hair follicles are targeted and may involve predominantly lymphocytes or neutrophils. Scalp and biopsy layers have never been used to investigate microbial community composition and its relative taxa abundances in LPP. We sought to examine the significant taxa of this chronic relapsing inflammatory skin disease, together with inspect the existing connections with metabolic pathways featuring this microbial community. We used a multilevel analysis based on 16S rRNA marker sequencing in order to detect OTU abundances in pathologic/healthy samples, real time PCR for measuring the levels of IL-23 interleukin expression and urinary metabolomics to find out volatile organic metabolites (VOMs). By using a linear regression model, we described peculiar taxa that significantly differentiated LPP and healthy samples. We inspected taxa abundances and interleukin mRNA levels and the Microbacteriaceae family resulted negatively correlated with the IL-23 expression. Moreover, starting from 16S taxa abundances, we predicted the metabolic pathways featuring this microbial community. By inspecting microbial composition, sample richness, metabolomics profiles and the relative metabolic pathways in a cohort of LPP and healthy samples we deepened the contribution of significant taxa that are connected to inflammation maintenance and microbiota plasticity in LPP pathology.}, }
@article {pmid35832621, year = {2022}, author = {Balaji, A and Sapoval, N and Seto, C and Leo Elworth, RA and Fu, Y and Nute, MG and Savidge, T and Segarra, S and Treangen, TJ}, title = {KOMB: K-core based de novo characterization of copy number variation in microbiomes.}, journal = {Computational and structural biotechnology journal}, volume = {20}, number = {}, pages = {3208-3222}, pmid = {35832621}, issn = {2001-0370}, support = {U01 AI124290/AI/NIAID NIH HHS/United States ; }, abstract = {Characterizing metagenomes via kmer-based, database-dependent taxonomic classification has yielded key insights into underlying microbiome dynamics. However, novel approaches are needed to track community dynamics and genomic flux within metagenomes, particularly in response to perturbations. We describe KOMB, a novel method for tracking genome level dynamics within microbiomes. KOMB utilizes K-core decomposition to identify Structural variations (SVs), specifically, population-level Copy Number Variation (CNV) within microbiomes. K-core decomposition partitions the graph into shells containing nodes of induced degree at least K, yielding reduced computational complexity compared to prior approaches. Through validation on a synthetic community, we show that KOMB recovers and profiles repetitive genomic regions in the sample. KOMB is shown to identify functionally-important regions in Human Microbiome Project datasets, and was used to analyze longitudinal data and identify keystone taxa in Fecal Microbiota Transplantation (FMT) samples. In summary, KOMB represents a novel graph-based, taxonomy-oblivious, and reference-free approach for tracking CNV within microbiomes. KOMB is open source and available for download at https://gitlab.com/treangenlab/komb.}, }
@article {pmid35816586, year = {2023}, author = {Reis, DJ and Kaizer, AM and Kinney, AR and Bahraini, NH and Forster, JE and Brenner, LA}, title = {The unique association of posttraumatic stress disorder with hypertension among veterans: A replication of Kibler et al. (2009) using Bayesian estimation and data from the United States-Veteran Microbiome Project.}, journal = {Psychological trauma : theory, research, practice and policy}, volume = {15}, number = {1}, pages = {131-139}, pmid = {35816586}, issn = {1942-969X}, support = {//National Institutes of Health; National Heart, Lung, and Blood Institute/ ; //State of Colorado/ ; K01 HL151754/HL/NHLBI NIH HHS/United States ; //US Department of Defense/ ; //Rocky Mountain Mental Illness Research, Education, and Clinical Center/ ; /NH/NIH HHS/United States ; //US Department of Veterans Affairs/ ; //US Department of Veterans Affairs; Office of Academic Affiliations; Advanced Fellowship Program in Mental Illness Research and Treatment/ ; }, mesh = {Humans ; United States/epidemiology ; *Stress Disorders, Post-Traumatic/psychology ; *Veterans/psychology ; Bayes Theorem ; *Depressive Disorder, Major/epidemiology ; Comorbidity ; *Hypertension/epidemiology ; }, abstract = {OBJECTIVE: Kibler et al. (2009) reported that hypertension was related to PTSD independent of depression. These two conditions have significant diagnostic overlap. The present study sought to conceptually replicate this work with a veteran sample, using Bayesian estimation to directly update past results, as well as examine symptom severity scores in relation to hypertension.<br><br>METHOD: This was a secondary analysis of data obtained from the United States-Veteran Microbiome Project. Lifetime diagnoses of PTSD and major depressive disorder (MDD) were obtained from a structured clinical interview and hypertension diagnoses were extracted from electronic medical records. PTSD and depressive symptom severity were obtained from self-report measures. Logistic regressions with Bayesian estimation were used to estimate the associations between hypertension and (a) psychiatric diagnostic history and (b) symptom severity scores.<br><br>RESULTS: Compared with veterans without lifetime diagnoses of either disorder, the PTSD-only group was estimated to have a 29% increase in hypertension risk, and the PTSD + MDD group was estimated to have a 66% increase in hypertension risk. Additionally, higher levels of PTSD symptom severity were associated with a higher risk of hypertension.<br><br>CONCLUSION: PTSD diagnosis and symptom severity are uniquely associated with hypertension, independent of MDD or depressive symptom severity. These results support previous findings that PTSD might be a modifiable risk factor for the prevention and treatment of hypertension. (PsycInfo Database Record (c) 2023 APA, all rights reserved).}, }
@article {pmid35788347, year = {2022}, author = {Nagata, N and Nishijima, S and Miyoshi-Akiyama, T and Kojima, Y and Kimura, M and Aoki, R and Ohsugi, M and Ueki, K and Miki, K and Iwata, E and Hayakawa, K and Ohmagari, N and Oka, S and Mizokami, M and Itoi, T and Kawai, T and Uemura, N and Hattori, M}, title = {Population-level Metagenomics Uncovers Distinct Effects of Multiple Medications on the Human Gut Microbiome.}, journal = {Gastroenterology}, volume = {163}, number = {4}, pages = {1038-1052}, doi = {10.1053/j.gastro.2022.06.070}, pmid = {35788347}, issn = {1528-0012}, mesh = {*Anti-Infective Agents ; Cross-Sectional Studies ; Fatty Acids, Volatile/pharmacology ; Feces/microbiology ; *Gastrointestinal Microbiome/physiology ; Humans ; Metagenomics ; *Microbiota ; }, abstract = {BACKGROUND &amp; AIMS: Medication is a major determinant of human gut microbiome structure, and its overuse increases the risks of morbidity and mortality. However, effects of certain commonly prescribed drugs and multiple medications on the gut microbiome are still underinvestigated.<br><br>METHODS: We performed shotgun metagenomic analysis of fecal samples from 4198 individuals in the Japanese 4D (Disease, Drug, Diet, Daily life) microbiome project. A total of 759 drugs were profiled, and other metadata, such as anthropometrics, lifestyles, diets, physical activities, and diseases, were prospectively collected. Second fecal samples were collected from 243 individuals to assess the effects of drug initiation and discontinuation on the microbiome.<br><br>RESULTS: We found that numerous drugs across different treatment categories influence the microbiome; more than 70% of the drugs we profiled had not been examined before. Individuals exposed to multiple drugs, polypharmacy, showed distinct gut microbiome structures harboring significantly more abundant upper gastrointestinal species and several nosocomial pathobionts due to additive drug effects. Polypharmacy was also associated with microbial functions, including the reduction of short-chain fatty acid metabolism and increased bacterial stress responses. Even nonantibiotic drugs were significantly correlated with an increased antimicrobial resistance potential through polypharmacy. Notably, a 2-time points dataset revealed the alteration and recovery of the microbiome in response to drug initiation and cessation, corroborating the observed drug-microbe associations in the cross-sectional cohort.<br><br>CONCLUSION: Our large-scale metagenomics unravels extensive and disruptive impacts of individual and multiple drug exposures on the human gut microbiome, providing a drug-microbe catalog as a basis for a deeper understanding of the role of the microbiome in drug efficacy and toxicity.}, }
@article {pmid35770164, year = {2022}, author = {Wang, J and Feng, J and Zhu, Y and Li, D and Wang, J and Chi, W}, title = {Diversity and Biogeography of Human Oral Saliva Microbial Communities Revealed by the Earth Microbiome Project.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {931065}, pmid = {35770164}, issn = {1664-302X}, abstract = {The oral cavity is an important window for microbial communication between the environment and the human body. The oral microbiome plays an important role in human health. However, compared to the gut microbiome, the oral microbiome has been poorly explored. Here, we analyzed 404 datasets from human oral saliva samples published by the Earth Microbiome Project (EMP) and compared them with 815 samples from the human gut, nose/pharynx, and skin. The diversity of the human saliva microbiome varied significantly among individuals, and the community compositions were complex and diverse. The saliva microbiome showed the lowest species diversity among the four environment types. Human oral habitats shared a small core bacterial community containing only 14 operational taxonomic units (OTUs) under 5 phyla, which occupied over 75% of the sequence abundance. For the four habitats, the core taxa of the saliva microbiome had the greatest impact on saliva habitats than other habitats and were mostly unique. In addition, the saliva microbiome showed significant differences in the populations of different regions, which may be determined by the living environment and lifestyle/dietary habits. Finally, the correlation analysis showed high similarity between the saliva microbiome and the microbiomes of Aerosol (non-saline) and Surface (non-saline), i.e., two environment types closely related to human, suggesting that contact and shared environment being the driving factors of microbial transmission. Together, these findings expand our understanding of human oral diversity and biogeography.}, }
@article {pmid35752802, year = {2022}, author = {Darcy, JL and Amend, AS and Swift, SOI and Sommers, PS and Lozupone, CA}, title = {specificity: an R package for analysis of feature specificity to environmental and higher dimensional variables, applied to microbiome species data.}, journal = {Environmental microbiome}, volume = {17}, number = {1}, pages = {34}, pmid = {35752802}, issn = {2524-6372}, support = {5 T15 LM009451-12/NH/NIH HHS/United States ; 1255972//National Science Foundation/ ; }, abstract = {BACKGROUND: Understanding the factors that influence microbes' environmental distributions is important for determining drivers of microbial community composition. These include environmental variables like temperature and pH, and higher-dimensional variables like geographic distance and host species phylogeny. In microbial ecology, "specificity" is often described in the context of symbiotic or host parasitic interactions, but specificity can be more broadly used to describe the extent to which a species occupies a narrower range of an environmental variable than expected by chance. Using a standardization we describe here, Rao's (Theor Popul Biol, 1982. https://doi.org/10.1016/0040-5809(82)90004-1, Sankhya A, 2010. https://doi.org/10.1007/s13171-010-0016-3) Quadratic Entropy can be conveniently applied to calculate specificity of a feature, such as a species, to many different environmental variables.<br><br>RESULTS: We present our R package specificity for performing the above analyses, and apply it to four real-life microbial data sets to demonstrate its application. We found that many fungi within the leaves of native Hawaiian plants had strong specificity to rainfall and elevation, even though these variables showed minimal importance in a previous analysis of fungal beta-diversity. In Antarctic cryoconite holes, our tool revealed that many bacteria have specificity to co-occurring algal community composition. Similarly, in the human gut microbiome, many bacteria showed specificity to the composition of bile acids. Finally, our analysis of the Earth Microbiome Project data set showed that most bacteria show strong ontological specificity to sample type. Our software performed as expected on synthetic data as well.<br><br>CONCLUSIONS: specificity is well-suited to analysis of microbiome data, both in synthetic test cases, and across multiple environment types and experimental designs. The analysis and software we present here can reveal patterns in microbial taxa that may not be evident from a community-level perspective. These insights can also be visualized and interactively shared among researchers using specificity's companion package, specificity.shiny.}, }
@article {pmid35744617, year = {2022}, author = {García-Mato, E and Martínez-Lamas, L and Álvarez-Fernández, M and Varela-Aneiros, I and Diniz-Freitas, M and Limeres-Posse, J and Diz-Dios, P}, title = {Molecular Detection of Streptococcus downii sp. nov. from Dental Plaque Samples from Patients with Down Syndrome and Non-Syndromic Individuals.}, journal = {Microorganisms}, volume = {10}, number = {6}, pages = {}, pmid = {35744617}, issn = {2076-2607}, abstract = {A new bacterial species has recently been identified in the dental plaque of an adolescent with Down syndrome. The species is known as Streptococcus downii sp. nov. (abbreviated to S. downii), and it inhibits the growth of S. mutans and certain periodontal pathogens. The aim of this study was to determine the distribution of S. downii in the oral cavity of individuals with Down syndrome. Methods: A specific polymerase chain reaction for the operon of bacteriocin (class IIb lactobin A/cerein 7B family) was designed to detect S. downii in individuals with Down syndrome (n = 200) and in the general population (n = 100). We also compared the whole genome of S. downii and the regions related to its bacteriocins against 127 metagenomes of supragingival plaque of the "Human Microbiome Project". Results: We detected the specific gene of the S. downii bacteriocin in an individual with Down syndrome (Cq, 34.52; GE/μL, 13.0) and in an individual of the non-syndromic control group (Cq, 34.78 Cq; GE/μL, 4.93). The prevalence of S. downii was ≤1% both in Down syndrome and in the general population, which did not allow for clinical-microbiological correlations to be established. This result was confirmed by detecting only one metagenome with an ANIm with approximately 95% homology and with 100% homology with ORFs that code class IIb lactobiocin A/cerein 7B bacteriocins among the 127 metagenomes of the "Human Microbiome Project" tested. Conclusions: The detection rate of S. downii in the supragingival dental plaque was very low, both in the Down syndrome individuals and in the non-syndromic controls. A clinical-microbiological correlation could therefore not be established.}, }
@article {pmid35713407, year = {2022}, author = {Shaffer, JP and Carpenter, CS and Martino, C and Salido, RA and Minich, JJ and Bryant, M and Sanders, K and Schwartz, T and Humphrey, G and Swafford, AD and Knight, R}, title = {A comparison of six DNA extraction protocols for 16S, ITS and shotgun metagenomic sequencing of microbial communities.}, journal = {BioTechniques}, volume = {73}, number = {1}, pages = {34-46}, pmid = {35713407}, issn = {1940-9818}, support = {R01 DK102932/DK/NIDDK NIH HHS/United States ; K12 GM068524/GM/NIGMS NIH HHS/United States ; U01 AI124316/AI/NIAID NIH HHS/United States ; DP1 AT010885/AT/NCCIH NIH HHS/United States ; U19 AG063744/AG/NIA NIH HHS/United States ; R01 HL140976/HL/NHLBI NIH HHS/United States ; R01 HL134887/HL/NHLBI NIH HHS/United States ; RF1 AG058942/AG/NIA NIH HHS/United States ; }, mesh = {Bacteria/genetics ; High-Throughput Nucleotide Sequencing/methods ; Humans ; *Metagenomics/methods ; *Microbiota/genetics ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; }, abstract = {Microbial communities contain a broad phylogenetic diversity of organisms; however, the majority of methods center on describing bacteria and archaea. Fungi are important symbionts in many ecosystems and are potentially important members of the human microbiome, beyond those that can cause disease. To expand our analysis of microbial communities to include data from the fungal internal transcribed spacer (ITS) region, five candidate DNA extraction kits were compared against our standardized protocol for describing bacteria and archaea using 16S rRNA gene amplicon- and shotgun metagenomics sequencing. The results are presented considering a diverse panel of host-associated and environmental sample types and comparing the cost, processing time, well-to-well contamination, DNA yield, limit of detection and microbial community composition among protocols. Across all criteria, the MagMAX Microbiome kit was found to perform best. The PowerSoil Pro kit performed comparably but with increased cost per sample and overall processing time. The Zymo MagBead, NucleoMag Food and Norgen Stool kits were included.}, }
@article {pmid35680554, year = {2023}, author = {Kuhl, LP and Marostica, PJC and Macedo, AJ and Kuhl, G and Siebert, M and Manica, D and Sekine, L and Schweiger, C}, title = {High microbiome variability in pediatric tracheostomy cannulas in patients with similar clinical characteristics.}, journal = {Brazilian journal of otorhinolaryngology}, volume = {89}, number = {2}, pages = {254-263}, pmid = {35680554}, issn = {1808-8686}, mesh = {RNA, Ribosomal, 16S/genetics ; *Tracheostomy ; Cannula ; *Microbiota/genetics ; Brazil ; }, abstract = {OBJECTIVES: To evaluate the bacterial microbiome found in tracheostomy cannulas of a group of children diagnosed with glossoptosis secondary to Robin Sequence (RS), and its clinical implications.<br><br>METHODS: Pediatric patients were enrolled in the study at the time of the cannula change in the hospital. During this procedure, the removed cannula was collected and stored for amplicon sequencing of 16s rRNA. DNA extraction was performed using DNeasy PowerBiofilm Kit (QIAGEN&#xae; &#x2012; Cat n&#xba; 24000-50) while sequencing was performed with the S5 (Ion S5&#x2122; System, Thermo Fisher Scientific), following Brazilian Microbiome Project (BMP) protocol.<br><br>RESULTS: All 12 patients included in the study were using tracheostomy uncuffed cannulas of the same brand, had tracheostomy performed for over 1-year and had used the removed cannula for approximately 3-months. Most abundant genera found were Aggregatibacter, Pseudomonas, Haemophilus, Neisseria, Staphylococcus, Fusobacterium, Moraxella, Streptococcus, Alloiococcus, and Capnocytophaga. Individual microbiome of each individual was highly variable, not correlating to any particular clinical characteristic.<br><br>CONCLUSION: The microbiome of tracheostomy cannulas is highly variable, even among patients with similar clinical characteristics, making it challenging to determine a standard for normality.}, }
@article {pmid35633673, year = {2022}, author = {Maestre-Carballa, L and Navarro-López, V and Martinez-Garcia, M}, title = {A Resistome Roadmap: From the Human Body to Pristine Environments.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {858831}, pmid = {35633673}, issn = {1664-302X}, abstract = {A comprehensive characterization of the human body resistome [sets of antibiotic resistance genes (ARGs)] is yet to be done and paramount for addressing the antibiotic microbial resistance threat. Here, we study the resistome of 771 samples from five major body parts (skin, nares, vagina, gut, and oral cavity) of healthy subjects from the Human Microbiome Project (HMP) and addressed the potential dispersion of ARGs in pristine environments. A total of 28,714 ARGs belonging to 235 different ARG types were found in the HMP proteome dataset (n = 9.1 × 10[7] proteins analyzed). Our study reveals a distinct resistome profile (ARG type and abundance) between body sites and high interindividual variability. Nares had the highest ARG load (≈5.4 genes/genome) followed by the oral cavity, whereas the gut showed one of the highest ARG richness (shared with nares) but the lowest abundance (≈1.3 genes/genome). The fluroquinolone resistance genes were the most abundant in the human body, followed by macrolide-lincosamide-streptogramin (MLS) or tetracycline. Most ARGs belonged to common bacterial commensals and multidrug resistance trait were predominant in the nares and vagina. Many ARGs detected here were considered as low risk for human health, whereas only a few of them, such as BlaZ, dfrA14, dfrA17, or tetM, were classified as high-risk ARG. Our data also provide hope, since the spread of common ARG from the human body to pristine environments (n = 271 samples; 77 Gb of sequencing data and 2.1 × 10[8] proteins analyzed) thus far remains very unlikely (only one case found in an autochthonous bacterium from a pristine environment). These findings broaden our understanding of ARG in the context of the human microbiome and the One-Health Initiative of WHO uniting human host-microbes and environments as a whole.}, }
@article {pmid35629064, year = {2022}, author = {Arjunan, P and Swaminathan, R}, title = {Do Oral Pathogens Inhabit the Eye and Play a Role in Ocular Diseases?.}, journal = {Journal of clinical medicine}, volume = {11}, number = {10}, pages = {}, pmid = {35629064}, issn = {2077-0383}, abstract = {Fascinatingly, the immune-privileged healthy eye has a small unique population of microbiota. The human microbiome project led to continuing interest in the ocular microbiome. Typically, ocular microflorae are commensals of low diversity that colonize the external and internal sites of the eye, without instigating any disorders. Ocular commensals modulate immunity and optimally regulate host defense against pathogenic invasion, both on the ocular surface and neuroretina. Yet, any alteration in this symbiotic relationship culminates in the perturbation of ocular homeostasis and shifts the equilibrium toward local or systemic inflammation and, in turn, impaired visual function. A compositional variation in the ocular microbiota is associated with surface disorders such as keratitis, blepharitis, and conjunctivitis. Nevertheless, innovative studies now implicate non-ocular microbial dysbiosis in glaucoma, age-related macular degeneration (AMD), uveitis, and diabetic retinopathy. Accordingly, prompt identification of the extra-ocular etiology and a methodical understanding of the mechanisms of invasion and host-microbial interaction is of paramount importance for preventative and therapeutic interventions for vision-threatening conditions. This review article aims to explore the current literature evidence to better comprehend the role of oral pathogens in the etiopathogenesis of ocular diseases, specifically AMD.}, }
@article {pmid35590169, year = {2021}, author = {Song, SJ and Wang, J and Martino, C and Jiang, L and Thompson, WK and Shenhav, L and McDonald, D and Marotz, C and Harris, PR and Hernandez, CD and Henderson, N and Ackley, E and Nardella, D and Gillihan, C and Montacuti, V and Schweizer, W and Jay, M and Combellick, J and Sun, H and Garcia-Mantrana, I and Gil Raga, F and Collado, MC and Rivera-Viñas, JI and Campos-Rivera, M and Ruiz-Calderon, JF and Knight, R and Dominguez-Bello, MG}, title = {Naturalization of the microbiota developmental trajectory of Cesarean-born neonates after vaginal seeding.}, journal = {Med (New York, N.Y.)}, volume = {2}, number = {8}, pages = {951-964.e5}, pmid = {35590169}, issn = {2666-6340}, support = {DP1 AT010885/AT/NCCIH NIH HHS/United States ; P30 DK120515/DK/NIDDK NIH HHS/United States ; }, mesh = {*Cesarean Section/adverse effects ; Citizenship ; Female ; Humans ; Infant ; Infant, Newborn ; Longitudinal Studies ; *Microbiota/genetics ; Pregnancy ; RNA, Ribosomal, 16S/genetics ; }, abstract = {BACKGROUND: Early microbiota perturbations are associated with disorders that involve immunological underpinnings. Cesarean section (CS)-born babies show altered microbiota development in relation to babies born vaginally. Here we present the first statistically powered longitudinal study to determine the effect of restoring exposure to maternal vaginal fluids after CS birth.<br><br>METHODS: Using 16S rRNA gene sequencing, we followed the microbial trajectories of multiple body sites in 177 babies over the first year of life; 98 were born vaginally, and 79 were born by CS, of whom 30 were swabbed with a maternal vaginal gauze right after birth.<br><br>FINDINGS: Compositional tensor factorization analysis confirmed that microbiota trajectories of exposed CS-born babies aligned more closely with that of vaginally born babies. Interestingly, the majority of amplicon sequence variants from maternal vaginal microbiomes on the day of birth were shared with other maternal sites, in contrast to non-pregnant women from the Human Microbiome Project (HMP) study.<br><br>CONCLUSIONS: The results of this observational study prompt urgent randomized clinical trials to test whether microbial restoration reduces the increased disease risk associated with CS birth and the underlying mechanisms. It also provides evidence of the pluripotential nature of maternal vaginal fluids to provide pioneer bacterial colonizers for the newborn body sites. This is the first study showing long-term naturalization of the microbiota of CS-born infants by restoring microbial exposure at birth.<br><br>FUNDING: C&amp;D, Emch Fund, CIFAR, Chilean CONICYT and SOCHIPE, Norwegian Institute of Public Health, Emerald Foundation, NIH, National Institute of Justice, Janssen.}, }
@article {pmid35579554, year = {2022}, author = {Sim, M and Lee, J and Wy, S and Park, N and Lee, D and Kwon, D and Kim, J}, title = {Generation and application of pseudo-long reads for metagenome assembly.}, journal = {GigaScience}, volume = {11}, number = {}, pages = {}, pmid = {35579554}, issn = {2047-217X}, mesh = {High-Throughput Nucleotide Sequencing/methods ; Humans ; *Metagenome ; Metagenomics/methods ; *Microbiota/genetics ; Sequence Analysis, DNA/methods ; }, abstract = {BACKGROUND: Metagenomic assembly using high-throughput sequencing data is a powerful method to construct microbial genomes in environmental samples without cultivation. However, metagenomic assembly, especially when only short reads are available, is a complex and challenging task because mixed genomes of multiple microorganisms constitute the metagenome. Although long read sequencing technologies have been developed and have begun to be used for metagenomic assembly, many metagenomic studies have been performed based on short reads because the generation of long reads requires higher sequencing cost than short reads.<br><br>RESULTS: In this study, we present a new method called PLR-GEN. It creates pseudo-long reads from metagenomic short reads based on given reference genome sequences by considering small sequence variations existing in individual genomes of the same or different species. When applied to a mock community data set in the Human Microbiome Project, PLR-GEN dramatically extended short reads in length of 101&#xa0;bp to pseudo-long reads with N50 of 33&#xa0;Kbp and 0.4% error rate. The use of these pseudo-long reads generated by PLR-GEN resulted in an obvious improvement of metagenomic assembly in terms of the number of sequences, assembly contiguity, and prediction of species and genes.<br><br>CONCLUSIONS: PLR-GEN can be used to generate artificial long read sequences without spending extra sequencing cost, thus aiding various studies using metagenomes.}, }
@article {pmid35562600, year = {2023}, author = {Greene, LK and McKenney, EA and Gasper, W and Wrampelmeier, C and Hayer, S and Ehmke, EE and Clayton, JB}, title = {Gut Site and Gut Morphology Predict Microbiome Structure and Function in Ecologically Diverse Lemurs.}, journal = {Microbial ecology}, volume = {85}, number = {4}, pages = {1608-1619}, pmid = {35562600}, issn = {1432-184X}, support = {PRFB 1906416//Directorate for Biological Sciences/ ; }, mesh = {Animals ; *Lemur ; Retrospective Studies ; *Lemuridae ; *Microbiota ; *Strepsirhini ; }, abstract = {Most studies of wildlife gut microbiotas understandably rely on feces to approximate consortia along the gastrointestinal tract. We therefore compared microbiome structure and predicted metagenomic function in stomach, small intestinal, cecal, and colonic samples from 52 lemurs harvested during routine necropsies. The lemurs represent seven genera (Cheirogaleus, Daubentonia, Varecia, Hapalemur, Eulemur, Lemur, Propithecus) characterized by diverse feeding ecologies and gut morphologies. In particular, the hosts variably depend on fibrous foodstuffs and show correlative morphological complexity in their large intestines. Across host lineages, microbiome diversity, variability, membership, and function differed between the upper and lower gut, reflecting regional tradeoffs in available nutrients. These patterns related minimally to total gut length but were modulated by fermentation capacity (i.e., the ratio of small to large intestinal length). Irrespective of feeding strategy, host genera with limited fermentation capacity harbored more homogenized microbiome diversity along the gut, whereas those with expanded fermentation capacity harbored cecal and colonic microbiomes with greater diversity and abundant fermentative Ruminococcaceae taxa. While highlighting the value of curated sample repositories for retrospective comparisons, our results confirm that the need to survive on fibrous foods, either routinely or in hypervariable environments, can shape the morphological and microbial features of the lower gut.}, }
@article {pmid35536037, year = {2022}, author = {Hu, C and Beyda, ND and Garey, KW}, title = {A Vancomycin HPLC Assay for Use in Gut Microbiome Research.}, journal = {Microbiology spectrum}, volume = {10}, number = {3}, pages = {e0168821}, pmid = {35536037}, issn = {2165-0497}, support = {U01 AI124290/AI/NIAID NIH HHS/United States ; }, mesh = {Anti-Bacterial Agents ; Chromatography, High Pressure Liquid/methods ; *Gastrointestinal Microbiome ; Humans ; Reproducibility of Results ; *Vancomycin/pharmacokinetics ; }, abstract = {The human microbiome project has revolutionized our understanding of the interaction between commensal microbes and human health. By far, the biggest perturbation of the microbiome involves use of broad-spectrum antibiotics excreted in the gut. Thus, pharmacodynamics of microbiome changes in relation to drug exposure pharmacokinetics is an emerging field. However, reproducibility studies are necessary to develop the field. A simple and fast high-performance liquid chromatography-photodiode array detector (HPLC) method was validated for quantitative fecal vancomycin analysis. Reproducibility of results were tested based on sample storage time, homogeneity of antibiotic within stool, and concentration consistency after lyophilization. The HPLC method enabled the complete elution of vancomycin within ~4.2 min on the reversed-phase C18 column under the isocratic elution mode, with excellent recovery (85% to 110%) over a 4-log, quantitative range (0.4-100 μg/mL). Relative standard derivations (RSD) of intra-day and inter-day results ranged from 0.4% to 5.4%. Using sample stool aliquots of various weights consistently demonstrated similar vancomycin concentrations (mean RSD: 6%; range: 2-16%). After correcting for water concentrations, vancomycin concentrations obtained after lyophilization were similar to the concentrations obtained from the original samples (RSD less than 10%). These methodologies establish sample condition standards for a quantitative HPLC to enable vancomycin pharmacokinetic studies with the human microbiome. IMPORTANCE Research on antibiotic effect on the gut microbiome is an emerging field with standardization of research methods needed. In this study, a simple and fast high-performance liquid chromatography method was validated for quantitative fecal vancomycin analysis. Reproducibility of results were tested to standardize storage time, homogeneity of antibiotic within stool, and concentration consistency after lyophilization. These methodologies establish sample condition standards for a quantitative HPLC to enable vancomycin pharmacokinetic studies with the human microbiome.}, }
@article {pmid35518360, year = {2022}, author = {Gan, R and Zhou, F and Si, Y and Yang, H and Chen, C and Ren, C and Wu, J and Zhang, F}, title = {DBSCAN-SWA: An Integrated Tool for Rapid Prophage Detection and Annotation.}, journal = {Frontiers in genetics}, volume = {13}, number = {}, pages = {885048}, pmid = {35518360}, issn = {1664-8021}, abstract = {As an intracellular form of a bacteriophage in the bacterial host genome, a prophage usually integrates into bacterial DNA with high specificity and contributes to horizontal gene transfer (HGT). With the exponentially increasing number of microbial sequences uncovered in genomic or metagenomics studies, there is a massive demand for a tool that is capable of fast and accurate identification of prophages. Here, we introduce DBSCAN-SWA, a command line software tool developed to predict prophage regions in bacterial genomes. DBSCAN-SWA runs faster than any previous tools. Importantly, it has great detection power based on analysis using 184 manually curated prophages, with a recall of 85% compared with Phage_Finder (63%), VirSorter (74%), and PHASTER (82%) for (Multi-) FASTA sequences. Moreover, DBSCAN-SWA outperforms the existing standalone prophage prediction tools for high-throughput sequencing data based on the analysis of 19,989 contigs of 400 bacterial genomes collected from Human Microbiome Project (HMP) project. DBSCAN-SWA also provides user-friendly result visualizations including a circular prophage viewer and interactive DataTables. DBSCAN-SWA is implemented in Python3 and is available under an open source GPLv2 license from https://github.com/HIT-ImmunologyLab/DBSCAN-SWA/.}, }
@article {pmid35429105, year = {2022}, author = {Li, D and Van De Werfhorst, LC and Holden, PA}, title = {Genetic sequence data evidence that human faecal-associated HF183 sequences are on human skin and in urine.}, journal = {Journal of applied microbiology}, volume = {133}, number = {2}, pages = {232-240}, pmid = {35429105}, issn = {1365-2672}, support = {//Mr. Henry (Sam) Wheeler/ ; Proposition 84//the State of California Clean Beach Initiative/ ; }, mesh = {Environmental Monitoring/methods ; Feces ; Genetic Markers ; Humans ; Polymerase Chain Reaction/methods ; RNA, Ribosomal, 16S/genetics ; *Sewage ; *Water Microbiology ; }, abstract = {AIMS: The DNA marker HF183 is a partial 16S rRNA gene sequence highly specific to human-associated Bacteroides including Bacteroides dorei. While HF183 is used to assess human faecal contamination in aquatic environments worldwide, little is known about the existence of HF183 and B. dorei in human microbiomes outside of the human gastrointestinal tract and faeces.<br><br>METHODS AND RESULTS: Previously published human skin and urine microbiome data sets from five independent human body skin studies, the Human Microbiome Project (HMP) and three independent human urine studies were analysed. The HF183 gene sequence was detected in all skin data sets, with the ratios of positive samples ranging from 0.5% to 36.3%. Popliteal fossa (knee), volar forearm and inguinal (groin) creases were identified as hot spots. HF183 was detected in two of three urine data sets, with ratios of positive samples ranging from 0% to 37.5%. All HF183-containing sequences from these data sets were classified as associated with B. dorei.<br><br>CONCLUSIONS: HF183 is widespread on human skin and present in urine.<br><br>Skin and urine microbiomes could be sources of HF183 to environmental waters. Such non-faecal sources of HF183 might explain low concentrations of HF183 in recreational waters when swimmers are present.}, }
@article {pmid35369727, year = {2022}, author = {Zhu, Q and Huang, S and Gonzalez, A and McGrath, I and McDonald, D and Haiminen, N and Armstrong, G and Vázquez-Baeza, Y and Yu, J and Kuczynski, J and Sepich-Poore, GD and Swafford, AD and Das, P and Shaffer, JP and Lejzerowicz, F and Belda-Ferre, P and Havulinna, AS and Méric, G and Niiranen, T and Lahti, L and Salomaa, V and Kim, HC and Jain, M and Inouye, M and Gilbert, JA and Knight, R}, title = {Phylogeny-Aware Analysis of Metagenome Community Ecology Based on Matched Reference Genomes while Bypassing Taxonomy.}, journal = {mSystems}, volume = {7}, number = {2}, pages = {e0016722}, pmid = {35369727}, issn = {2379-5077}, support = {RG/13/13/30194/BHF_/British Heart Foundation/United Kingdom ; DP1 AT010885/AT/NCCIH NIH HHS/United States ; U24 CA248454/CA/NCI NIH HHS/United States ; RG/18/13/33946/BHF_/British Heart Foundation/United Kingdom ; CH/12/2/29428/BHF_/British Heart Foundation/United Kingdom ; K12 GM068524/GM/NIGMS NIH HHS/United States ; F30 CA243480/CA/NCI NIH HHS/United States ; U19 AG063744/AG/NIA NIH HHS/United States ; P30 DK120515/DK/NIDDK NIH HHS/United States ; }, mesh = {Humans ; Phylogeny ; *Metagenome ; RNA, Ribosomal, 16S/genetics ; *Microbiota ; Ecology ; }, abstract = {We introduce the operational genomic unit (OGU) method, a metagenome analysis strategy that directly exploits sequence alignment hits to individual reference genomes as the minimum unit for assessing the diversity of microbial communities and their relevance to environmental factors. This approach is independent of taxonomic classification, granting the possibility of maximal resolution of community composition, and organizes features into an accurate hierarchy using a phylogenomic tree. The outputs are suitable for contemporary analytical protocols for community ecology, differential abundance, and supervised learning while supporting phylogenetic methods, such as UniFrac and phylofactorization, that are seldom applied to shotgun metagenomics despite being prevalent in 16S rRNA gene amplicon studies. As demonstrated in two real-world case studies, the OGU method produces biologically meaningful patterns from microbiome data sets. Such patterns further remain detectable at very low metagenomic sequencing depths. Compared with taxonomic unit-based analyses implemented in currently adopted metagenomics tools, and the analysis of 16S rRNA gene amplicon sequence variants, this method shows superiority in informing biologically relevant insights, including stronger correlation with body environment and host sex on the Human Microbiome Project data set and more accurate prediction of human age by the gut microbiomes of Finnish individuals included in the FINRISK 2002 cohort. We provide Woltka, a bioinformatics tool to implement this method, with full integration with the QIIME 2 package and the Qiita web platform, to facilitate adoption of the OGU method in future metagenomics studies. IMPORTANCE Shotgun metagenomics is a powerful, yet computationally challenging, technique compared to 16S rRNA gene amplicon sequencing for decoding the composition and structure of microbial communities. Current analyses of metagenomic data are primarily based on taxonomic classification, which is limited in feature resolution. To solve these challenges, we introduce operational genomic units (OGUs), which are the individual reference genomes derived from sequence alignment results, without further assigning them taxonomy. The OGU method advances current read-based metagenomics in two dimensions: (i) providing maximal resolution of community composition and (ii) permitting use of phylogeny-aware tools. Our analysis of real-world data sets shows that it is advantageous over currently adopted metagenomic analysis methods and the finest-grained 16S rRNA analysis methods in predicting biological traits. We thus propose the adoption of OGUs as an effective practice in metagenomic studies.}, }
@article {pmid35314781, year = {2022}, author = {Yu, JSL and Correia-Melo, C and Zorrilla, F and Herrera-Dominguez, L and Wu, MY and Hartl, J and Campbell, K and Blasche, S and Kreidl, M and Egger, AS and Messner, CB and Demichev, V and Freiwald, A and Mülleder, M and Howell, M and Berman, J and Patil, KR and Alam, MT and Ralser, M}, title = {Microbial communities form rich extracellular metabolomes that foster metabolic interactions and promote drug tolerance.}, journal = {Nature microbiology}, volume = {7}, number = {4}, pages = {542-555}, pmid = {35314781}, issn = {2058-5276}, support = {FC001134/ARC_/Arthritis Research UK/United Kingdom ; MC_UU_00025/11/MRC_/Medical Research Council/United Kingdom ; FC001134/CRUK_/Cancer Research UK/United Kingdom ; FC001134/WT_/Wellcome Trust/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; 200829/Z/16/Z/WT_/Wellcome Trust/United Kingdom ; FC001134/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Drug Tolerance ; Metabolic Networks and Pathways ; Metabolome ; *Microbial Interactions ; *Microbiota ; }, abstract = {Microbial communities are composed of cells of varying metabolic capacity, and regularly include auxotrophs that lack essential metabolic pathways. Through analysis of auxotrophs for amino acid biosynthesis pathways in microbiome data derived from >12,000 natural microbial communities obtained as part of the Earth Microbiome Project (EMP), and study of auxotrophic-prototrophic interactions in self-establishing metabolically cooperating yeast communities (SeMeCos), we reveal a metabolically imprinted mechanism that links the presence of auxotrophs to an increase in metabolic interactions and gains in antimicrobial drug tolerance. As a consequence of the metabolic adaptations necessary to uptake specific metabolites, auxotrophs obtain altered metabolic flux distributions, export more metabolites and, in this way, enrich community environments in metabolites. Moreover, increased efflux activities reduce intracellular drug concentrations, allowing cells to grow in the presence of drug levels above minimal inhibitory concentrations. For example, we show that the antifungal action of azoles is greatly diminished in yeast cells that uptake metabolites from a metabolically enriched environment. Our results hence provide a mechanism that explains why cells are more robust to drug exposure when they interact metabolically.}, }
@article {pmid35301322, year = {2022}, author = {Sharma, AK and Davison, S and Pafco, B and Clayton, JB and Rothman, JM and McLennan, MR and Cibot, M and Fuh, T and Vodicka, R and Robinson, CJ and Petrzelkova, K and Gomez, A}, title = {The primate gut mycobiome-bacteriome interface is impacted by environmental and subsistence factors.}, journal = {NPJ biofilms and microbiomes}, volume = {8}, number = {1}, pages = {12}, pmid = {35301322}, issn = {2055-5008}, mesh = {Animals ; Bacteria/genetics ; *Gastrointestinal Microbiome ; *Mycobiome ; Phylogeny ; Primates ; }, abstract = {The gut microbiome of primates is known to be influenced by both host genetic background and subsistence strategy. However, these inferences have been made mainly based on adaptations in bacterial composition - the bacteriome and have commonly overlooked the fungal fraction - the mycobiome. To further understand the factors that shape the gut mycobiome of primates and mycobiome-bacteriome interactions, we sequenced 16 S rRNA and ITS2 markers in fecal samples of four different nonhuman primate species and three human groups under different subsistence patterns (n = 149). The results show that gut mycobiome composition in primates is still largely unknown but highly plastic and weakly structured by primate phylogeny, compared with the bacteriome. We find significant gut mycobiome overlap between captive apes and human populations living under industrialized subsistence contexts; this is in contrast with contemporary hunter-gatherers and agriculturalists, who share more mycobiome traits with diverse wild-ranging nonhuman primates. In addition, mycobiome-bacteriome interactions were specific to each population, revealing that individual, lifestyle and intrinsic ecological factors affect structural correspondence, number, and kind of interactions between gut bacteria and fungi in primates. Our findings indicate a dominant effect of ecological niche, environmental factors, and diet over the phylogenetic background of the host, in shaping gut mycobiome composition and mycobiome-bacteriome interactions in primates.}, }
@article {pmid35273317, year = {2022}, author = {Sisti, D and Pazienza, V and Piccini, F and Citterio, B and Baffone, W and Donati Zeppa, S and Biavasco, F and Prospero, E and De Luca, A and Artico, M and Taurone, S and Minelli, A and Perri, F and Binda, E and Pracella, R and Santolini, R and Amatori, S and Sestili, P and Rocchi, MBL and Gobbi, P}, title = {A proposal for the reference intervals of the Italian microbiota "scaffold" in healthy adults.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {3952}, pmid = {35273317}, issn = {2045-2322}, mesh = {Adult ; Feces/microbiology ; Feeding Behavior ; *Gastrointestinal Microbiome/genetics ; Humans ; *Microbiota/genetics ; RNA, Ribosomal, 16S/genetics ; }, abstract = {Numerous factors, ranging from genetics, age, lifestyle, and dietary habits to local environments, contribute to the heterogeneity of the microbiota in humans. Understanding the variability of a "healthy microbiota" is a major challenge in scientific research. The gut microbiota profiles of 148 healthy Italian volunteers were examined by 16S rRNA gene sequencing to determine the range and diversity of taxonomic compositions in the gut microbiota of healthy populations. Possible driving factors were evaluated through a detailed anamnestic questionnaire. Microbiota reference intervals were also calculated. A "scaffold" of a healthy Italian gut microbiota composition was identified. Differences in relative quantitative ratios of microbiota composition were detected in two clusters: a bigger cluster (C2), which included 124 subjects, was characterized by more people from the northern Italian regions, who habitually practised more physical activity and with fewer dietary restrictions. Species richness and diversity were significantly higher in this cluster (C2) than in the other one (C1) (C1: 146.67 ± 43.67; C2: 198.17 ± 48.47; F = 23.40; P < 0.001 and C1: 16.88 ± 8.66; C2: 35.01 ± 13.40; F = 40.50; P < 0.001, respectively). The main contribution of the present study was the identification of the existence of a primary healthy microbiological framework that is only marginally affected by variations. Taken together, our data help to contextualize studies on population-specific variations, including marginal aspects, in human microbiota composition. Such variations must be related to the primary framework of a healthy microbiota and providing this perspective could help scientists to better design experimental plans and develop strategies for precision tailored microbiota modulation.}, }
@article {pmid35273169, year = {2022}, author = {Cai, YY and Huang, FQ and Lao, X and Lu, Y and Gao, X and Alolga, RN and Yin, K and Zhou, X and Wang, Y and Liu, B and Shang, J and Qi, LW and Li, J}, title = {Integrated metagenomics identifies a crucial role for trimethylamine-producing Lachnoclostridium in promoting atherosclerosis.}, journal = {NPJ biofilms and microbiomes}, volume = {8}, number = {1}, pages = {11}, pmid = {35273169}, issn = {2055-5008}, mesh = {Animals ; *Atherosclerosis ; Choline ; *Gastrointestinal Microbiome ; Humans ; Metagenomics ; Methylamines ; Mice ; }, abstract = {Microbial trimethylamine (TMA)-lyase activity promotes the development of atherosclerosis by generating of TMA, the precursor of TMA N-oxide (TMAO). TMAO is well documented, but same can not be said of TMA-producing bacteria. This work aimed to identify TMA-producing genera in human intestinal microbiota. We retrieved the genomes of human-associated microorganisms from the Human Microbiome Project database comprising 1751 genomes, Unified Human Gastrointestinal Genome collection consisting 4644 gut prokaryotes, recapitulated 4930 species-level genome bins and public gut metagenomic data of 2134 individuals from 11 populations. By sequence searching, 216 TMA-lyase-containing species from 102 genera were found to contain the homologous sequences of cntA/B, yeaW/X, and/or cutC/D. We identified 13 strains from 5 genera with cntA sequences, and 30 strains from 14 genera with cutC showing detectable relative abundance in healthy individuals. Lachnoclostridium (p = 2.9e-05) and Clostridium (p = 5.8e-04), the two most abundant cutC-containing genera, were found to be much higher in atherosclerotic patients compared with healthy persons. Upon incubation with choline (substrate), L. saccharolyticum effectively transformed it to TMA at a rate higher than 98.7% while that for C. sporogenes was 63.8-67.5% as detected by liquid chromatography-triple quadrupole mass spectrometry. In vivo studies further showed that treatment of L. saccharolyticum and choline promoted a significant increase in TMAO level in the serum of ApoE[-/-] mice with obvious accumulation of aortic plaque in same. This study discloses the significance and efficiency of the gut bacterium L. saccharolyticum in transforming choline to TMA and consequently promoting the development of atherosclerosis.}, }
@article {pmid35272051, year = {2022}, author = {Zhou, F and Gan, R and Zhang, F and Ren, C and Yu, L and Si, Y and Huang, Z}, title = {PHISDetector: A Tool to Detect Diverse In Silico Phage-host Interaction Signals for Virome Studies.}, journal = {Genomics, proteomics &amp; bioinformatics}, volume = {20}, number = {3}, pages = {508-523}, pmid = {35272051}, issn = {2210-3244}, mesh = {Humans ; *Bacteriophages/genetics ; Virome ; Prophages/genetics ; Bacteria/genetics ; *Microbiota ; }, abstract = {Phage-microbe interactions are appealing systems to study coevolution, and have also been increasingly emphasized due to their roles in human health, disease, and the development of novel therapeutics. Phage-microbe interactions leave diverse signals in bacterial and phage genomic sequences, defined as phage-host interaction signals (PHISs), which include clustered regularly interspaced short palindromic repeats (CRISPR) targeting, prophage, and protein-protein interaction signals. In the present study, we developed a novel tool phage-host interaction signal detector (PHISDetector) to predict phage-host interactions by detecting and integrating diverse in silico PHISs, and scoring the probability of phage-host interactions using machine learning models based on PHIS features. We evaluated the performance of PHISDetector on multiple benchmark datasets and application cases. When tested on a dataset of 758 annotated phage-host pairs, PHISDetector yields the prediction accuracies of 0.51 and 0.73 at the species and genus levels, respectively, outperforming other phage-host prediction tools. When applied to on 125,842 metagenomic viral contigs (mVCs) derived from 3042 geographically diverse samples, a detection rate of 54.54% could be achieved. Furthermore, PHISDetector could predict infecting phages for 85.6% of 368 multidrug-resistant (MDR) bacteria and 30% of 454 human gut bacteria obtained from the National Institutes of Health (NIH) Human Microbiome Project (HMP). The PHISDetector can be run either as a web server (http://www.microbiome-bigdata.com/PHISDetector/) for general users to study individual inputs or as a stand-alone version (https://github.com/HIT-ImmunologyLab/PHISDetector) to process massive phage contigs from virome studies.}, }
@article {pmid35181661, year = {2022}, author = {Johansen, J and Plichta, DR and Nissen, JN and Jespersen, ML and Shah, SA and Deng, L and Stokholm, J and Bisgaard, H and Nielsen, DS and Sørensen, SJ and Rasmussen, S}, title = {Genome binning of viral entities from bulk metagenomics data.}, journal = {Nature communications}, volume = {13}, number = {1}, pages = {965}, pmid = {35181661}, issn = {2041-1723}, mesh = {Bacteriophages/*classification/genetics ; Gastrointestinal Microbiome/*genetics/physiology ; Gastrointestinal Tract/*virology ; Genome, Viral/genetics ; Humans ; Metagenome/*genetics ; Metagenomics ; Virome/*genetics/physiology ; }, abstract = {Despite the accelerating number of uncultivated virus sequences discovered in metagenomics and their apparent importance for health and disease, the human gut virome and its interactions with bacteria in the gastrointestinal tract are not well understood. This is partly due to a paucity of whole-virome datasets and limitations in current approaches for identifying viral sequences in metagenomics data. Here, combining a deep-learning based metagenomics binning algorithm with paired metagenome and metavirome datasets, we develop Phages from Metagenomics Binning (PHAMB), an approach that allows the binning of thousands of viral genomes directly from bulk metagenomics data, while simultaneously enabling clustering of viral genomes into accurate taxonomic viral populations. When applied on the Human Microbiome Project 2 (HMP2) dataset, PHAMB recovered 6,077 high-quality genomes from 1,024 viral populations, and identified viral-microbial host interactions. PHAMB can be advantageously applied to existing and future metagenomes to illuminate viral ecological dynamics with other microbiome constituents.}, }
@article {pmid35178373, year = {2021}, author = {Zhang, R and Sun, J and Wang, C and Wang, X and Zhao, P and Yuan, Y and Ai, H and Zhou, Q}, title = {The Racial Disparities in the Epidemic of Metabolic Syndrome With Increased Age: A Study From 28,049 Chinese and American Adults.}, journal = {Frontiers in public health}, volume = {9}, number = {}, pages = {797183}, pmid = {35178373}, issn = {2296-2565}, mesh = {Adult ; Black or African American ; Cholesterol ; Cross-Sectional Studies ; Humans ; *Metabolic Syndrome/diagnosis/epidemiology ; Middle Aged ; Nutrition Surveys ; Obesity ; Obesity, Abdominal/diagnosis/epidemiology ; Triglycerides ; United States/epidemiology ; }, abstract = {BACKGROUND: Previous studies have revealed ethnic disparities in the prevalence of metabolic syndrome (MetS); however, the literature regarding aging-related patterns of disparities in MetS and its components remains limited.<br><br>METHODS: This cross-sectional study recruited 28,049 subjects, consisting of one Chinese race and three American races, 18-85 years of age, from the National Health and Nutrition Examination Survey (NHANES, 1999-2018) of the United States, and the Guangdong Gut Microbiome Project (GGMP, 2018) of China. MetS was defined in accordance with the National Cholesterol Education Program Adult Treatment Panel III. A modified sliding-window-based algorithm was used to depict the trajectories of the prevalence of MetS with increased age. Logistic regression analysis was performed to investigate associations between MetS and its components.<br><br>RESULTS: The prevalence of MetS increased non-linearly with age, with growth speed reaching its maximum at approximately 40-50 years. Chinese subjects exhibited a lower prevalence of MetS than non-Hispanic whites, non-Hispanic blacks, and Mexican Americans in all age groups. The two most prevalent components in Chinese subjects were reduced high-density lipoprotein cholesterol levels (42.0%) and elevated blood pressure (49.5%), and elevated triglyceride levels (36.3-49.5%) and abdominal obesity (55.8-55.9%) in Americans. Before 40 years of age, the top two MetS-associated components were abdominal obesity and elevated triglyceride levels in all races, while after 40 years, the prominent associations between MetS and its components varied among the different races and age groups.<br><br>CONCLUSIONS: Although racial disparities in the epidemic of MetS varied with increased age, abdominal obesity and elevated triglyceride levels were the top two MetS-associated components in all younger adults of different races.}, }
@article {pmid35176353, year = {2022}, author = {Mandal, S and Bandyopadhyay, S and Tyagi, K and Roy, A}, title = {Human microbial dysbiosis as driver of gynecological malignancies.}, journal = {Biochimie}, volume = {197}, number = {}, pages = {86-95}, doi = {10.1016/j.biochi.2022.02.005}, pmid = {35176353}, issn = {1638-6183}, mesh = {Biomarkers ; Dysbiosis/microbiology ; Female ; *Genital Neoplasms, Female ; Humans ; Lactobacillus ; *Microbiota ; }, abstract = {Gynecological cancers that affect female reproductive tract, remain at the top of the global cancer burden list with high relapse rate and mortality. Notwithstanding development of several novel therapeutic interventions including poly-ADP-ribose polymerase inhibitors, this family of malignancies remain deadly. The human microbiome project demonstrated that dysbiosis of health resident microflora is associated with several pathologies including malignancies of the female reproductive tract and detailed characterization of species variation and host-microbe interaction could provide clues for identification of early diagnostic biomarker, preventive and therapeutic interventions. Emerging evidence suggests that several microbial signatures are significantly associated with gynecological cancers. An increased population of Proteobacteria and Firmicutes followed by significantly reduced Lactobacilli are associated with lethal epithelial ovarian cancer. Similarly, a constant association of elevated level of Atopobium vaginae, Porphyromonas somerae, Micrococci and Gardnerella vaginalis are observed in endometrial and cervical cancers. Moreover, human papilloma virus infection significantly augments colonization of pathogenic microbes including Sneathia sanguinegens, Anaerococcus tetradius, and Peptostreptococcus anaerobius and drives carcinoma of the cervix. Interestingly, microbial dysbiosis in female reproductive tract modulates expression of several microbial and immune-responsive genes such as TLR-4, TLR-5, TLR-6 and NOD-1. Therefore, stringent investigation into the microbial dysbiosis and its underlying mechanism could provide valuable cues for identification of early diagnostic biomarker, preventive and therapeutic interventions against rogue gynecological malignancies.}, }
@article {pmid35115690, year = {2022}, author = {Lopera-Maya, EA and Kurilshikov, A and van der Graaf, A and Hu, S and Andreu-Sánchez, S and Chen, L and Vila, AV and Gacesa, R and Sinha, T and Collij, V and Klaassen, MAY and Bolte, LA and Gois, MFB and Neerincx, PBT and Swertz, MA and ,  and Harmsen, HJM and Wijmenga, C and Fu, J and Weersma, RK and Zhernakova, A and Sanna, S}, title = {Effect of host genetics on the gut microbiome in 7,738 participants of the Dutch Microbiome Project.}, journal = {Nature genetics}, volume = {54}, number = {2}, pages = {143-151}, pmid = {35115690}, issn = {1546-1718}, mesh = {ABO Blood-Group System/*genetics ; *Bacterial Physiological Phenomena ; Bifidobacterium/physiology ; Diet ; Fucosyltransferases/genetics ; *Gastrointestinal Microbiome ; Gastrointestinal Tract/*microbiology ; *Genetic Variation ; Genome, Human ; Genome-Wide Association Study ; *Host Microbial Interactions ; Humans ; Lactase/*genetics ; Metabolic Networks and Pathways ; Metagenome ; Multifactorial Inheritance ; Netherlands ; Polymorphism, Single Nucleotide ; Quantitative Trait Loci ; Sodium Chloride, Dietary ; Triglycerides/blood ; Galactoside 2-alpha-L-fucosyltransferase ; }, abstract = {Host genetics are known to influence the gut microbiome, yet their role remains poorly understood. To robustly characterize these effects, we performed a genome-wide association study of 207 taxa and 205 pathways representing microbial composition and function in 7,738 participants of the Dutch Microbiome Project. Two robust, study-wide significant (P < 1.89 × 10[-10]) signals near the LCT and ABO genes were found to be associated with multiple microbial taxa and pathways and were replicated in two independent cohorts. The LCT locus associations seemed modulated by lactose intake, whereas those at ABO could be explained by participant secretor status determined by their FUT2 genotype. Twenty-two other loci showed suggestive evidence (P < 5 × 10[-8]) of association with microbial taxa and pathways. At a more lenient threshold, the number of loci we identified strongly correlated with trait heritability, suggesting that much larger sample sizes are needed to elucidate the remaining effects of host genetics on the gut microbiome.}, }
@article {pmid37938691, year = {2022}, author = {Jorge, F and Brealey, JC and Brindley, PJ and Buysse, M and Cantacessi, C and Duron, O and Fichorova, R and Fitzpatrick, CR and Hahn, M and Hunter, C and Hervé, V and Knoll, LJ and Kohl, KD and Lalle, M and Lukeš, J and Martínez, JM and Perkins, SL and Poulin, R and Rosario, K and Schneider, AC and Schriml, LM and Thompson, LR and Walls, RL and Dheilly, NM}, title = {MIxS-SA: a MIxS extension defining the minimum information standard for sequence data from symbiont-associated micro-organisms.}, journal = {ISME communications}, volume = {2}, number = {1}, pages = {9}, pmid = {37938691}, issn = {2730-6151}, support = {R01 AI144016/AI/NIAID NIH HHS/United States ; R01 CA164719/CA/NCI NIH HHS/United States ; }, abstract = {The symbiont-associated (SA) environmental package is a new extension to the minimum information about any (x) sequence (MIxS) standards, established by the Parasite Microbiome Project (PMP) consortium, in collaboration with the Genomics Standard Consortium. The SA was built upon the host-associated MIxS standard, but reflects the nestedness of symbiont-associated microbiota within and across host-symbiont-microbe interactions. This package is designed to facilitate the collection and reporting of a broad range of metadata information that apply to symbionts such as life history traits, association with one or multiple host organisms, or the nature of host-symbiont interactions along the mutualism-parasitism continuum. To better reflect the inherent nestedness of all biological systems, we present a novel feature that allows users to co-localize samples, to nest a package within another package, and to identify replicates. Adoption of the MIxS-SA and of the new terms will facilitate reports of complex sampling design from a myriad of environments.}, }
@article {pmid35091681, year = {2022}, author = {Saliba, J and Coutaud, B and Makhani, K and Epstein Roth, N and Jackson, J and Park, JY and Gagnon, N and Costa, P and Jeyakumar, T and Bury, M and Beauchemin, N and Mann, KK and Blank, V}, title = {Loss of NFE2L3 protects against inflammation-induced colorectal cancer through modulation of the tumor microenvironment.}, journal = {Oncogene}, volume = {41}, number = {11}, pages = {1563-1575}, pmid = {35091681}, issn = {1476-5594}, support = {MOP-97932//CIHR/Canada ; PJT-152937//CIHR/Canada ; }, mesh = {Animals ; Basic-Leucine Zipper Transcription Factors/metabolism ; *Colorectal Neoplasms/genetics ; Forkhead Transcription Factors ; Humans ; Inflammation/genetics ; Interleukin-33 ; Mice ; T-Lymphocytes, Regulatory ; *Tumor Microenvironment/genetics ; }, abstract = {We investigated the role of the NFE2L3 transcription factor in inflammation-induced colorectal cancer. Our studies revealed that Nfe2l3[-/-] mice exhibit significantly less inflammation in the colon, reduced tumor size and numbers, and skewed localization of tumors with a more pronounced decrease of tumors in the distal colon. CIBERSORT analysis of RNA-seq data from normal and tumor tissue predicted a reduction in mast cells in Nfe2l3[-/-] animals, which was confirmed by toluidine blue staining. Concomitantly, the transcript levels of Il33 and Rab27a, both important regulators of mast cells, were reduced and increased, respectively, in the colorectal tumors of Nfe2l3[-/-] mice. Furthermore, we validated NFE2L3 binding to the regulatory sequences of the IL33 and RAB27A loci in human colorectal carcinoma cells. Using digital spatial profiling, we found that Nfe2l3[-/-] mice presented elevated FOXP3 and immune checkpoint markers CTLA4, TIM3, and LAG3, suggesting an increase in Treg counts. Staining for CD3 and FOXP3 confirmed a significant increase in immunosuppressive Tregs in the colon of Nfe2l3[-/-] animals. Also, Human Microbiome Project (HMP2) data showed that NFE2L3 transcript levels are higher in the rectum of ulcerative colitis patients. The observed changes in the tumor microenvironment provide new insights into the molecular differences regarding colon cancer sidedness. This may be exploited for the treatment of early-onset colorectal cancer as this emerging subtype primarily displays distal/left-sided tumors.}, }
@article {pmid35078284, year = {2022}, author = {Su, Z and Jia, X and Fan, Y and Zhao, F and Qiao, Y}, title = {[Progress of Research on the Relationship between Lung Microbiome and Lung Cancer].}, journal = {Zhongguo fei ai za zhi = Chinese journal of lung cancer}, volume = {25}, number = {1}, pages = {40-45}, pmid = {35078284}, issn = {1999-6187}, mesh = {Humans ; Lung ; Lung Diseases ; *Lung Neoplasms ; *Microbiota ; Oncogenes ; }, abstract = {The microbiota plays an important role in the biological functions of the human body and is associated with various disease states such as inflammation (gastritis, hepatitis) and cancer (stomach, cervical, liver). The Human Microbiome Project painted a panorama of human microorganisms in its first phase, incorporating body parts such as the nasal cavity, oral cavity, intestine, vagina and skin, while the lungs were considered a sterile environment. However, studies in recent years have confirmed the presence of a rich microbial community in the lung, and the association of this lung microbiota with lung disease has become a hot topic of research. Current research has found that patients with lung cancer have a specific microbiota compared to healthy individuals or patients with lung disease. Even in patients with lung cancer, a lung microbiota specific to the tumor site is present. In addition, different pathological types and metastatic status of lung cancer can lead to differences in microbiota. Mechanistic studies have found that the lung microbiota may influence lung cancer development by affecting the immune response. Clinical studies on lung microbiota and immunotherapy are still in the preliminary stage. More relevant studies are needed in the future to provide high-quality evidence to further understand the oncogenic mechanisms of lung microbiota and provide new ideas for clinical treatment. This paper briefly reviews the progress of lung microbiota research in terms of its relevance to lung cancer, possible molecular mechanisms and applications in clinical treatment, and provides an outlook for future research. .}, }
@article {pmid35058973, year = {2021}, author = {Liu, B and Huang, L and Liu, Z and Pan, X and Cui, Z and Pan, J and Xie, L}, title = {EasyMicroPlot: An Efficient and Convenient R Package in Microbiome Downstream Analysis and Visualization for Clinical Study.}, journal = {Frontiers in genetics}, volume = {12}, number = {}, pages = {803627}, pmid = {35058973}, issn = {1664-8021}, abstract = {Advances in next-generation sequencing (NGS) have revolutionized microbial studies in many fields, especially in clinical investigation. As the second human genome, microbiota has been recognized as a new approach and perspective to understand the biological and pathologic basis of various diseases. However, massive amounts of sequencing data remain a huge challenge to researchers, especially those who are unfamiliar with microbial data analysis. The mathematic algorithm and approaches introduced from another scientific field will bring a bewildering array of computational tools and acquire higher quality of script experience. Moreover, a large cohort research together with extensive meta-data including age, body mass index (BMI), gender, medical results, and others related to subjects also aggravate this situation. Thus, it is necessary to develop an efficient and convenient software for clinical microbiome data analysis. EasyMicroPlot (EMP) package aims to provide an easy-to-use microbial analysis tool based on R platform that accomplishes the core tasks of metagenomic downstream analysis, specially designed by incorporation of popular microbial analysis and visualization used in clinical microbial studies. To illustrate how EMP works, 694 bio-samples from Guangdong Gut Microbiome Project (GGMP) were selected and analyzed with EMP package. Our analysis demonstrated the influence of dietary style on gut microbiota and proved EMP package's powerful ability and excellent convenience to address problems for this field.}, }
@article {pmid35054168, year = {2021}, author = {Gouello, A and Dunyach-Remy, C and Siatka, C and Lavigne, JP}, title = {Analysis of Microbial Communities: An Emerging Tool in Forensic Sciences.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {12}, number = {1}, pages = {}, pmid = {35054168}, issn = {2075-4418}, abstract = {The objective of forensic sciences is to find clues in a crime scene in order to reconstruct the scenario. Classical samples include DNA or fingerprints, but both have inherent limitations and can be uninformative. Another type of sample has emerged recently in the form of the microbiome. Supported by the Human Microbiome Project, the characteristics of the microbial communities provide real potential in forensics. They are highly specific and can be used to differentiate and classify the originating body site of a human biological trace. Skin microbiota is also highly specific and different between individuals, leading to its possibility as an identification tool. By extension, the possibilities of the microbial communities to be deposited on everyday objects has also been explored. Other uses include the determination of the post-mortem interval or the analysis of soil communities. One challenge is that the microbiome changes over time and can be influenced by many environmental and lifestyle factors. This review offers an overview of the main methods and applications to demonstrate the benefit of the microbiome to provide forensically relevant information.}, }
@article {pmid35008909, year = {2022}, author = {Popkov, VA and Zharikova, AA and Demchenko, EA and Andrianova, NV and Zorov, DB and Plotnikov, EY}, title = {Gut Microbiota as a Source of Uremic Toxins.}, journal = {International journal of molecular sciences}, volume = {23}, number = {1}, pages = {}, pmid = {35008909}, issn = {1422-0067}, support = {21-75-30009//Russian Science Foundation/ ; }, mesh = {Animals ; Bacteria/metabolism ; Cluster Analysis ; Enzymes/metabolism ; *Gastrointestinal Microbiome ; Humans ; Metadata ; RNA, Messenger/genetics/metabolism ; Uremic Toxins/*metabolism ; }, abstract = {Uremic retention solutes are the compounds that accumulate in the blood when kidney excretory function is impaired. Some of these compounds are toxic at high concentrations and are usually known as "uremic toxins". The cumulative detrimental effect of uremic toxins results in numerous health problems and eventually mortality during acute or chronic uremia, especially in end-stage renal disease. More than 100 different solutes increase during uremia; however, the exact origin for most of them is still debatable. There are three main sources for such compounds: exogenous ones are consumed with food, whereas endogenous ones are produced by the host metabolism or by symbiotic microbiota metabolism. In this article, we identify uremic retention solutes presumably of gut microbiota origin. We used database analysis to obtain data on the enzymatic reactions in bacteria and human organisms that potentially yield uremic retention solutes and hence to determine what toxins could be synthesized in bacteria residing in the human gut. We selected biochemical pathways resulting in uremic retention solutes synthesis related to specific bacterial strains and revealed links between toxin concentration in uremia and the proportion of different bacteria species which can synthesize the toxin. The detected bacterial species essential for the synthesis of uremic retention solutes were then verified using the Human Microbiome Project database. Moreover, we defined the relative abundance of human toxin-generating enzymes as well as the possibility of the synthesis of a particular toxin by the human metabolism. Our study presents a novel bioinformatics approach for the elucidation of the origin of both uremic retention solutes and uremic toxins and for searching for the most likely human microbiome producers of toxins that can be targeted and used for the therapy of adverse consequences of uremia.}, }
@article {pmid34988495, year = {2021}, author = {Stanislawski, MA and Stamper, CE and Stearns-Yoder, KA and Hoisington, AJ and Brostow, DP and Forster, JE and Postolache, TT and Lowry, CA and Brenner, LA}, title = {Characterization of the gut microbiota among Veterans with unique military-related exposures and high prevalence of chronic health conditions: A United States-Veteran Microbiome Project (US-VMP) study.}, journal = {Brain, behavior, &amp; immunity - health}, volume = {18}, number = {}, pages = {100346}, pmid = {34988495}, issn = {2666-3546}, abstract = {The gut microbiome is impacted by environmental exposures and has been implicated in many physical and mental health conditions, including anxiety disorders, affective disorders, and trauma- and stressor-related disorders such as posttraumatic stress disorder (PTSD). United States (US) military Veterans are a unique population in that their military-related exposures can have consequences for both physical and mental health, but the gut microbiome of this population has been understudied. In this publication, we describe exposures, health conditions, and medication use of Veterans in the US Veteran Microbiome Project (US-VMP) and examine the associations between these characteristics and the gut microbiota. This cohort included 331 US Veterans seeking healthcare with the Veterans Health Administration who were 83% male with an average (±SD) age of 47.6 ± 13.4 years. The cohort displayed a high prevalence of PTSD (49.8%) and history of traumatic brain injuries (76.1%), and high current use of prescription medications (74.9%) to treat various acute and chronic conditions. We observed significant associations between the gut microbiota composition and gastroenteritis, peripheral vascular disease (PVD), bipolar disorders, symptoms of severe depression based on the Beck Depression Inventory, stimulant and opioid use disorders, beta-blockers, serotonin and norepinephrine reuptake inhibitor antidepressants, diabetes medications, and proton pump inhibitors. Many of the Veteran characteristics examined were associated with altered relative abundances of specific taxa. We found that PVD and cardiovascular disease were associated with lower microbiota diversity in the gut (i.e., α-diversity), while supplemental vitamin use was associated with higher α-diversity. Our study contributes novel insights as to whether the unique exposures of Veterans in this cohort correlate with gut microbiota characteristics and, in line with previous findings with other population-level studies of the microbiome, confirms associations between numerous health conditions and medications with the gut microbiome.}, }
@article {pmid34963427, year = {2022}, author = {Fromentin, M and Bridier-Nahmias, A and Legoff, J and Mercier-Delarue, S and Ranger, N and Vuillard, C and Do Vale, J and Zucman, N and Alberdi, A and Ricard, JD and Roux, D}, title = {The 16S rRNA lung microbiome in mechanically ventilated patients: a methodological study.}, journal = {Experimental lung research}, volume = {48}, number = {1}, pages = {23-34}, doi = {10.1080/01902148.2021.2021327}, pmid = {34963427}, issn = {1521-0499}, mesh = {Bacteria/genetics ; High-Throughput Nucleotide Sequencing/methods ; Humans ; Lung ; *Microbiota/genetics ; RNA, Ribosomal, 16S/genetics ; *Respiration, Artificial/adverse effects ; }, abstract = {Characterization of the respiratory tract bacterial microbiome is in its infancy when compared to the gut microbiota. To limit bias mandates a robust methodology. Specific amplification of the hypervariable (V) region of the 16SrRNA gene is a crucial step. Differences in accuracy exist for one V region to another depending on the sampled environment. We aimed to assess the impact of the primer sequences targeting the V4 region currently used for gut microbiota studies in respiratory samples. Materials and methods: The original 515 F-806R primer pair targets the V4 region of the 16SrRNA gene. We compared two different 515 F-806R primer pairs before Illumina 250 paired-end sequencing for bacterial microbiome analyses of respiratory samples from critically-ill ventilated patients. "S-V4" for "Stringent V4" primer pair is used in two ongoing international projects "the Integrative Human microbiome project (iHMP)" and "the Earth microbiome project (EMP)." "R-V4" for "Relaxed V4" primer pair has been modified to reduce biases against specific environmental taxa. The optimal method was determined by concordance with conventional microbiology. Results: Twenty samples from three patients who developed a ventilator-associated pneumonia (VAP) and four who did not (control ventilated patients) were sequenced. Highly different results were obtained. "S-V4" provided the best agreement with the conventional microbiology for endotracheal aspirate: 89% as compared to 56% for "R-V4." The main difference related to poor Enterobacteriaceae detection with "R-V4" primers. Conclusions: Accuracy of the bacterial lung microbiome composition was highly dependent on the primers used for amplification of the 16 s rRNA hypervariable sequence. This work validates for future lung microbiome studies the use of the 515 F-806R "S-V4" primer pair associated to Illumina® MiSeq paired-end sequencing.}, }
@article {pmid34944176, year = {2021}, author = {Eschweiler, K and Clayton, JB and Moresco, A and McKenney, EA and Minter, LJ and Suhr Van Haute, MJ and Gasper, W and Hayer, SS and Zhu, L and Cooper, K and Ange-van Heugten, K}, title = {Host Identity and Geographic Location Significantly Affect Gastrointestinal Microbial Richness and Diversity in Western Lowland Gorillas (Gorilla gorilla gorilla) under Human Care.}, journal = {Animals : an open access journal from MDPI}, volume = {11}, number = {12}, pages = {}, pmid = {34944176}, issn = {2076-2615}, abstract = {The last few decades have seen an outpouring of gastrointestinal (GI) microbiome studies across diverse host species. Studies have ranged from assessments of GI microbial richness and diversity to classification of novel microbial lineages. Assessments of the "normal" state of the GI microbiome composition across multiple host species has gained increasing importance for distinguishing healthy versus diseased states. This study aimed to determine baselines and trends over time to establish "typical" patterns of GI microbial richness and diversity, as well as inter-individual variation, in three populations of western lowland gorillas (Gorilla gorilla gorilla) under human care at three zoological institutions in North America. Fecal samples were collected from 19 western lowland gorillas every two weeks for seven months (n = 248). Host identity and host institution significantly affected GI microbiome community composition (p < 0.05), although host identity had the most consistent and significant effect on richness (p = 0.03) and Shannon diversity (p = 0.004) across institutions. Significant changes in microbial abundance over time were observed only at Denver Zoo (p < 0.05). Our results suggest that individuality contributes to most of the observed GI microbiome variation in the study populations. Our results also showed no significant changes in any individual's microbial richness or Shannon diversity during the 7-month study period. While some microbial taxa (Prevotella, Prevotellaceae and Ruminococcaceae) were detected in all gorillas at varying levels, determining individual baselines for microbial composition comparisons may be the most useful diagnostic tool for optimizing non-human primate health under human care.}, }
@article {pmid34940122, year = {2021}, author = {Ghannoum, MA and McCormick, TS and Retuerto, M and Bebek, G and Cousineau, S and Hartman, L and Barth, C and Schrom, K}, title = {Evaluation of Microbiome Alterations Following Consumption of BIOHM, a Novel Probiotic.}, journal = {Current issues in molecular biology}, volume = {43}, number = {3}, pages = {2135-2146}, pmid = {34940122}, issn = {1467-3045}, support = {R01 AI145289/AI/NIAID NIH HHS/United States ; AI145289//National Institute of Allergy and Infectious Diseases/ ; }, mesh = {Candida albicans ; Dysbiosis/*microbiology ; Healthy Volunteers ; Humans ; Metagenomics/methods ; Microbial Interactions ; *Microbiota ; Mycobiome ; Probiotics/*administration &amp; dosage ; RNA, Ribosomal, 16S ; }, abstract = {Gastrointestinal microbiome dysbiosis may result in harmful effects on the host, including those caused by inflammatory bowel diseases (IBD). The novel probiotic BIOHM, consisting of Bifidobacterium breve, Saccharomyces boulardii, Lactobacillus acidophilus, L. rhamnosus, and amylase, was developed to rebalance the bacterial-fungal gut microbiome, with the goal of reducing inflammation and maintaining a healthy gut population. To test the effect of BIOHM on human subjects, we enrolled a cohort of 49 volunteers in collaboration with the Fermentation Festival group (Santa Barbara, CA, USA). The profiles of gut bacterial and fungal communities were assessed via stool samples collected at baseline and following 4 weeks of once-a-day BIOHM consumption. Mycobiome analysis following probiotic consumption revealed an increase in Ascomycota levels in enrolled individuals and a reduction in Zygomycota levels (p value < 0.01). No statistically significant difference in Basidiomycota was detected between pre- and post-BIOHM samples and control abundance profiles (p > 0.05). BIOHM consumption led to a significant reduction in the abundance of Candida genus in tested subjects (p value < 0.013), while the abundance of C. albicans also trended lower than before BIOHM use, albeit not reaching statistical significance. A reduction in the abundance of Firmicutes at the phylum level was observed following BIOHM use, which approached levels reported for control individuals reported in the Human Microbiome Project data. The preliminary results from this clinical study suggest that BIOHM is capable of significantly rebalancing the bacteriome and mycobiome in the gut of healthy individuals, suggesting that further trials examining the utility of the BIOHM probiotic in individuals with gastrointestinal symptoms, where dysbiosis is considered a source driving pathogenesis, are warranted.}, }
@article {pmid34928256, year = {2022}, author = {Verstraelen, H and Vieira-Baptista, P and De Seta, F and Ventolini, G and Lonnee-Hoffmann, R and Lev-Sagie, A}, title = {The Vaginal Microbiome: I. Research Development, Lexicon, Defining "Normal" and the Dynamics Throughout Women's Lives.}, journal = {Journal of lower genital tract disease}, volume = {26}, number = {1}, pages = {73-78}, pmid = {34928256}, issn = {1526-0976}, mesh = {Adolescent ; Bacteria ; Female ; Humans ; Infant, Newborn ; Menopause ; *Microbiota ; Research ; Vagina ; }, abstract = {OBJECTIVE: This series of articles, titled The Vaginal Microbiome, written on behalf of the International Society for the Study of Vulvovaginal Disease, aims to summarize the current findings and understanding of the vaginal bacterial microbiota, mainly regarding areas relevant to clinicians specializing in vulvovaginal disorders.<br><br>MATERIALS AND METHODS: A database search of PubMed was performed, using the search terms "vaginal microbiome" (VMB) with "research," "normal," "neonate," "puberty," "adolescent," "menopause," and "ethnicities," as well as "human microbiome project." Full article texts were reviewed. Reference lists were screened for additional articles.<br><br>RESULTS: In the last 2 decades, many studies applying molecular techniques were performed, intending to characterize the vaginal microbiota. These studies advanced our understanding of how vaginal health is defined. The first article in this series focuses on the advancement of VMB research, technical definitions, the definition of "normal" VMB, and the dynamics of VMB throughout women's lives.<br><br>CONCLUSIONS: Understanding how microorganisms inhabiting the vagina interact with each other and with the host is important for a more complete understanding of vaginal health. The clinical application of microbial community sequencing is in its beginning, and its interpretation regarding practical clinical aspects is yet to be determined.}, }
@article {pmid34880965, year = {2022}, author = {Barb, JJ and Maki, KA and Kazmi, N and Meeks, BK and Krumlauf, M and Tuason, RT and Brooks, AT and Ames, NJ and Goldman, D and Wallen, GR}, title = {The oral microbiome in alcohol use disorder: a longitudinal analysis during inpatient treatment.}, journal = {Journal of oral microbiology}, volume = {14}, number = {1}, pages = {2004790}, pmid = {34880965}, issn = {2000-2297}, abstract = {BACKGROUND: Alcohol use disorder (AUD)-induced disruption of oral microbiota can lead to poor oral health; there have been no studies published examining the longitudinal effects of alcohol use cessation on the oral microbiome.<br><br>AIM: To investigate the oral microbiome during alcohol cessation during inpatient treatment for AUD.<br><br>METHODS: Up to 10 oral tongue brushings were collected from 22 AUD patients during inpatient treatment at the National Institutes of Health. Alcohol use history, smoking, and periodontal disease status were measured. Oral microbiome samples were sequenced using 16S rRNA gene sequencing.<br><br>RESULTS: Alpha diversity decreased linearly during treatment across the entire cohort (P =&#xa0;0.002). Alcohol preference was associated with changes in both alpha and beta diversity measures. Characteristic tongue dorsum genera from the Human Microbiome Project such as Streptococcus, Prevotella, Veillonella and Haemophilus were highly correlated in AUD. Oral health-associated genera that changed longitudinally during abstinence included Actinomyces, Capnocytophaga, Fusobacterium, Neisseria and Prevotella.<br><br>CONCLUSION: The oral microbiome in AUD is affected by alcohol preference. Patients with AUD often have poor oral health but abstinence and attention to oral care improve dysbiosis, decreasing microbiome diversity and periodontal disease-associated genera while improving acute oral health.}, }
@article {pmid34874775, year = {2021}, author = {Zhang, Z and Liu, Y and Zhang, P and Wang, J and Li, D and Li, YZ}, title = {PAAR Proteins Are Versatile Clips That Enrich the Antimicrobial Weapon Arsenals of Prokaryotes.}, journal = {mSystems}, volume = {6}, number = {6}, pages = {e0095321}, pmid = {34874775}, issn = {2379-5077}, support = {2017FY100300//Special Investigation on Scientific and Technological Basic Resources/ ; 2018YFA0900400//National Key Research and Development Program/ ; 2018GSF121015//Key Research and Development Program of Shandong Province/ ; 2020GN113//Fundamental Research Funds of Shandong University/ ; 32070030//National Natural Science Foundation of China (NSFC)/ ; BK20190199//Natural Science Foundation of Jiangsu Province (Jiangsu Natural Science Foundation)/ ; }, abstract = {Protein toxins secreted by prokaryotes have been found to affect the pathogenicity of pathogens or directly mediate antagonistic interactions between prokaryotes. PAAR proteins are important carriers of toxic effectors and are located at the forefront of either the type VI secretion system (T6SS) or the extracellular contractile injection system (eCIS). This study systematically investigated PAAR homologues and related toxic effectors. We found that PAAR homologues were divided into 8 types and 16 subtypes and distributed in 23.1% of bacterial genomes and 7.8% of archaeal genomes. PAAR proteins of all types fold into a highly similar conical structure, even from relatively diverse underlying sequences. PAAR homologues associated with different secretion systems display a mixed phylogenetic relationship, indicating that PAAR proteins from such a subtype can be assembled on either a T6SS or an eCIS. More than 1,300 PAAR-related toxic effector genes were identified; one PAAR subtype can be associated with toxins of over 40 families, and toxins from one family can be associated with more than 10 PAAR subtypes. A large-scale comparison of Earth Microbiome Project data and prokaryotic genomes revealed that prokaryotes encoding PAAR genes are widely present in diverse environments worldwide, and taxa encoding multiple PAAR gene copies exhibit a wider distribution in environments than other taxa. Overall, our studies highlighted that PAAR proteins are versatile clips loaded with antimicrobial toxin bullets for secretion weapons (T6SS and eCIS), greatly enriching the weapon arsenal of prokaryotes, which, often together with VgrG, help prokaryotes fight for survival advantages in crowded environments. IMPORTANCE Infectious diseases caused by microbial pathogens are severe threats to human health and economic development. To respond to these threats, it is necessary to understand how microorganisms survive in and adapt to complex environments. Microorganic toxins, which are widely distributed in nature, are the key weapons in life domain interactions. PAAR proteins are important carriers of prokaryotic toxic effectors. We reveal the versatility of PAAR proteins between secretory systems and the massive diversity of toxic effectors carried by PAAR proteins, which helps prokaryotes enrich their arsenal and expand their ability to attack their neighbors. A large number of PAAR homologues and related toxic effectors enhance the survival competitiveness of prokaryotic populations. In conclusion, our work provides an example for large-scale analysis of the global distribution and ecological functions of prokaryotic functional genes.}, }
@article {pmid34841779, year = {2021}, author = {Yin, Y and Yu, R and Chen, H}, title = {[Shotgun metagenome sequencing of Chinese gut microbiota: a review].}, journal = {Sheng wu gong cheng xue bao = Chinese journal of biotechnology}, volume = {37}, number = {11}, pages = {3717-3733}, doi = {10.13345/j.cjb.210556}, pmid = {34841779}, issn = {1872-2075}, mesh = {China ; *Gastrointestinal Microbiome/genetics ; Humans ; Metagenome ; *Microbiota ; RNA, Ribosomal, 16S/genetics ; United States ; }, abstract = {The research on the relationship between gut microbiota and human health continues to be a hot topic in the field of life science. Culture independent 16S rRNA gene high-throughput sequencing is the current main research method. However, with the reduction of sequencing cost and the maturity of data analysis methods, shotgun metagenome sequencing is gradually becoming an important method for the study of gut microbiome due to its advantages of obtaining more information. With the support from the human microbiome project, 30 805 metagenome samples were sequenced in the United States. By searching NCBI PubMed and SRA databases, it was found that 72 studies collecting about 10 000 Chinese intestinal samples were used for metagenome sequencing. To date, only 56 studies were published, including 16 related to metabolic diseases, 16 related to infectious and immune diseases, and 12 related to cardiovascular and cerebrovascular diseases. The samples were mainly collected in Beijing, Guangzhou, Shanghai and other cosmopolitan cities, where great differences exist in sequencing platforms and methods. The outcome of most studies are based on correlation analysis, which has little practical value in guiding the diagnosis and treatment of clinical diseases. Standardizing sampling methods, sequencing platform and data analysis process, and carrying out multi center parallel research will contribute to data integration and comparative analysis. Moreover, insights into the functional verification and molecular mechanism by using the combination of transcriptomics, proteomics and culturomics will enable the gut microbiota research to better serve the clinical diagnosis and treatment.}, }
@article {pmid34820530, year = {2021}, author = {Liang, G}, title = {Altered gut bacterial and metabolic signatures and their interaction in inflammatory bowel disease.}, journal = {Synthetic and systems biotechnology}, volume = {6}, number = {4}, pages = {377-383}, pmid = {34820530}, issn = {2405-805X}, abstract = {Dysregulation of the gut microbiome has been implicated in the progression of many diseases. This study explored the role of microbial and metabolic signatures, and their interaction between the Human inflammatory bowel disease (IBD) and healthy controls (HCs) based on the combination of machine learning and traditional statistical analysis, using data collected from the Human Microbiome Project (HMP) and the Integrative Human Microbiome Project (iHMP). It was showed that the microbial and metabolic signatures of IBD patients were significantly different from those of HCs. Compared to HCs, IBD subjects were characterized by 25 enriched species and 6 depleted species. Furthermore, a total of 17 discriminative pathways were identified between the IBD and HC groups. Those differential pathways were mainly involved in amino acid, nucleotide biosynthesis, and carbohydrate degradation. Notably, co-occurrence network analysis revealed that non-predominant bacteria Ruminococcus_obeum and predominant bacteria Faecalibacterium_prausnitzii formed the same broad and strong co-occurring relationships with pathways. Moreover, the essay identified a combinatorial marker panel that could distinguish IBD from HCs. Receiver Operating Characteristic (ROC) and Decision Curve Analysis (DCA) confirmed the high accuracy (AUC = 0.966) and effectiveness of the model. Meanwhile, an independent cohort used for external validation also showed the identical high efficacy (AUC = 0.835). These findings showed that the gut microbes may be relevant to the pathogenesis and pathophysiology, and offer universal utility as a non-invasive diagnostic test in IBD.}, }
@article {pmid34718406, year = {2022}, author = {Liu, T and Xu, P and Du, Y and Lu, H and Zhao, H and Wang, T}, title = {MZINBVA: variational approximation for multilevel zero-inflated negative-binomial models for association analysis in microbiome surveys.}, journal = {Briefings in bioinformatics}, volume = {23}, number = {1}, pages = {}, doi = {10.1093/bib/bbab443}, pmid = {34718406}, issn = {1477-4054}, mesh = {Computer Simulation ; Humans ; *Microbiota ; Models, Statistical ; Research Design ; }, abstract = {As our understanding of the microbiome has expanded, so has the recognition of its critical role in human health and disease, thereby emphasizing the importance of testing whether microbes are associated with environmental factors or clinical outcomes. However, many of the fundamental challenges that concern microbiome surveys arise from statistical and experimental design issues, such as the sparse and overdispersed nature of microbiome count data and the complex correlation structure among samples. For example, in the human microbiome project (HMP) dataset, the repeated observations across time points (level 1) are nested within body sites (level 2), which are further nested within subjects (level 3). Therefore, there is a great need for the development of specialized and sophisticated statistical tests. In this paper, we propose multilevel zero-inflated negative-binomial models for association analysis in microbiome surveys. We develop a variational approximation method for maximum likelihood estimation and inference. It uses optimization, rather than sampling, to approximate the log-likelihood and compute parameter estimates, provides a robust estimate of the covariance of parameter estimates and constructs a Wald-type test statistic for association testing. We evaluate and demonstrate the performance of our method using extensive simulation studies and an application to the HMP dataset. We have developed an R package MZINBVA to implement the proposed method, which is available from the GitHub repository https://github.com/liudoubletian/MZINBVA.}, }
@article {pmid34708327, year = {2021}, author = {de Medeiros Azevedo, T and Aburjaile, FF and Ferreira-Neto, JRC and Pandolfi, V and Benko-Iseppon, AM}, title = {The endophytome (plant-associated microbiome): methodological approaches, biological aspects, and biotech applications.}, journal = {World journal of microbiology &amp; biotechnology}, volume = {37}, number = {12}, pages = {206}, pmid = {34708327}, issn = {1573-0972}, mesh = {Agricultural Inoculants ; Agriculture ; Biotechnology/*methods ; Computational Biology ; *Endophytes ; Humans ; Metagenomics/methods ; *Microbiota ; Plant Roots/microbiology ; Plants/*microbiology ; Soil ; Soil Microbiology ; }, abstract = {Similar to other organisms, plants establish interactions with a variety of microorganisms in their natural environment. The plant microbiome occupies the host plant's tissues, either internally or on its surfaces, showing interactions that can assist in its growth, development, and adaptation to face environmental stresses. The advance of metagenomics and metatranscriptomics approaches has strongly driven the study and recognition of plant microbiome impacts. Research in this regard provides comprehensive information about the taxonomic and functional aspects of microbial plant communities, contributing to a better understanding of their dynamics. Evidence of the plant microbiome's functional potential has boosted its exploitation to develop more ecological and sustainable agricultural practices that impact human health. Although microbial inoculants' development and use are promising to revolutionize crop production, interdisciplinary studies are needed to identify new candidates and promote effective practical applications. On the other hand, there are challenges in understanding and analyzing complex data generated within a plant microbiome project's scope. This review presents aspects about the complex structuring and assembly of the microbiome in the host plant's tissues, metagenomics, and metatranscriptomics approaches for its understanding, covering descriptions of recent studies concerning metagenomics to characterize the microbiome of non-model plants under different aspects. Studies involving bio-inoculants, isolated from plant microbial communities, capable of assisting in crops' productivity, are also reviewed.}, }
@article {pmid34668097, year = {2021}, author = {González-Castillo, A and Carballo, JL and Bautista-Guerrero, E}, title = {Genomics and phylogeny of the proposed phylum 'Candidatus Poribacteria' associated with the excavating sponge Thoosa mismalolli.}, journal = {Antonie van Leeuwenhoek}, volume = {114}, number = {12}, pages = {2163-2174}, pmid = {34668097}, issn = {1572-9699}, support = {254806//CONACYT-SEP/ ; }, mesh = {Animals ; *Bacteria/genetics ; Genomics ; Metagenome ; *Microbiota ; Phylogeny ; }, abstract = {Members of the proposed phylum 'Candidatus Poribacteria' are among the most abundant microorganisms in the highly diverse microbiome of the sponge mesohyl. Genomic and phylogenetic characteristics of this proposed phylum are barely known. In this study, we analyzed metagenome-assembled genomes (MAGs) obtained from the coral reef excavating sponge Thoosa mismalolli from the Mexican Pacific Ocean. Two MAGs were extracted and analyzed together with 32 MAGs and single-amplified genomes (SAGs) obtained from NCBI. The phylogenetic tree based on the sequences of 139 single-copy genes (SCG) showed two clades. Clade A (23 genomes) represented 67.7% of the total of the genomes, while clade B (11 genomes) comprised 32.3% of the genomes. The Average Nucleotide Identity (ANI) showed values between 66 and 99% for the genomes of the proposed phylum, and the pangenome of genomes revealed a total of 37,234 genes that included 1722 core gene. The number of genes used in the phylogenetic analysis increased from 28 (previous studies) to 139 (this study), which allowed a better resolution of the phylogeny of the proposed phylum. The results supported the two previously described classes, 'Candidatus Entoporibacteria' and 'Candidatus Pelagiporibacteria', and the genomes SB0101 and SB0202 obtained in this study belong to two new species of the class 'Candidatus Entoporibacteria'. This is the first comparative study that includes MAGs from a non-sponge host (Porites lutea) to elucidate the taxonomy of the poorly known Candidatus phylum in a polyphasic approach. Finally, our study also contributes to the sponge microbiome project by reporting the first MAGs of the proposed phylum 'Candidatus Poribacteria' isolated from the excavating sponge T. mismalolli.}, }
@article {pmid34656848, year = {2021}, author = {Tan-Torres, AL and Brooks, JP and Singh, B and Seashols-Williams, S}, title = {Machine learning clustering and classification of human microbiome source body sites.}, journal = {Forensic science international}, volume = {328}, number = {}, pages = {111008}, doi = {10.1016/j.forsciint.2021.111008}, pmid = {34656848}, issn = {1872-6283}, mesh = {Algorithms ; Cluster Analysis ; Humans ; Machine Learning ; Metagenomics ; *Microbiota ; }, abstract = {Distinct microbial signatures associated with specific human body sites can play a role in the identification of biological materials recovered from the crime scene, but at present, methods that have capability to predict origin of biological materials based on such signatures are limited. Metagenomic sequencing and machine learning (ML) offer a promising enhancement to current identification protocols. We use ML for forensic source body site identification using shotgun metagenomic sequenced data to verify the presence of microbiomic signatures capable of discriminating between source body sites and then show that accurate prediction is possible. The consistency between cluster membership and actual source body site (purity) exceeded 99% at the genus taxonomy using off-the-shelf ML clustering algorithms. Similar results were obtained at the family level. Accurate predictions were observed for genus, family, and order taxonomies, as well as with a core set of 51 genera. The accurate outcomes from our replicable process should encourage forensic scientists to seriously consider integrating ML predictors into their source body site identification protocols.}, }
@article {pmid34611047, year = {2022}, author = {Lv, S and Wang, Y and Zhang, W and Shang, H}, title = {Trimethylamine oxide: a potential target for heart failure therapy.}, journal = {Heart (British Cardiac Society)}, volume = {108}, number = {12}, pages = {917-922}, doi = {10.1136/heartjnl-2021-320054}, pmid = {34611047}, issn = {1468-201X}, mesh = {Cardiotonic Agents ; Carnitine/metabolism ; Choline/metabolism ; Diuretics ; *Gastrointestinal Microbiome/physiology ; *Heart Failure/drug therapy ; Humans ; Methylamines ; }, abstract = {Heart failure (HF) is a clinical syndrome in the late stage of cardiovascular disease and is associated with high prevalence, mortality and rehospitalisation rate. The pathophysiological mechanisms of HF have experienced the initial 'water-sodium retention' mode to 'abnormal hemodynamics' mode, and subsequent to 'abnormal activation of neuroendocrine' mode, which has extensively promoted the reform of HF treatment and updated the treatment concept. Since the Human Microbiome Project commencement, the study on intestinal microecology has swiftly developed, providing a new direction to reveal the occurrence of diseases and the mechanisms behind drug effects. Intestinal microecology comprises the gastrointestinal lumen, epithelial secretion, food entering the intestine, intestinal flora and metabolites. Choline and L-carnitine in the diet are metabolised to trimethylamine (TMA) by the intestinal micro-organisms, with TMA being absorbed into the blood. TMA then enters the liver through the portal vein circulation and is oxidised to trimethylamine oxide (TMAO) by the hepatic flavin-containing mono-oxygenase (FMO) family, especially FMO3. The circulating TMAO levels are associated with adverse outcomes in HF (mortality and readmission), and lower TMAO levels indicate better prognosis. As HF progresses, the concentration of TMAO in patients gradually increases. Whether the circulating TMAO level can be decreased by intervening with the intestinal microflora or relevant enzymes, thereby affecting the prognosis of patients with HF, has become a research hotspot. Therefore, based on the HF intestinal hypothesis, exploring the treatment strategy for HF targeting the TMAO metabolite of the intestinal flora may update the treatment concept in HF and improve its therapeutic effect.}, }
@article {pmid34554215, year = {2022}, author = {Bodein, A and Scott-Boyer, MP and Perin, O and Lê Cao, KA and Droit, A}, title = {timeOmics: an R package for longitudinal multi-omics data integration.}, journal = {Bioinformatics (Oxford, England)}, volume = {38}, number = {2}, pages = {577-579}, doi = {10.1093/bioinformatics/btab664}, pmid = {34554215}, issn = {1367-4811}, support = {//Research and Innovation chair L'Or&#xe9;al in Digital Biology/ ; GNT1159458//National Health and Medical Research Council (NHMRC) Career Development fellowship/ ; }, mesh = {Humans ; *Genomics/methods ; *Multiomics ; Cluster Analysis ; }, abstract = {MOTIVATION: Multi-omics data integration enables the global analysis of biological systems and discovery of new biological insights. Multi-omics experimental designs have been further extended with a longitudinal dimension to study dynamic relationships between molecules. However, methods that integrate longitudinal multi-omics data are still in their infancy.<br><br>RESULTS: We introduce the R package timeOmics, a generic analytical framework for the integration of longitudinal multi-omics data. The framework includes pre-processing, modeling and clustering to identify molecular features strongly associated with time. We illustrate this framework in a case study to detect seasonal patterns of mRNA, metabolites, gut taxa and clinical variables in patients with diabetes mellitus from the integrative Human Microbiome Project.<br><br>timeOmics is available on Bioconductor and github.com/abodein/timeOmics.<br><br>SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.}, }
@article {pmid34530857, year = {2021}, author = {Antonio Paoli, A and Mancin, L and Caprio, M and Monti, E and Narici, MV and Cenci, L and Piccini, F and Pincella, M and Grigoletto, D and Marcolin, G}, title = {Effects of 30 days of ketogenic diet on body composition, muscle strength, muscle area, metabolism, and performance in semi-professional soccer players.}, journal = {Journal of the International Society of Sports Nutrition}, volume = {18}, number = {1}, pages = {62}, pmid = {34530857}, issn = {1550-2783}, mesh = {Adult ; Athletes ; *Body Composition ; *Diet, Ketogenic ; Diet, Western ; Humans ; Male ; *Muscle Strength ; Muscle, Skeletal/*physiology ; Prospective Studies ; *Sports Nutritional Physiological Phenomena ; Young Adult ; }, abstract = {BACKGROUND: A ketogenic diet (KD) is a nutritional approach, usually adopted for weight loss, that restricts daily carbohydrates under 30 g/day. KD showed contradictory results on sport performance, whilst no data are available on team sports. We sought to investigate the influence of a KD on different parameters in semi-professional soccer players.<br><br>METHODS: Subjects were randomly assigned to a iso-protein (1.8&#x2009;g/Kg body weight/day) ketogenic diet (KD) or western diet (WD) for 30&#x2009;days. Body weight and body composition, resting energy expenditure (REE), respiratory exchange ratio (RER), cross sectional area (CSA) and isometric muscle strength of quadriceps, counter movement jump (CMJ) and yoyo intermittent recovery test time were measured.<br><br>RESULTS: There was a significantly higher decrease of body fat (p&#x2009;=&#x2009;0.0359), visceral adipose tissue (VAT) (p&#x2009;=&#x2009;0.0018), waist circumference (p&#x2009;=&#x2009;0.0185) and extra-cellular water (p&#x2009;=&#x2009;0.0060) in KD compared to WD group. Lean soft tissue, quadriceps muscle area, maximal strength and REE showed no changes in both groups. RER decreased significantly in KD (p&#x2009;=&#x2009;0.0008). Yo-yo intermittent test improved significantly (p&#x2009;<&#x2009;0.0001) in both groups without significant differences between groups. CMJ significantly improved (p&#x2009;=&#x2009;0.0021) only in KD.<br><br>CONCLUSIONS: This is the first study investigating the effects of a KD on semi-professional soccer players. In our study KD athletes lost fat mass without any detrimental effects on strength, power and muscle mass. When the goal is a rapid weight reduction in such athletes, the use of a KD should be taken into account.<br><br>TRIAL REGISTRATION: registered retrospectively on Clinical Trial registration number NCT04078971 .}, }
@article {pmid34484688, year = {2021}, author = {Mehta, S and Crane, M and Leith, E and Batut, B and Hiltemann, S and Arntzen, M&#xd8; and Kunath, BJ and Pope, PB and Delogu, F and Sajulga, R and Kumar, P and Johnson, JE and Griffin, TJ and Jagtap, PD}, title = {ASaiM-MT: a validated and optimized ASaiM workflow for metatranscriptomics analysis within Galaxy framework.}, journal = {F1000Research}, volume = {10}, number = {}, pages = {103}, pmid = {34484688}, issn = {2046-1402}, support = {U24 CA199347/CA/NCI NIH HHS/United States ; }, mesh = {High-Throughput Nucleotide Sequencing ; Humans ; Metagenome ; *Metagenomics ; *Microbiota/genetics ; Workflow ; }, abstract = {The Earth Microbiome Project (EMP) aided in understanding the role of microbial communities and the influence of collective genetic material (the 'microbiome') and microbial diversity patterns across the habitats of our planet. With the evolution of new sequencing technologies, researchers can now investigate the microbiome and map its influence on the environment and human health. Advances in bioinformatics methods for next-generation sequencing (NGS) data analysis have helped researchers to gain an in-depth knowledge about the taxonomic and genetic composition of microbial communities. Metagenomic-based methods have been the most commonly used approaches for microbiome analysis; however, it primarily extracts information about taxonomic composition and genetic potential of the microbiome under study, lacking quantification of the gene products (RNA and proteins). On the other hand, metatranscriptomics, the study of a microbial community's RNA expression, can reveal the dynamic gene expression of individual microbial populations and the community as a whole, ultimately providing information about the active pathways in the microbiome. In order to address the analysis of NGS data, the ASaiM analysis framework was previously developed and made available via the Galaxy platform. Although developed for both metagenomics and metatranscriptomics, the original publication demonstrated the use of ASaiM only for metagenomics, while thorough testing for metatranscriptomics data was lacking. In the current study, we have focused on validating and optimizing the tools within ASaiM for metatranscriptomics data. As a result, we deliver a robust workflow that will enable researchers to understand dynamic functional response of the microbiome in a wide variety of metatranscriptomics studies. This improved and optimized ASaiM-metatranscriptomics (ASaiM-MT) workflow is publicly available via the ASaiM framework, documented and supported with training material so that users can interrogate and characterize metatranscriptomic data, as part of larger meta-omic studies of microbiomes.}, }
@article {pmid34485860, year = {2021}, author = {De Boeck, I and Wittouck, S and Martens, K and Spacova, I and Cauwenberghs, E and Allonsius, CN and Jörissen, J and Wuyts, S and Van Beeck, W and Dillen, J and Bron, PA and Steelant, B and Hellings, PW and Vanderveken, OM and Lebeer, S}, title = {The nasal mutualist Dolosigranulum pigrum AMBR11 supports homeostasis via multiple mechanisms.}, journal = {iScience}, volume = {24}, number = {9}, pages = {102978}, pmid = {34485860}, issn = {2589-0042}, abstract = {Comparing the nasal microbiome of healthy individuals and chronic rhinosinusitis (CRS) patients revealed Dolosigranulum pigrum as a species clearly associated with nasal health, although isolates obtained from healthy individuals are scarce. In this study, we explored the properties of this understudied lactic acid bacterium by integrating comparative genomics, habitat mining, cultivation, and functional characterization of interaction capacities. Mining 10.000 samples from the Earth Microbiome Project of 17 habitat types revealed that Dolosigranulum is mainly associated with the human nasal cavity. D. pigrum AMBR11 isolated from the nose of a healthy individual exerted antimicrobial activity against Staphylococcus aureus, decreased proinflammatory cytokine production in airway epithelial cells, and Galleria mellonella larvae mortality induced by this important nasal pathobiont. Furthermore, the strain protected the nasal barrier function in a mouse model using interleukin-4 as disruptive cytokine. Hence, D. pigrum AMBR11 is a mutualist with high potential as topical live biotherapeutic product.}, }
@article {pmid34466295, year = {2021}, author = {Chen, YR and Jing, QL and Chen, FL and Zheng, H and Chen, LD and Yang, ZC}, title = {Desulfovibrio is not always associated with adverse health effects in the Guangdong Gut Microbiome Project.}, journal = {PeerJ}, volume = {9}, number = {}, pages = {e12033}, pmid = {34466295}, issn = {2167-8359}, abstract = {Desulfovibrio (DSV) is frequently found in the human intestine but limited knowledge is available regarding the relationship between DSV and host health. In this study, we analyzed large-scale cohort data from the Guangdong Gut Microbiome Project to study the ecology of DSV and the associations of DSV and host health parameters. Phylogenetic analysis showed that Desulfovibrio piger might be the most common and abundant DSV species in the GGMP. Predominant sub-OTUs of DSV were positively associated with bacterial community diversity. The relative abundance of DSV was positively correlated with beneficial genera, including Oscillospira, Coprococcus,Ruminococcus,Akkermansia, Roseburia,Faecalibacterium, andBacteroides, and was negatively associated with harmful genera, such as Clostridium,Escherichia,Klebsiella, and Ralstonia. Moreover, the relative abundance of DSV was negatively correlated with body mass index, waist size, triglyceride levels, and uric acid levels. This suggests that DSV is associated with healthy hosts in some human populations.}, }
@article {pmid37440868, year = {2021}, author = {Shuler, K and Verbanic, S and Chen, IA and Lee, J}, title = {A Bayesian nonparametric analysis for zero-inflated multivariate count data with application to microbiome study.}, journal = {Journal of the Royal Statistical Society. Series C, Applied statistics}, volume = {70}, number = {4}, pages = {961-979}, pmid = {37440868}, issn = {0035-9254}, support = {DP2 GM123457/GM/NIGMS NIH HHS/United States ; }, abstract = {High-throughput sequencing technology has enabled researchers to profile microbial communities from a variety of environments, but analysis of multivariate taxon count data remains challenging. We develop a Bayesian nonparametric (BNP) regression model with zero inflation to analyse multivariate count data from microbiome studies. A BNP approach flexibly models microbial associations with covariates, such as environmental factors and clinical characteristics. The model produces estimates for probability distributions which relate microbial diversity and differential abundance to covariates, and facilitates community comparisons beyond those provided by simple statistical tests. We compare the model to simpler models and popular alternatives in simulation studies, showing, in addition to these additional community-level insights, it yields superior parameter estimates and model fit in various settings. The model's utility is demonstrated by applying it to a chronic wound microbiome data set and a Human Microbiome Project data set, where it is used to compare microbial communities present in different environments.}, }
@article {pmid34302622, year = {2021}, author = {Hyun, DW and Lee, JY and Kim, MS and Shin, NR and Whon, TW and Kim, KH and Kim, PS and Tak, EJ and Jung, MJ and Lee, JY and Kim, HS and Kang, W and Sung, H and Jeon, CO and Bae, JW}, title = {Pathogenomics of Streptococcus ilei sp. nov., a newly identified pathogen ubiquitous in human microbiome.}, journal = {Journal of microbiology (Seoul, Korea)}, volume = {59}, number = {8}, pages = {792-806}, pmid = {34302622}, issn = {1976-3794}, mesh = {Adult ; Animals ; Gastrointestinal Microbiome ; Humans ; Ileostomy ; Male ; Mice ; Mice, Inbred C57BL ; *Microbiota ; Phylogeny ; Streptococcal Infections/*microbiology ; Streptococcus/classification/genetics/*isolation &amp; purification/*pathogenicity ; Virulence ; }, abstract = {Viridans group streptococci are a serious health concern because most of these bacteria cause life-threatening infections, especially in immunocompromised and hospitalized individuals. We focused on two alpha-hemolytic Streptococcus strains (I-G2 and I-P16) newly isolated from an ileostomy effluent of a colorectal cancer patient. We examined their pathogenic potential by investigating their prevalence in human and assessing their pathogenicity in a mouse model. We also predicted their virulence factors and pathogenic features by using comparative genomic analysis and in vitro tests. Using polyphasic and systematic approaches, we identified the isolates as belonging to a novel Streptococcus species and designated it as Streptococcus ilei. Metagenomic survey based on taxonomic assignment of datasets from the Human Microbiome Project revealed that S. ilei is present in most human population and at various body sites but is especially abundant in the oral cavity. Intraperitoneal injection of S. ilei was lethal to otherwise healthy C57BL/6J mice. Pathogenomics and in vitro assays revealed that S. ilei possesses a unique set of virulence factors. In agreement with the in vivo and in vitro data, which indicated that S. ilei strain I-G2 is more pathogenic than strain I-P16, only the former displayed the streptococcal group A antigen. We here newly identified S. ilei sp. nov., and described its prevalence in human, virulence factors, and pathogenicity. This will help to prevent S. ilei strain misidentification in the future, and improve the understanding and management of streptococcal infections.}, }
@article {pmid34259548, year = {2021}, author = {Wang, J and Wang, J and Wu, S and Zhang, Z and Li, Y}, title = {Global Geographic Diversity and Distribution of the Myxobacteria.}, journal = {Microbiology spectrum}, volume = {9}, number = {1}, pages = {e0001221}, pmid = {34259548}, issn = {2165-0497}, mesh = {*Biodiversity ; Environmental Microbiology ; Myxococcales/*classification/genetics/*isolation &amp; purification ; Phylogeny ; Soil/chemistry ; Soil Microbiology ; }, abstract = {Bacteria are globally distributed in various environments on earth, but a global view of the geographic diversity and distribution of a single taxon is lacking. The Earth Microbiome Project (EMP) has established a global collection of microbial communities, providing the possibility for such a survey. Myxococcales is a bacterial order with a potent ability to produce diverse natural products and have wide application potential in agriculture, biomedicine, and environmental protection. In this study, through a comparative analysis of the EMP data and public information, we determined that myxobacteria account for 2.34% of the total bacterial operational taxonomic units (OTUs), and are one of the most diverse bacterial groups on Earth. Myxococcales OTUs are globally distributed and prefer nonsaline soil and sediments, followed by saline environments, but rarely appear in host-associated environments. Myxobacteria are among the least-investigated bacterial groups. The presently cultured and genome-sequenced myxobacteria are most likely environmentally widespread and abundant taxa, and account for approximately 10% and 7% of the myxobacterial community (>97% similarity), respectively. This global panoramic view of the geographic distribution and diversity of myxobacteria, as well as their cultured and genome-sequenced information, will enable us to explore these important bioresources more reasonably and efficiently. The diversity and distribution of myxobacteria beyond the EMP data are further discussed. IMPORTANCE The diversity and distribution of bacteria are crucial for our understanding of their ecological importance and application potential. Myxobacteria are fascinating prokaryotes with multicellular behaviors and a potent capacity for producing secondary metabolites, and have a wide range of potential applications. The ecological importance of myxobacteria in major ecosystems is becoming established, but the global geographic diversity and distribution remain unclear. From a global survey we revealed that Myxococcales OTUs are globally distributed and prefer nonsaline soil and sediments, followed by saline environments, but rarely appear in host-associated environments. The global panoramic view of the geographic distribution and diversity of myxobacteria, as well as their cultured and genome-sequenced information, will enable us to explore these important bioresources more reasonably and efficiently.}, }
@article {pmid34222331, year = {2021}, author = {DiMucci, D and Kon, M and Segrè, D}, title = {BowSaw: Inferring Higher-Order Trait Interactions Associated With Complex Biological Phenotypes.}, journal = {Frontiers in molecular biosciences}, volume = {8}, number = {}, pages = {663532}, pmid = {34222331}, issn = {2296-889X}, abstract = {Machine learning is helping the interpretation of biological complexity by enabling the inference and classification of cellular, organismal and ecological phenotypes based on large datasets, e.g., from genomic, transcriptomic and metagenomic analyses. A number of available algorithms can help search these datasets to uncover patterns associated with specific traits, including disease-related attributes. While, in many instances, treating an algorithm as a black box is sufficient, it is interesting to pursue an enhanced understanding of how system variables end up contributing to a specific output, as an avenue toward new mechanistic insight. Here we address this challenge through a suite of algorithms, named BowSaw, which takes advantage of the structure of a trained random forest algorithm to identify combinations of variables ("rules") frequently used for classification. We first apply BowSaw to a simulated dataset and show that the algorithm can accurately recover the sets of variables used to generate the phenotypes through complex Boolean rules, even under challenging noise levels. We next apply our method to data from the integrative Human Microbiome Project and find previously unreported high-order combinations of microbial taxa putatively associated with Crohn's disease. By leveraging the structure of trees within a random forest, BowSaw provides a new way of using decision trees to generate testable biological hypotheses.}, }
@article {pmid32742640, year = {2020}, author = {Wagner, J and Kancherla, J and Braccia, D and Matsumara, J and Felix, V and Crabtree, J and Mahurkar, A and Corrada Bravo, H}, title = {Interactive exploratory data analysis of Integrative Human Microbiome Project data using Metaviz.}, journal = {F1000Research}, volume = {9}, number = {}, pages = {601}, pmid = {32742640}, issn = {2046-1402}, support = {R01 GM114267/GM/NIGMS NIH HHS/United States ; U54 DK102556/DK/NIDDK NIH HHS/United States ; }, mesh = {*Data Analysis ; Data Interpretation, Statistical ; Humans ; *Microbiota ; Research Design ; }, abstract = {The rich data produced by the second phase of the Human Microbiome Project (iHMP) offers a unique opportunity to test hypotheses that interactions between microbial communities and a human host might impact an individual's health or disease status. In this work we describe infrastructure that integrates Metaviz, an interactive microbiome data analysis and visualization tool, with the iHMP Data Coordination Center web portal and the HMP2Data R/Bioconductor package. We describe integrative statistical and visual analyses of two datasets from iHMP using Metaviz along with the metagenomeSeq R/Bioconductor package for statistical analysis of differential abundance analysis. These use cases demonstrate the utility of a combined approach to access and analyze data from this resource.}, }
@article {pmid34108237, year = {2022}, author = {Le Roy, T and Moens de Hase, E and Van Hul, M and Paquot, A and Pelicaen, R and Régnier, M and Depommier, C and Druart, C and Everard, A and Maiter, D and Delzenne, NM and Bindels, LB and de Barsy, M and Loumaye, A and Hermans, MP and Thissen, JP and Vieira-Silva, S and Falony, G and Raes, J and Muccioli, GG and Cani, PD}, title = {Dysosmobacter welbionis is a newly isolated human commensal bacterium preventing diet-induced obesity and metabolic disorders in mice.}, journal = {Gut}, volume = {71}, number = {3}, pages = {534-543}, pmid = {34108237}, issn = {1468-3288}, mesh = {Animals ; Case-Control Studies ; Clostridiales/*isolation &amp; purification ; Cohort Studies ; Humans ; Insulin Resistance ; Metabolic Diseases/*microbiology/*prevention &amp; control ; Mice ; Mice, Obese ; Obesity/*microbiology/*prevention &amp; control ; }, abstract = {OBJECTIVE: To investigate the abundance and the prevalence of Dysosmobacter welbionis J115[T], a novel butyrate-producing bacterium isolated from the human gut both in the general population and in subjects with metabolic syndrome. To study the impact of this bacterium on host metabolism using diet-induced obese and diabetic mice.<br><br>DESIGN: We analysed the presence and abundance of the bacterium in 11&#x2009;984 subjects using four human cohorts (ie, Human Microbiome Project, American Gut Project, Flemish Gut Flora Project and Microbes4U). Then, we tested the effects of daily oral gavages with live D. welbionis J115[T] on metabolism and several hallmarks of obesity, diabetes, inflammation and lipid metabolism in obese/diabetic mice.<br><br>RESULTS: This newly identified bacterium was detected in 62.7%-69.8% of the healthy population. Strikingly, in obese humans with a metabolic syndrome, the abundance of Dysosmobacter genus correlates negatively with body mass index, fasting glucose and glycated haemoglobin. In mice, supplementation with live D. welbionis J115[T], but not with the pasteurised bacteria, partially counteracted diet-induced obesity development, fat mass gain, insulin resistance and white adipose tissue hypertrophy and inflammation. In addition, live D. welbionis J115[T] administration protected the mice from brown adipose tissue inflammation in association with increased mitochondria number and non-shivering thermogenesis. These effects occurred with minor impact on the mouse intestinal microbiota composition.<br><br>CONCLUSIONS: These results suggest that D. welbionis J115[T] directly and beneficially influences host metabolism and is a strong candidate for the development of next-generation beneficial bacteria targeting obesity and associated metabolic diseases.}, }
@article {pmid34084131, year = {2021}, author = {Hollingsworth, BA and Cassatt, DR and DiCarlo, AL and Rios, CI and Satyamitra, MM and Winters, TA and Taliaferro, LP}, title = {Acute Radiation Syndrome and the Microbiome: Impact and Review.}, journal = {Frontiers in pharmacology}, volume = {12}, number = {}, pages = {643283}, pmid = {34084131}, issn = {1663-9812}, abstract = {Study of the human microbiota has been a centuries-long endeavor, but since the inception of the National Institutes of Health (NIH) Human Microbiome Project in 2007, research has greatly expanded, including the space involving radiation injury. As acute radiation syndrome (ARS) is multisystemic, the microbiome niches across all areas of the body may be affected. This review highlights advances in radiation research examining the effect of irradiation on the microbiome and its potential use as a target for medical countermeasures or biodosimetry approaches, or as a medical countermeasure itself. The authors also address animal model considerations for designing studies, and the potential to use the microbiome as a biomarker to assess radiation exposure and predict outcome. Recent research has shown that the microbiome holds enormous potential for mitigation of radiation injury, in the context of both radiotherapy and radiological/nuclear public health emergencies. Gaps still exist, but the field is moving forward with much promise.}, }
@article {pmid34040632, year = {2021}, author = {Andreu-Sánchez, S and Chen, L and Wang, D and Augustijn, HE and Zhernakova, A and Fu, J}, title = {A Benchmark of Genetic Variant Calling Pipelines Using Metagenomic Short-Read Sequencing.}, journal = {Frontiers in genetics}, volume = {12}, number = {}, pages = {648229}, pmid = {34040632}, issn = {1664-8021}, abstract = {Microbes live in complex communities that are of major importance for environmental ecology, public health, and animal physiology and pathology. Short-read metagenomic shotgun sequencing is currently the state-of-the-art technique for exploring these communities. With the aid of metagenomics, our understanding of the microbiome is moving from composition toward functionality, even down to the genetic variant level. While the exploration of single-nucleotide variation in a genome is a standard procedure in genomics, and many sophisticated tools exist to perform this task, identification of genetic variation in metagenomes remains challenging. Major factors that hamper the widespread application of variant-calling analysis include low-depth sequencing of individual genomes (which is especially significant for the microorganisms present in low abundance), the existence of large genomic variation even within the same species, the absence of comprehensive reference genomes, and the noise introduced by next-generation sequencing errors. Some bioinformatics tools, such as metaSNV or InStrain, have been created to identify genetic variants in metagenomes, but the performance of these tools has not been systematically assessed or compared with the variant callers commonly used on single or pooled genomes. In this study, we benchmark seven bioinformatic tools for genetic variant calling in metagenomics data and assess their performance. To do so, we simulated metagenomic reads to mimic human microbial composition, sequencing errors, and genetic variability. We also simulated different conditions, including low and high depth of coverage and unique or multiple strains per species. Our analysis of the simulated data shows that probabilistic method-based tools such as HaplotypeCaller and Mutect2 from the GATK toolset show the best performance. By applying these tools to longitudinal gut microbiome data from the Human Microbiome Project, we show that the genetic similarity between longitudinal samples from the same individuals is significantly greater than the similarity between samples from different individuals. Our benchmark shows that probabilistic tools can be used to call metagenomes, and we recommend the use of GATK's tools as reliable variant callers for metagenomic samples.}, }
@article {pmid34040404, year = {2021}, author = {Zhou, Q and Pang, G and Zhang, Z and Yuan, H and Chen, C and Zhang, N and Yang, Z and Sun, L}, title = {Association Between Gut Akkermansia and Metabolic Syndrome is Dose-Dependent and Affected by Microbial Interactions: A Cross-Sectional Study.}, journal = {Diabetes, metabolic syndrome and obesity : targets and therapy}, volume = {14}, number = {}, pages = {2177-2188}, pmid = {34040404}, issn = {1178-7007}, abstract = {OBJECTIVE: Akkermansia muciniphila is among the most abundant bacterial species in the human intestine; however, its relationship to metabolic syndrome (MetS)-which is linked to gut dysbiosis-is not known. In this study, we investigated the association between Akkermansia abundance and risk of MetS and its components, as well as dose-response effects and the influence of microbial interactions on the association.<br><br>METHODS: This cross-sectional study included 6896 Chinese participants aged 18 to 97 years from the Guangdong Gut Microbiome Project. MetS was defined according to Joint Committee for Developing Chinese Guidelines on Prevention and Treatment of Dyslipidemia in Adults criteria. The abundance of Akkermansia was assessed by 16S rRNA sequencing. Logistic regression analysis with adjustment for common confounders was performed to evaluate the association between Akkermansia and MetS and its components. Models with restricted cubic splines and interaction terms were used to examine the dose-response association and microbial interactions, respectively.<br><br>RESULTS: The prevalence of MetS was 20.4%, and the median abundance of Akkermansia was 0.08% (interquartile range: 0.04-0.93%). Increased Akkermansia abundance was associated with decreased risk of MetS (P nonlinear<0.05), but this effect was not observed until the Akkermansia level was 0.2% of the total gut microbiota abundance (odds ratio=0.96, 95% confidence interval: 0.94-0.98). Of the 5 MetS components, obesity and hypertriglyceridemia showed the strongest association with Akkermansia, followed by reduced high-density lipoprotein cholesterol, hypertension, and hyperglycemia. Microbial interaction analyses showed that Ruminococcaceae and Lachnospiraceae were the predominant bacterial families and were not only correlated with Akkermansia abundance but also influenced the Akkermansia-MetS association.<br><br>CONCLUSION: There is a dose-response association between reduced risk of MetS and increased abundance of Akkermansia. The association between Akkermansia and 5 MetS components is variable and affected by microbial interactions.}, }
@article {pmid34026361, year = {2021}, author = {Rogers, AE and Hu, YJ and Yue, Y and Wissel, EF and Petit Iii, RA and Jarrett, S and Christie, J and Read, TD}, title = {Shiftwork, functional bowel symptoms, and the microbiome.}, journal = {PeerJ}, volume = {9}, number = {}, pages = {e11406}, pmid = {34026361}, issn = {2167-8359}, support = {R01 GM116065/GM/NIGMS NIH HHS/United States ; }, abstract = {BACKGROUND: There are about 15 million Americans working full-time on evening, night, or rotating shifts. Between 48% and 81.9% of those working rotating or night shifts report abdominal pain, constipation, diarrhea and other symptoms of functional bowel disorders. The basis for this high prevalence of functional bowel disorders, including irritable bowel syndrome (IBS), among shift workers is unknown. Animal studies, however, suggest that circadian disruption, similar to that in shift workers, may contribute to the development of GI complaints among shift workers by altering the composition and normal diurnal rhythmicity of the resident intestinal microbes. Therefore, the present study was designed to determine if there were differences in (1) composition and diversity of the microbiome of night shift workers compared to day shift workers; and (2) the composition and diversity of the microbiome among shift workers experiencing functional bowel symptoms compared to shift workers who did not experience functional bowel symptoms.<br><br>METHODS: Fifty-one full time staff nurses who worked either 12-hour day or night shifts completed demographic information, and the Rome III IBS module. They also collected two samples of gut microbiota before the beginning and at the end of their last work shift on day 14, using validated field-tested methods consistent with the Human Microbiome Project. After DNA extraction, 16S rRNA sequencing and assignment to the genus level was completed, samples were then compared to determine if there were (1) differences in the diversity and profile of the microbiome by shift type; (2) if there were differences in the microbiome by time of day for collection; and (3) whether there were differences in the diversity and profile of the microbiome of nurses with IBS and those without IBS.<br><br>RESULTS: There were no differences in alpha or beta diversity of gut microbiota when specimens from day and night shift nurses were compared. There were however marginal differences in beta diversity when specimens collected at the beginning and end of the shifts were compared, with seven OTUs being differentially abundant when collected from day shift workers in the evening. There were also three OTUs to be differentially abundant in participants reporting IBS symptoms.}, }
@article {pmid34020714, year = {2021}, author = {Liu, C and Du, MX and Abuduaini, R and Yu, HY and Li, DH and Wang, YJ and Zhou, N and Jiang, MZ and Niu, PX and Han, SS and Chen, HH and Shi, WY and Wu, L and Xin, YH and Ma, J and Zhou, Y and Jiang, CY and Liu, HW and Liu, SJ}, title = {Enlightening the taxonomy darkness of human gut microbiomes with a cultured biobank.}, journal = {Microbiome}, volume = {9}, number = {1}, pages = {119}, pmid = {34020714}, issn = {2049-2618}, mesh = {Bacteria/genetics ; Biological Specimen Banks ; Darkness ; *Gastrointestinal Microbiome/genetics ; Humans ; *Microbiota/genetics ; RNA, Ribosomal, 16S/genetics ; }, abstract = {BACKGROUND: In gut microbiome studies, the cultured gut microbial resource plays essential roles, such as helping to unravel gut microbial functions and host-microbe interactions. Although several major studies have been performed to elucidate the cultured human gut microbiota, up to 70% of the Unified Human Gastrointestinal Genome species have not been cultured to date. Large-scale gut microbial isolation and identification as well as availability to the public are imperative for gut microbial studies and further characterizing human gut microbial functions.<br><br>RESULTS: In this study, we constructed a human Gut Microbial Biobank (hGMB; homepage: hgmb.nmdc.cn) through the cultivation of 10,558 isolates from 31 sample mixtures of 239 fresh fecal samples from healthy Chinese volunteers, and deposited 1170 strains representing 400 different species in culture collections of the International Depository Authority for long-term preservation and public access worldwide. Following the rules of the International Code of Nomenclature of Prokaryotes, 102 new species were characterized and denominated, while 28 new genera and 3 new families were proposed. hGMB represented over 80% of the common and dominant human gut microbial genera and species characterized from global human gut 16S rRNA gene amplicon data (n = 11,647) and cultured 24 "most-wanted" and "medium priority" taxa proposed by the Human Microbiome Project. We in total sequenced 115 genomes representing 102 novel taxa and 13 previously known species. Further in silico analysis revealed that the newly sequenced hGMB genomes represented 22 previously uncultured species in the Unified Human Gastrointestinal Genome (UHGG) and contributed 24 representatives of potentially "dark taxa" that had not been discovered by UHGG. The nonredundant gene catalogs generated from the hGMB genomes covered over 50% of the functionally known genes (KEGG orthologs) in the largest global human gut gene catalogs and approximately 10% of the "most wanted" functionally unknown proteins in the FUnkFams database.<br><br>CONCLUSIONS: A publicly accessible human Gut Microbial Biobank (hGMB) was established that contained 1170 strains and represents 400 human gut microbial species. hGMB expands the gut microbial resources and genomic repository by adding 102 novel species, 28 new genera, 3 new families, and 115 new genomes of human gut microbes. Video abstract.}, }
@article {pmid33998042, year = {2021}, author = {Herzig, AF and Velo-Suárez, L and Le Folgoc, G and Boland, A and Blanché, H and Olaso, R and Le Roux, L and Delmas, C and Goldberg, M and Zins, M and Lethimonnier, F and Deleuze, JF and Génin, E}, title = {Evaluation of saliva as a source of accurate whole-genome and microbiome sequencing data.}, journal = {Genetic epidemiology}, volume = {45}, number = {5}, pages = {537-548}, doi = {10.1002/gepi.22386}, pmid = {33998042}, issn = {1098-2272}, mesh = {Genome, Human ; Genotype ; Humans ; *Microbiota/genetics ; *Saliva ; Whole Genome Sequencing ; }, abstract = {This study sets out to establish the suitability of saliva-based whole-genome sequencing (WGS) through a comparison against blood-based WGS. To fully appraise the observed differences, we developed a novel technique of pseudo-replication. We also investigated the potential of characterizing individual salivary microbiomes from non-human DNA fragments found in saliva. We observed that the majority of discordant genotype calls between blood and saliva fell into known regions of the human genome that are typically sequenced with low confidence; and could be identified by quality control measures. Pseudo-replication demonstrated that the levels of discordance between blood- and saliva-derived WGS data were entirely similar to what one would expect between technical replicates if an individual's blood or saliva had been sequenced twice. Finally, we successfully sequenced salivary microbiomes in parallel to human genomes as demonstrated by a comparison against the Human Microbiome Project.}, }
@article {pmid39296320, year = {2021}, author = {Brostow, DP and Stamper, CE and Stanislawski, MA and Stearns-Yoder, KA and Schneider, A and Postolache, TT and Forster, JE and Hoisington, AJ and Lowry, CA and Brenner, LA}, title = {Dietary habits and the gut microbiota in military Veterans: results from the United States-Veteran Microbiome Project (US-VMP).}, journal = {Gut microbiome (Cambridge, England)}, volume = {2}, number = {}, pages = {e1}, pmid = {39296320}, issn = {2632-2897}, abstract = {Dietary patterns influence gut microbiota composition. To date, there has not been an assessment of diet and gut microbiota in Veterans, who have a history of unique environmental exposures, including military deployment, that may influence associations between diet and gut microbiota. Our aim was to characterise Veteran habitual dietary intake and quality, and to evaluate correlations between diet and gut microbiota. We administered Food Frequency Questionnaires (FFQs) and collected stool samples from 330 Veterans. FFQ data were used to generate Healthy Eating Indices (HEI) of dietary quality. Exploratory factor analysis was used to identify two dietary patterns we defined as "Western" and "Prudent." Stool samples underwent 16S rRNA gene sequencing, and the resulting data were used to evaluate associations with dietary variables/indices. Analyses included linear regression of α-diversity, constrained analysis of principal coordinates of β-diversity, and multivariate association with linear models and Analysis of Composition of Microbiomes analyses of dietary factors and phylum- and genus-level taxa. There were no significant associations between dietary patterns or factors and α- or β-diversity. At the phylum level, increasing HEI scores were inversely associated with relative abundance of Actinobacteria, and added sugar was inversely associated with abundance of Verrucomicrobia. Veterans largely consumed a Western-style diet, characterised by poor adherence to nutritional guidelines.}, }
@article {pmid33888782, year = {2021}, author = {Pinto, D and Ciardiello, T and Franzoni, M and Pasini, F and Giuliani, G and Rinaldi, F}, title = {Effect of commonly used cosmetic preservatives on skin resident microflora dynamics.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {8695}, pmid = {33888782}, issn = {2045-2322}, mesh = {Cosmetics/*chemistry ; Histone Deacetylases/metabolism ; Humans ; Microbiota/*drug effects ; Preservatives, Pharmaceutical/*pharmacology ; Propionibacterium acnes/drug effects ; Skin/enzymology/*microbiology ; Staphylococcus aureus/drug effects ; Staphylococcus epidermidis/drug effects ; }, abstract = {Human skin is populated by various microorganisms, the so-called microbiota, such as bacteria, viruses, yeasts, fungi, and archaea. The skin microbiota is in constant contact with the surrounding environment which can alter its eubiotic state. Recently it has been also observed that the application of cosmetic products can alter the balance of the skin microbiota. This effect may be attributed to many factors including the residual activity of the preservatives on the skin. In the present work, we studied the effect of eleven preservatives commonly found in cosmetic products on Propionibacterium acnes, Staphylococcus epidermidis, and Staphylococcus aureus in vitro using 3D skin models and culture-dependent methods. Also, the effect on Histone deacetylase 3 (HDAC3) has been investigated. Among tested combinations, three resulted as the best suitable for restoring a pre-existing dysbiosis since they act moderately inhibiting C. acnes and strongly S. aureus without simultaneously inhibiting the growth of S. epidermidis. The other four combinations resulted as the best suitable for use in topical products for skin and scalp in which it is necessary to preserve the eubiosis of the microbiota. Some of the tested were also able to increase HDAC3 expression. Taking together these data highlight the role of preservatives of skin resident microflora dynamics and could provide a reference for correctly choice preservatives and dosage in cosmetic formulations to preserve or restore homeostasis of skin microbiota.}, }
@article {pmid33796485, year = {2021}, author = {Ceprnja, M and Oros, D and Melvan, E and Svetlicic, E and Skrlin, J and Barisic, K and Starcevic, L and Zucko, J and Starcevic, A}, title = {Modeling of Urinary Microbiota Associated With Cystitis.}, journal = {Frontiers in cellular and infection microbiology}, volume = {11}, number = {}, pages = {643638}, pmid = {33796485}, issn = {2235-2988}, mesh = {*Cystitis ; Dysbiosis ; Female ; Humans ; *Microbiota ; *Urinary Tract Infections ; }, abstract = {A decade ago, when the Human Microbiome Project was starting, urinary tract (UT) was not included because the bladder and urine were considered to be sterile. Today, we are presented with evidence that healthy UT possesses native microbiota and any major event disrupting its "equilibrium" can impact the host also. This dysbiosis often leads to cystitis symptoms, which is the most frequent lower UT complaint, especially among women. Cystitis is one of the most common causes of antimicrobial drugs prescriptions in primary and secondary care and an important contributor to the problem of antimicrobial resistance. Despite this fact, we still have trouble distinguishing whether the primary cause of majority of cystitis cases is a single pathogen overgrowth, or a systemic disorder affecting entire UT microbiota. There are relatively few studies monitoring changes and dynamics of UT microbiota in cystitis patients, making this field of research still an unknown. In this study variations to the UT microbiota of cystitis patients were identified and microbial dynamics has been modeled. The microbial genetic profile of urine samples from 28 patients was analyzed by 16S rDNA Illumina sequencing and bioinformatics analysis. One patient with bacterial cystitis symptoms was prescribed therapy based on national guideline recommendations on antibacterial treatment of urinary tract infections (UTI) and UT microbiota change was monitored by 16S rDNA sequencing on 24 h basis during the entire therapy duration. The results of sequencing implied that a particular class of bacteria is associated with majority of cystitis cases in this study. The contributing role of this class of bacteria - Gammaproteobacteria, was further predicted by generalized Lotka-Volterra modeling (gLVM). Longitudinal microbiota insight obtained from a single patient under prescribed antimicrobial therapy revealed rapid and extensive changes in microbial composition and emphasized the need for current guidelines revision in regards to therapy duration. Models based on gLVM indicated protective role of two taxonomic classes of bacteria, Actinobacteria and Bacteroidia class, which appear to actively suppress pathogen overgrowth.}, }
@article {pmid33738265, year = {2021}, author = {Ma, Y and Zhang, Y and Xiang, J and Xiang, S and Zhao, Y and Xiao, M and Du, F and Ji, H and Kaboli, PJ and Wu, X and Li, M and Wen, Q and Shen, J and Yang, Z and Li, J and Xiao, Z}, title = {Metagenome Analysis of Intestinal Bacteria in Healthy People, Patients With Inflammatory Bowel Disease and Colorectal Cancer.}, journal = {Frontiers in cellular and infection microbiology}, volume = {11}, number = {}, pages = {599734}, pmid = {33738265}, issn = {2235-2988}, mesh = {Bacteria/genetics ; *Colorectal Neoplasms ; Humans ; *Inflammatory Bowel Diseases ; Metagenome ; Metagenomics ; RNA, Ribosomal, 16S/genetics ; }, abstract = {OBJECTIVES: Several reports suggesting that the intestinal microbiome plays a key role in the development of inflammatory bowel disease (IBD) or colorectal cancer (CRC), but the changes of intestinal bacteria in healthy people, patients with IBD and CRC are not fully explained. The study aimed to investigate changes of intestinal bacteria in healthy subjects, patients with IBD, and patients with CRC.<br><br>MATERIALS: We collected data from the European Nucleotide Archive on healthy people and patients with colorectal cancer with the study accession number PRJEB6070, PRJEB7774, PRJEB27928, PRJEB12449, and PRJEB10878, collected IBD patient data from the Integrated Human Microbiome Project from the Human Microbiome Project Data Portal. We performed metagenome-wide association studies on the fecal samples from 290 healthy subjects, 512 IBD patients, and 285 CRC patients. We used the metagenomics dataset to study bacterial community structure, relative abundance, functional prediction, differentially abundant bacteria, and co-occurrence networks.<br><br>RESULTS: The bacterial community structure in both IBD and CRC was significantly different from healthy subjects. Our results showed that IBD patients had low intestinal bacterial diversity and CRC patients had high intestinal bacterial diversity compared to healthy subjects. At the phylum level, the relative abundance of Firmicutes in IBD decreased significantly, while the relative abundance of Bacteroidetes increased significantly. At the genus level, the relative abundance of Bacteroides in IBD was higher than in healthy people and CRC. Compared with healthy people and CRC, the main difference of intestinal bacteria in IBD patients was Bacteroidetes, and compared with healthy people and IBD, the main difference of intestinal bacteria in CRC patients was in Fusobacteria, Verrucomicrobia, and Proteobacteria. The main differences in the functional composition of intestinal bacteria in healthy people, IBD and CRC patients were L-homoserine and L-methionine biosynthesis, 5-aminoimidazole ribonucleotide biosynthesis II, L-methionine biosynthesis I, and superpathway of L-lysine, L-threonine, and L-methionine biosynthesis I. The results of stratified showed that the abundance of Firmicutes, Bacteroidetes, and Actinobacteria involved in metabolic pathways has significantly changed. Besides, the association network of intestinal bacteria in healthy people, IBD, and CRC patients has also changed.<br><br>CONCLUSIONS: In conclusion, compared with healthy people, the taxonomic and functional composition of intestinal bacteria in IBD and CRC patients was significantly changed.}, }
@article {pmid33718417, year = {2021}, author = {Zhou, Y and He, Y and Liu, L and Zhou, W and Wang, P and Hu, H and Nie, Y and Chen, Y}, title = {Alterations in Gut Microbial Communities Across Anatomical Locations in Inflammatory Bowel Diseases.}, journal = {Frontiers in nutrition}, volume = {8}, number = {}, pages = {615064}, pmid = {33718417}, issn = {2296-861X}, abstract = {We previously discovered that gut microbiota can serve as universal microbial biomarkers for diagnosis, disease activity assessment, and predicting the response to infliximab treatment for inflammatory bowel diseases (IBD). Much still remains unknown about the relationship between alterations in gut microbiota and IBD affected bowel region, in particular in the case of ulcerative colitis (UC) and colonic Crohn's disease (cCD) without endoscopic and biopsy data. In the current study gut microbiota from a population in China was found to be distinct from that of the Western world [Human Microbiome Project (HMP) data]. Furthermore, both gut microbiota greatly differed from microbiota of other anatomical locations (oral, skin, airway, and vagina), with higher alpha-diversity (Chinese gut > HMP gut > oral microbiome > airway microbiome > skin microbiome > vaginal microbiome), and marked differences in microbiome composition. In patients with IBD in China, UC was characterized by the presence of Gardnerella, while cCD was characterized by the presence of Fusobacterium. Moreover, gut microbiota, such as Gardnerella and Fusobacterium, may be potential biomarkers for identifying UC from cCD. Together, this study revealed crucial differences in microbial communities across anatomical locations, and demonstrated that there was an important association between IBD affected bowel region and gut microbiota.}, }
@article {pmid33682945, year = {2021}, author = {Bar, J and Sarig, O and Lotan-Pompan, M and Dassa, B and Miodovnik, M and Weinberger, A and Sprecher, E and Segal, E and Samuelov, L}, title = {Evidence for cutaneous dysbiosis in dystrophic epidermolysis bullosa.}, journal = {Clinical and experimental dermatology}, volume = {46}, number = {7}, pages = {1223-1229}, doi = {10.1111/ced.14592}, pmid = {33682945}, issn = {1365-2230}, support = {//EB Research Partnership foundation/ ; }, mesh = {Adolescent ; Adult ; Bacteria/*isolation &amp; purification ; Case-Control Studies ; Child, Preschool ; Dysbiosis/*complications ; Epidermolysis Bullosa Dystrophica/complications/genetics/*microbiology ; Genotype ; Humans ; *Microbiota ; Skin/*microbiology ; Staphylococcus/isolation &amp; purification ; Young Adult ; }, abstract = {BACKGROUND: The human microbiome project addresses the relationship between bacterial flora and the human host, in both healthy and diseased conditions. The skin is an ecosystem with multiple niches, each featuring unique physiological conditions and thus hosting different bacterial populations. The skin microbiome has been implicated in the pathogenesis of many dermatoses. Given the role of dysbiosis in the pathogenesis of inflammation, which is prominent in dystrophic epidermolysis bullosa (DEB), we undertook a study on the skin microbiome.<br><br>AIM: To characterize the skin microbiome in a series of patients with DEB.<br><br>METHODS: This was a case-control study of eight patients with DEB and nine control cases enrolled between June 2017 and November 2018. The skin of patients with DEB was sampled at three different sites: untreated wound, perilesional skin and normal-appearing (uninvolved) skin. Normal skin on the forearm was sampled from age-matched healthy controls (HCs). We used a dedicated DNA extraction protocol to isolate microbial DNA, which was then analysed using next-generation microbial 16S rRNA sequencing. Data were analysed using a series of advanced bioinformatics tools.<br><br>RESULTS: The wounds, perilesional and uninvolved skin of patients with DEB demonstrated reduced bacterial diversity compared with HCs, with the flora in DEB wounds being the least diverse. We found an increased prevalence of staphylococci species in the lesional and perilesional skin of patients with DEB, compared with their uninvolved, intact skin. Similarly, the uninvolved skin of patients with DEB displayed increased staphylococcal content and significantly different microbiome diversities (other than staphylococci) compared with HC skin.<br><br>CONCLUSIONS: These findings suggest the existence of a unique DEB-associated skin microbiome signature, which could be targeted by specific pathogen-directed therapies. Moreover, altering the skin microbiome with increasing colonization of bacteria associated with nonchronic wounds may potentially facilitate wound healing in patients with DEB.}, }
@article {pmid33674782, year = {2021}, author = {Nuzzo, A and Saha, S and Berg, E and Jayawickreme, C and Tocker, J and Brown, JR}, title = {Expanding the drug discovery space with predicted metabolite-target interactions.}, journal = {Communications biology}, volume = {4}, number = {1}, pages = {288}, pmid = {33674782}, issn = {2399-3642}, mesh = {Anti-Inflammatory Agents/*pharmacology ; Bacteria/immunology/*metabolism ; Cells, Cultured ; Data Mining ; Databases, Factual ; *Drug Discovery ; Gastrointestinal Agents/*pharmacology ; *Gastrointestinal Microbiome ; Gene Expression Profiling ; Host-Pathogen Interactions ; Humans ; Inflammatory Bowel Diseases/*drug therapy/immunology/metabolism/microbiology ; Ligands ; *Machine Learning ; Metabolome ; Metabolomics ; Molecular Targeted Therapy ; *Protein Interaction Maps ; Signal Transduction ; Transcriptome ; }, abstract = {Metabolites produced in the human gut are known modulators of host immunity. However, large-scale identification of metabolite-host receptor interactions remains a daunting challenge. Here, we employed computational approaches to identify 983 potential metabolite-target interactions using the Inflammatory Bowel Disease (IBD) cohort dataset of the Human Microbiome Project 2 (HMP2). Using a consensus of multiple machine learning methods, we ranked metabolites based on importance to IBD, followed by virtual ligand-based screening to identify possible human targets and adding evidence from compound assay, differential gene expression, pathway enrichment, and genome-wide association studies. We confirmed known metabolite-target pairs such as nicotinic acid-GPR109a or linoleoyl ethanolamide-GPR119 and inferred interactions of interest including oleanolic acid-GABRG2 and alpha-CEHC-THRB. Eleven metabolites were tested for bioactivity in vitro using human primary cell-types. By expanding the universe of possible microbial metabolite-host protein interactions, we provide multiple drug targets for potential immune-therapies.}, }
@article {pmid33671853, year = {2021}, author = {Huang, E and Kim, S and Ahn, T}, title = {Deep Learning for Integrated Analysis of Insulin Resistance with Multi-Omics Data.}, journal = {Journal of personalized medicine}, volume = {11}, number = {2}, pages = {}, pmid = {33671853}, issn = {2075-4426}, support = {P0009477, 2020//This research is supported through the Ministry of Trade, Industry and Energy(MOTIE)/ ; }, abstract = {Technological advances in next-generation sequencing (NGS) have made it possible to uncover extensive and dynamic alterations in diverse molecular components and biological pathways across healthy and diseased conditions. Large amounts of multi-omics data originating from emerging NGS experiments require feature engineering, which is a crucial step in the process of predictive modeling. The underlying relationship among multi-omics features in terms of insulin resistance is not well understood. In this study, using the multi-omics data of type II diabetes from the Integrative Human Microbiome Project, from 10,783 features, we conducted a data analytic approach to elucidate the relationship between insulin resistance and multi-omics features, including microbiome data. To better explain the impact of microbiome features on insulin classification, we used a developed deep neural network interpretation algorithm for each microbiome feature's contribution to the discriminative model output in the samples.}, }
@article {pmid33517907, year = {2021}, author = {Blaustein, RA and Michelitsch, LM and Glawe, AJ and Lee, H and Huttelmaier, S and Hellgeth, N and Ben Maamar, S and Hartmann, EM}, title = {Toothbrush microbiomes feature a meeting ground for human oral and environmental microbiota.}, journal = {Microbiome}, volume = {9}, number = {1}, pages = {32}, pmid = {33517907}, issn = {2049-2618}, support = {TL1 TR001423/TR/NCATS NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Aged ; *Built Environment ; Drug Resistance, Microbial/drug effects/genetics ; Humans ; Metagenome/drug effects/genetics ; *Microbiota/drug effects/genetics ; Middle Aged ; Mouth/drug effects/*microbiology ; *Toothbrushing ; Triclosan/pharmacology ; Young Adult ; }, abstract = {BACKGROUND: While indoor microbiomes impact our health and well-being, much remains unknown about taxonomic and functional transitions that occur in human-derived microbial communities once they are transferred away from human hosts. Toothbrushes are a model to investigate the potential response of oral-derived microbiota to conditions of the built environment. Here, we characterize metagenomes of toothbrushes from 34 subjects to define the toothbrush microbiome and resistome and possible influential factors.<br><br>RESULTS: Toothbrush microbiomes often comprised a dominant subset of human oral taxa and less&#xa0;abundant or&#xa0;site-specific environmental strains. Although toothbrushes contained lower taxonomic diversity than oral-associated counterparts (determined by comparison with the Human Microbiome Project), they had relatively broader antimicrobial resistance gene (ARG) profiles. Toothbrush resistomes were enriched with a variety of ARGs, notably those conferring multidrug efflux and putative resistance to triclosan, which were primarily attributable to versatile environmental taxa. Toothbrush microbial communities and resistomes correlated with a variety of factors linked to personal health, dental hygiene, and bathroom features.<br><br>CONCLUSIONS: Selective pressures in the built environment may shape the dynamic mixture of human (primarily oral-associated) and environmental microbiota that encounter each other on toothbrushes. Harboring a microbial diversity and resistome distinct from human-associated counterparts suggests toothbrushes could potentially serve as a reservoir that may enable the transfer of ARGs. Video abstract.}, }
@article {pmid33499991, year = {2020}, author = {Sidiropoulos, DN and Al-Ghalith, GA and Shields-Cutler, RR and Ward, TL and Johnson, AJ and Vangay, P and Knights, D and Kashyap, PC and Xian, Y and Ramer-Tait, AE and Clayton, JB}, title = {Wild primate microbiomes prevent weight gain in germ-free mice.}, journal = {Animal microbiome}, volume = {2}, number = {1}, pages = {16}, pmid = {33499991}, issn = {2524-4671}, support = {R01 DK114007/DK/NIDDK NIH HHS/United States ; T32 DA007097/DA/NIDA NIH HHS/United States ; T32 DA007097-32/DA/NIDA NIH HHS/United States ; }, abstract = {BACKGROUND: The gut microbiome harbors trillions of bacteria that play a major role in dietary nutrient extraction and host metabolism. Metabolic diseases such as obesity and diabetes are associated with shifts in microbiome composition and have been on the rise in Westernized or highly industrialized countries. At the same time, Westernized diets low in dietary fiber have been shown to cause loss of gut microbial diversity. However, the link between microbiome composition, loss of dietary fiber, and obesity has not been well defined.<br><br>RESULTS: To study the interactions between gut microbiota, dietary fiber, and weight gain, we transplanted captive and wild douc gut microbiota into germ-free mice and then exposed them to either a high- or low-fiber diet. The group receiving captive douc microbiota gained significantly more weight, regardless of diet, while mice receiving a high-fiber diet and wild douc microbiota remained lean. In the presence of a low-fiber diet, the wild douc microbiota partially prevented weight gain. Using 16S rRNA gene amplicon sequencing we identified key bacterial taxa in each group, specifically a high relative abundance of Bacteroides and Akkermansia in captive douc FMT mice and a higher relative abundance of Lactobacillus and Clostridium in the wild douc FMT mice.<br><br>CONCLUSIONS: In the context of our germ-free mouse experiment, wild douc microbiota could serve as a reservoir for microbes for cross-species transplants. Our results suggest that wild douc microbiota are tailored to diverse fiber diets and can prevent weight gain when exposed to a native diet.}, }
@article {pmid33498226, year = {2021}, author = {Garcia, EM and Serrano, MG and Edupuganti, L and Edwards, DJ and Buck, GA and Jefferson, KK}, title = {Sequence Comparison of Vaginolysin from Different Gardnerella Species.}, journal = {Pathogens (Basel, Switzerland)}, volume = {10}, number = {2}, pages = {}, pmid = {33498226}, issn = {2076-0817}, support = {UH2 AI083263/AI/NIAID NIH HHS/United States ; U54 DE023786/NH/NIH HHS/United States ; U54 HD080784/HD/NICHD NIH HHS/United States ; R01 HD092415/HD/NICHD NIH HHS/United States ; UH3 AI083263/AI/NIAID NIH HHS/United States ; U54 DE023786/DE/NIDCR NIH HHS/United States ; }, abstract = {Gardnerella vaginalis has recently been split into 13 distinct species. In this study, we tested the hypotheses that species-specific variations in the vaginolysin (VLY) amino acid sequence could influence the interaction between the toxin and vaginal epithelial cells and that VLY variation may be one factor that distinguishes less virulent or commensal strains from more virulent strains. This was assessed by bioinformatic analyses of publicly available Gardnerella spp. sequences and quantification of cytotoxicity and cytokine production from purified, recombinantly produced versions of VLY. After identifying conserved differences that could distinguish distinct VLY types, we analyzed metagenomic data from a cohort of female subjects from the Vaginal Human Microbiome Project to investigate whether these different VLY types exhibited any significant associations with symptoms or Gardnerella spp.-relative abundance in vaginal swab samples. While Type 1 VLY was most prevalent among the subjects and may be associated with increased reports of symptoms, subjects with Type 2 VLY dominant profiles exhibited increased relative Gardnerella spp. abundance. Our findings suggest that amino acid differences alter the interaction of VLY with vaginal keratinocytes, which may potentiate differences in bacterial vaginosis (BV) immunopathology in vivo.}, }
@article {pmid33398950, year = {2020}, author = {Duan, Y and Wang, S and Chen, Y and Yang, R and Li, H and Zhu, H and Tong, Y and Wu, W and Fu, Y and Hu, S and Wang, J and Xin, Y and Zhao, F and Bao, Y and Zhang, W and Li, J and Zeng, M and Niu, H and Zhou, X and Li, Y and Cui, S and Yuan, J and Li, J and Wang, J and Liu, D and Ni, M and Sun, Q and Deng, Y and Zhu, B}, title = {[Expert consensus on microbiome sequencing and analysis].}, journal = {Sheng wu gong cheng xue bao = Chinese journal of biotechnology}, volume = {36}, number = {12}, pages = {2516-2524}, doi = {10.13345/j.cjb.200386}, pmid = {33398950}, issn = {1872-2075}, mesh = {China ; Consensus ; Humans ; Industry ; *Microbiota ; }, abstract = {In the past ten years, the research and application of microbiome has continued to increase. The microbiome has gradually become the research focus in the fields of life science, environmental science, and medicine. Meanwhile, many countries and organizations around the world are launching their own microbiome projects and conducting a multi-faceted layout, striving to gain a strategic position in this promising field. In addition, whether it is scientific research or industrial applications, there has been a climax of research and a wave of investment and financing, accordingly, products and services related to the microbiome are constantly emerging. However, due to the rapid development of microbiome sequencing and analysis related technologies and methods, the research and application from various countries have not yet unified on the standards of technology, programs, and data. Domestic industry participants also have insufficient understanding of the microbiome. New methods, technologies, and theories have not yet been fully accepted and used. In addition, some of the existing standards and guidelines are too general with poor practicality. This not only causes obstacles in the integration of scientific research data and waste of resources, but also gives related companies unfair competition opportunity. More importantly, China still lacks national standards related to the microbiome, and the national microbiome project is still in the process of preparation. In this context, the experts and practitioners of the microbiome worked together and developed the consensus of experts. It can not only guide domestic scientific research and industrial institutions to regulate the production, learning and research of the microbiome, the application can also provide reference technical basis for the relevant national functional departments, protect the scale and standardized corporate company's interests, strengthen industry self-discipline, avoid unregulated enterprises from disrupting the market, and ultimately promote the benign development of microbiome-related industries.}, }
@article {pmid33323705, year = {2020}, author = {Gomes, J&#xc1;P and Frizon, L and Demeda, VF}, title = {Ocular Surface Microbiome in Health and Disease.}, journal = {Asia-Pacific journal of ophthalmology (Philadelphia, Pa.)}, volume = {9}, number = {6}, pages = {505-511}, pmid = {33323705}, issn = {2162-0989}, mesh = {Bacteria/*isolation &amp; purification ; Eye/*microbiology ; Humans ; Microbiota/*genetics ; RNA, Ribosomal, 16S/*genetics/metabolism ; }, abstract = {The ocular surface is exposed continuously to the environment and, as a consequence, to a variety of different microbes. After the results of the Human Microbiome Project became publicly available, international research groups started to focus interest on exploring the ocular surface microbiome and its physiopathological relationship to the eye. For example, numerous research studies the existence of the ocular surface's bacterial flora, typically gathering cultures from healthy patients and finding few variations in the bacterial species. More recently, culture-independent methods, including 16S ribosomal ribonucleic acid (rRNA) gene sequencing, are being used to define the ocular microbiome. These newer methods suggest that the microbial communities have a greater diversity than previously reported. These communities seem to serve an immune-modulating function and maintain relationships with other microbes and organs, even distant ones. This review summarizes the literature exploring the ocular microbiome, both in health and in different diseases.}, }
@article {pmid33323129, year = {2020}, author = {Utter, DR and Borisy, GG and Eren, AM and Cavanaugh, CM and Mark Welch, JL}, title = {Metapangenomics of the oral microbiome provides insights into habitat adaptation and cultivar diversity.}, journal = {Genome biology}, volume = {21}, number = {1}, pages = {293}, pmid = {33323129}, issn = {1474-760X}, support = {P30 DK042086/DK/NIDDK NIH HHS/United States ; R01 DE022586/DE/NIDCR NIH HHS/United States ; UL1 TR001102/TR/NCATS NIH HHS/United States ; }, mesh = {Bacteria/*genetics ; Chromosome Mapping ; Haemophilus parainfluenzae/genetics ; Humans ; *Metagenome ; Microbiota/*genetics ; Micrococcaceae/genetics ; Mouth/*microbiology ; RNA, Ribosomal, 16S/genetics ; }, abstract = {BACKGROUND: The increasing availability of microbial genomes and environmental shotgun metagenomes provides unprecedented access to the genomic differences within related bacteria. The human oral microbiome with its diverse habitats and abundant, relatively well-characterized microbial inhabitants presents an opportunity to investigate bacterial population structures at an ecosystem scale.<br><br>RESULTS: Here, we employ a metapangenomic approach that combines public genomes with Human Microbiome Project (HMP) metagenomes to study the diversity of microbial residents of three oral habitats: tongue dorsum, buccal mucosa, and supragingival plaque. For two exemplar taxa, Haemophilus parainfluenzae and the genus Rothia, metapangenomes reveal distinct genomic groups based on shared genome content. H. parainfluenzae genomes separate into three distinct subgroups with differential abundance between oral habitats. Functional enrichment analyses identify an operon encoding oxaloacetate decarboxylase as diagnostic for the tongue-abundant subgroup. For the genus Rothia, grouping by shared genome content recapitulates species-level taxonomy and habitat preferences. However, while most R. mucilaginosa are restricted to the tongue as expected, two genomes represent a cryptic population of R. mucilaginosa in many buccal mucosa samples. For both H. parainfluenzae and the genus Rothia, we identify not only limitations in the ability of cultivated organisms to represent populations in their native environment, but also specifically which cultivar gene sequences are absent or ubiquitous.<br><br>CONCLUSIONS: Our findings provide insights into population structure and biogeography in the mouth and form specific hypotheses about habitat adaptation. These results illustrate the power of combining metagenomes and pangenomes to investigate the ecology and evolution of bacteria across analytical scales.}, }
@article {pmid33322780, year = {2020}, author = {Oliveira, BFR and Lopes, IR and Canellas, ALB and Muricy, G and Dobson, ADW and Laport, MS}, title = {Not That Close to Mommy: Horizontal Transmission Seeds the Microbiome Associated with the Marine Sponge Plakina cyanorosea.}, journal = {Microorganisms}, volume = {8}, number = {12}, pages = {}, pmid = {33322780}, issn = {2076-2607}, abstract = {Marine sponges are excellent examples of invertebrate-microbe symbioses. In this holobiont, the partnership has elegantly evolved by either transmitting key microbial associates through the host germline and/or capturing microorganisms from the surrounding seawater. We report here on the prokaryotic microbiota during different developmental stages of Plakina cyanorosea and their surrounding environmental samples by a 16S rRNA metabarcoding approach. In comparison with their source adults, larvae housed slightly richer and more diverse microbial communities, which are structurally more related to the environmental microbiota. In addition to the thaumarchaeal Nitrosopumilus, parental sponges were broadly dominated by Alpha- and Gamma-proteobacteria, while the offspring were particularly enriched in the Vibrionales, Alteromonodales, Enterobacterales orders and the Clostridia and Bacteroidia classes. An enterobacterial operational taxonomic unit (OTU) was the dominant member of the strict core microbiota. The most abundant and unique OTUs were not significantly enriched amongst the microbiomes from host specimens included in the sponge microbiome project. In a wider context, Oscarella and Plakina are the sponge genera with higher divergence in their associated microbiota compared to their Homoscleromorpha counterparts. Our results indicate that P. cyanorosea is a low microbial abundance sponge (LMA), which appears to heavily depend on the horizontal transmission of its microbial partners that likely help the sponge host in the adaptation to its habitat.}, }
@article {pmid33307384, year = {2021}, author = {Ghemrawi, M and Torres, AR and Duncan, G and Colwell, R and Dadlani, M and McCord, B}, title = {The genital microbiome and its potential for detecting sexual assault.}, journal = {Forensic science international. Genetics}, volume = {51}, number = {}, pages = {102432}, doi = {10.1016/j.fsigen.2020.102432}, pmid = {33307384}, issn = {1878-0326}, mesh = {Adult ; Aged ; DNA, Bacterial/genetics ; Female ; High-Throughput Nucleotide Sequencing ; Humans ; Male ; Metagenomics ; *Microbiota ; Middle Aged ; Penis/*microbiology ; Pilot Projects ; Sequence Analysis, DNA ; *Sex Offenses ; Skin/microbiology ; Vagina/*microbiology ; Young Adult ; }, abstract = {Since its inception, the Human Microbiome Project (HMP) has provided key discoveries that can be applied to forensics, in addition to those of obvious medical value. Whether for postmortem interval estimation, geolocation, or human identification, there are many applications of the microbiome as an investigative lead for forensic casework. The human skin microbiome has shown great potential for use in studies of transfer and human identification, however there has been little focus on the genital microbiome, in particular penile skin which differs from other body sites. Our preliminary data on both the penile and vaginal microbiome demonstrates potential value in cases of sexual assault. In this study we describe genital microbial signatures based on the analysis of five male and five female genital samples and compare these results to those from longitudinal studies. Selected taxa, e.g., Gardnerella, Lactobacilli, Finegoldia, Peptoniphilus, and Anaerococci, are shown to be candidate constituents of the genital microbiome that merit investigation for use in sexual assault casework.}, }
@article {pmid33305317, year = {2021}, author = {Creasy, HH and Felix, V and Aluvathingal, J and Crabtree, J and Ifeonu, O and Matsumura, J and McCracken, C and Nickel, L and Orvis, J and Schor, M and Giglio, M and Mahurkar, A and White, O}, title = {HMPDACC: a Human Microbiome Project Multi-omic data resource.}, journal = {Nucleic acids research}, volume = {49}, number = {D1}, pages = {D734-D742}, pmid = {33305317}, issn = {1362-4962}, support = {OT3 OD025459/OD/NIH HHS/United States ; U54 DK102556/DK/NIDDK NIH HHS/United States ; U54 HD080784/HD/NICHD NIH HHS/United States ; U54 DK102557/DK/NIDDK NIH HHS/United States ; U01 HG004866/HG/NHGRI NIH HHS/United States ; R24 DK110499/DK/NIDDK NIH HHS/United States ; }, mesh = {*Databases, Genetic ; Humans ; Internet ; *Microbiota ; Search Engine ; }, abstract = {The Human Microbiome Project (HMP) explored microbial communities of the human body in both healthy and disease states. Two phases of the HMP (HMP and iHMP) together generated >48TB of data (public and controlled access) from multiple, varied omics studies of both the microbiome and associated hosts. The Human Microbiome Project Data Coordination Center (HMPDACC) was established to provide a portal to access data and resources produced by the HMP. The HMPDACC provides a unified data repository, multi-faceted search functionality, analysis pipelines and standardized protocols to facilitate community use of HMP data. Recent efforts have been put toward making HMP data more findable, accessible, interoperable and reusable. HMPDACC resources are freely available at www.hmpdacc.org.}, }
@article {pmid33290720, year = {2021}, author = {Durrant, MG and Bhatt, AS}, title = {Automated Prediction and Annotation of Small Open Reading Frames in Microbial Genomes.}, journal = {Cell host &amp; microbe}, volume = {29}, number = {1}, pages = {121-131.e4}, pmid = {33290720}, issn = {1934-6069}, support = {P30 CA124435/CA/NCI NIH HHS/United States ; R01 AI143757/AI/NIAID NIH HHS/United States ; R01 AI148623/AI/NIAID NIH HHS/United States ; }, mesh = {Bacteria/*genetics ; Bacterial Proteins/genetics ; Computational Biology ; Deep Learning ; *Genome, Bacterial ; Humans ; Markov Chains ; Microbiota ; Models, Theoretical ; *Molecular Sequence Annotation ; *Open Reading Frames ; }, abstract = {Small open reading frames (smORFs) and their encoded microproteins play central roles in microbes. However, there is a vast unexplored space of smORFs within human-associated microbes. A recent bioinformatic analysis used evolutionary conservation signals to enhance prediction of small protein families. To facilitate the annotation of specific smORFs, we introduce SmORFinder. This tool combines profile hidden Markov models of each smORF family and deep learning models that better generalize to smORF families not seen in the training set, resulting in predictions enriched for Ribo-seq translation signals. Feature importance analysis reveals that the deep learning models learn to identify Shine-Dalgarno sequences, deprioritize the wobble position in each codon, and group codon synonyms found in the codon table. A core-genome analysis of 26 bacterial species identifies several core smORFs of unknown function. We pre-compute smORF annotations for thousands of RefSeq isolate genomes and Human Microbiome Project metagenomes and provide these data through a public web portal.}, }
@article {pmid33281440, year = {2020}, author = {Joseph, N and Clayton, JB and Hoops, SL and Linhardt, CA and Mohd Hashim, A and Mohd Yusof, BN and Kumar, S and Amin Nordin, S}, title = {Alteration of the Gut Microbiome in Normal and Overweight School Children from Selangor with Lactobacillus Fermented Milk Administration.}, journal = {Evolutionary bioinformatics online}, volume = {16}, number = {}, pages = {1176934320965943}, pmid = {33281440}, issn = {1176-9343}, abstract = {Childhood obesity is a serious public health problem worldwide. Perturbations in the gut microbiota composition have been associated with the development of obesity in both children and adults. Probiotics, on the other hand, are proven to restore the composition of the gut microbiome which helps reduce the development of obesity. However, data on the effect of probiotics on gut microbiota and its association with childhood obesity is limited. This study aims to determine the effect of probiotics supplement intervention on gut microbiota profiles in obese and normal-weight children. A total of 37 children, 17 normal weight, and 20 overweight school children from a government school in Selangor were selected to participate in this study. Participants were further divided into intervention and control groups. The intervention groups received daily probiotic drinks while the control groups continued eating their typical diet. Fecal samples were collected from the participants for DNA extraction. The hypervariable V3 and V4 regions of 16S rRNA gene were amplified and sequenced using the Illumina MiSeq platform. No significant differences in alpha diversity were observed between normal weight and obese children in terms of the Shannon Index for evenness or species richness. However, a higher intervention effect on alpha diversity was observed among normal-weight participants compared to obese. The participants' microbiome was found to fluctuate throughout the study. Analysis of the taxa at species level showed an increase in Bacteroides ovatus among the normal weight cohort. Genus-level comparison revealed a rise in genus Lachnospira and Ruminococcus in the overweight participants after intervention, compared to the normal-weight participants. The probiotics intervention causes an alteration in gut microbiota composition in both normal and overweight children. Though the association could not be defined statistically, this study has provided an improved understanding of the intervention effect of probiotics on gut microbiome dysbiosis in an underrepresented population.}, }
@article {pmid33215610, year = {2020}, author = {Madi, N and Vos, M and Murall, CL and Legendre, P and Shapiro, BJ}, title = {Does diversity beget diversity in microbiomes?.}, journal = {eLife}, volume = {9}, number = {}, pages = {}, pmid = {33215610}, issn = {2050-084X}, mesh = {*Biodiversity ; Biota/genetics ; Ecosystem ; High-Throughput Nucleotide Sequencing ; *Microbiota/genetics ; }, abstract = {Microbes are embedded in complex communities where they engage in a wide array of intra- and inter-specific interactions. The extent to which these interactions drive or impede microbiome diversity is not well understood. Historically, two contrasting hypotheses have been suggested to explain how species interactions could influence diversity. 'Ecological Controls' (EC) predicts a negative relationship, where the evolution or migration of novel types is constrained as niches become filled. In contrast, 'Diversity Begets Diversity' (DBD) predicts a positive relationship, with existing diversity promoting the accumulation of further diversity via niche construction and other interactions. Using high-throughput amplicon sequencing data from the Earth Microbiome Project, we provide evidence that DBD is strongest in low-diversity biomes, but weaker in more diverse biomes, consistent with biotic interactions initially favouring the accumulation of diversity (as predicted by DBD). However, as niches become increasingly filled, diversity hits a plateau (as predicted by EC).}, }
@article {pmid33117966, year = {2020}, author = {Mise, K and Iwasaki, W}, title = {Environmental Atlas of Prokaryotes Enables Powerful and Intuitive Habitat-Based Analysis of Community Structures.}, journal = {iScience}, volume = {23}, number = {10}, pages = {101624}, pmid = {33117966}, issn = {2589-0042}, abstract = {The recent prevalence of high-throughput sequencing has been producing numerous prokaryotic community structure datasets. Although the trait-based approach is useful to interpret those datasets from ecological perspectives, available trait information is biased toward culturable prokaryotes, especially those of clinical and public health relevance, and thus may not represent the breadth of microbiota found across many of Earth's environments. To facilitate habitat-based analysis free of such bias, here we report a ready-to-use prokaryotic habitat database, ProkAtlas. ProkAtlas comprehensively links 16S rRNA gene sequences to prokaryotic habitats, using public shotgun metagenome datasets. We also developed a computational pipeline for habitat-based analysis of given prokaryotic community structures. After confirmation of the method effectiveness using 16S rRNA gene sequence datasets from individual genomes and the Earth Microbiome Project, we showed its validness and effectiveness in drawing ecological insights by applying it to six empirical prokaryotic community datasets from soil, aquatic, and human gut samples.}, }
@article {pmid33077849, year = {2020}, author = {Sternes, PR and Martin, TM and Paley, M and Diamond, S and Asquith, MJ and Brown, MA and Rosenbaum, JT}, title = {HLA-A alleles including HLA-A29 affect the composition of the gut microbiome: a potential clue to the pathogenesis of birdshot retinochoroidopathy.}, journal = {Scientific reports}, volume = {10}, number = {1}, pages = {17636}, pmid = {33077849}, issn = {2045-2322}, support = {R01 EY029266/EY/NEI NIH HHS/United States ; EY029266/NH/NIH HHS/United States ; }, mesh = {Adult ; Aged ; *Alleles ; Birdshot Chorioretinopathy/*genetics/microbiology ; Female ; Gastrointestinal Microbiome/*genetics ; HLA-A Antigens/*genetics ; Humans ; Male ; *Metagenome ; Middle Aged ; Whole Genome Sequencing ; }, abstract = {Birdshot retinochoroidopathy occurs exclusively in individuals who are HLA-A29 positive. The mechanism to account for this association is unknown. The gut microbiome has been causally implicated in many immune-mediated diseases. We hypothesized that HLA-A29 would affect the composition of the gut microbiome, leading to a dysbiosis and immune-mediated eye disease. Fecal and intestinal biopsy samples were obtained from 107 healthy individuals from Portland, Oregon environs, 10 of whom were HLA-A29 positive, undergoing routine colonoscopy. Bacterial profiling was achieved via 16S rRNA metabarcoding. Publicly available whole meta-genome sequencing data from the Human Microbiome Project (HMP), consisting of 298 healthy controls mostly of US origin, were also interrogated. PERMANOVA and sparse partial least squares discriminant analysis (sPLSDA) demonstrated that subjects who were HLA-A29 positive differed in bacterial species composition (beta diversity) compared to HLA-A29 negative subjects in both the Portland (p = 0.019) and HMP cohorts (p = 0.0002). The Portland and HMP cohorts evidenced different subsets of bacterial species associated with HLA-A29 status, likely due to differences in the metagenomic techniques employed. The functional composition of the HMP cohort did not differ overall (p = 0.14) between HLA-A29 positive and negative subjects, although some distinct pathways such as heparan sulfate biosynthesis showed differences. As we and others have shown for various HLA alleles, the HLA allotype impacts the composition of the microbiome. We hypothesize that HLA-A29 may predispose chorioretinitis via an altered gut microbiome.}, }
@article {pmid33044333, year = {2021}, author = {Mancin, L and Rollo, I and Mota, JF and Piccini, F and Carletti, M and Susto, GA and Valle, G and Paoli, A}, title = {Optimizing Microbiota Profiles for Athletes.}, journal = {Exercise and sport sciences reviews}, volume = {49}, number = {1}, pages = {42-49}, doi = {10.1249/JES.0000000000000236}, pmid = {33044333}, issn = {1538-3008}, mesh = {Athletes ; *Gastrointestinal Microbiome ; Humans ; *Microbiota ; *Sports ; }, abstract = {Gut microbiome influences athletes' physiology, but because of the complexity of sport performance and the great intervariability of microbiome features, it is not reasonable to define a single healthy microbiota profile for athletes. We suggest the use of specific meta-omics analysis coupled with innovative computational systems to uncover the hidden association between microbes and athlete's physiology and predict personalized recommendation.}, }
@article {pmid33042093, year = {2020}, author = {Zelaya, AJ and Gerardo, NM and Blumer, LS and Beck, CW}, title = {The Bean Beetle Microbiome Project: A Course-Based Undergraduate Research Experience in Microbiology.}, journal = {Frontiers in microbiology}, volume = {11}, number = {}, pages = {577621}, pmid = {33042093}, issn = {1664-302X}, abstract = {Course-based undergraduate research experiences (CUREs) are an effective means of transforming the learning and teaching of science by involving students in the scientific process. The potential importance of the microbiome in shaping both environmental health and disease makes investigations of microbiomes an excellent teaching tool for undergraduate microbiology. Here, we present a CURE based on the microbiome of the bean beetle (Callosobruchus maculatus), a model system for undergraduate laboratory education. Despite the extensive research literature on bean beetles, little is known about their microbiome, making them an ideal system for a discovery-based CURE. In the CURE, students acquire microbiological technical skills by characterizing both culturable and unculturable members of the beetle gut-microbial community. Students plate beetle gut homogenates on different media, describe the colonies that are formed to estimate taxonomic diversity, extract DNA from colonies of interest, PCR amplify the16S rRNA gene for Sanger sequencing, and use the NCBI-nBLAST database to taxonomically classify sequences. Additionally, students extract total DNA from beetle gut homogenates for high-throughput paired-end sequencing and perform bioinformatic and statistical analyses of bacterial communities using a combination of open-access data processing software. Each activity allows students to engage with studies of microbiomes in a real-world context, to apply concepts and laboratory techniques to investigate either student or faculty-driven research questions, and to gain valuable experiences working with large high-throughput datasets. The CURE is designed such that it can be implemented over either 6-weeks (half semester) or 12-weeks (full semester), allowing for flexibility within the curriculum. Furthermore, student-generated data from the CURE (including bacterial colony phenotypic data, full-length 16S rRNA gene sequences from cultured isolates, and bacterial community sequences from gut homogenates) has been compiled in a continuously curated open-access database on the Bean Beetle Microbiome Project website, facilitating the generation of broader research questions across laboratory classrooms.}, }
@article {pmid32993284, year = {2020}, author = {Ervin, SM and Simpson, JB and Gibbs, ME and Creekmore, BC and Lim, L and Walton, WG and Gharaibeh, RZ and Redinbo, MR}, title = {Structural Insights into Endobiotic Reactivation by Human Gut Microbiome-Encoded Sulfatases.}, journal = {Biochemistry}, volume = {59}, number = {40}, pages = {3939-3950}, doi = {10.1021/acs.biochem.0c00711}, pmid = {32993284}, issn = {1520-4995}, mesh = {Bacteria/chemistry/*enzymology/genetics/metabolism ; Catalytic Domain ; Feces/microbiology ; *Gastrointestinal Microbiome ; Genes, Bacterial ; Humans ; *Microbiota ; Models, Molecular ; Protein Conformation ; Sulfatases/chemistry/genetics/*metabolism ; }, abstract = {Phase II drug metabolism inactivates xenobiotics and endobiotics through the addition of either a glucuronic acid or sulfate moiety prior to excretion, often via the gastrointestinal tract. While the human gut microbial β-glucuronidase enzymes that reactivate glucuronide conjugates in the intestines are becoming well characterized and even controlled by targeted inhibitors, the sulfatases encoded by the human gut microbiome have not been comprehensively examined. Gut microbial sulfatases are poised to reactivate xenobiotics and endobiotics, which are then capable of undergoing enterohepatic recirculation or exerting local effects on the gut epithelium. Here, using protein structure-guided methods, we identify 728 distinct microbiome-encoded sulfatase proteins from the 4.8 million unique proteins present in the Human Microbiome Project Stool Sample database and 1766 gut microbial sulfatases from the 9.9 million sequences in the Integrated Gene Catalogue. We purify a representative set of these sulfatases, elucidate crystal structures, and pinpoint unique structural motifs essential to endobiotic sulfate processing. Gut microbial sulfatases differentially process sulfated forms of the neurotransmitters serotonin and dopamine, and the hormones melatonin, estrone, dehydroepiandrosterone, and thyroxine in a manner dependent both on variabilities in active site architecture and on markedly distinct oligomeric states. Taken together, these data provide initial insights into the structural and functional diversity of gut microbial sulfatases, providing a path toward defining the roles these enzymes play in health and disease.}, }
@article {pmid32976571, year = {2021}, author = {Gail, MH and Wan, Y and Shi, J}, title = {Power of Microbiome Beta-Diversity Analyses Based on Standard Reference Samples.}, journal = {American journal of epidemiology}, volume = {190}, number = {3}, pages = {439-447}, pmid = {32976571}, issn = {1476-6256}, mesh = {*Body Mass Index ; Feces/microbiology ; Humans ; Microbiota/*physiology ; Nose/microbiology ; Reference Standards ; Saliva/microbiology ; Skin/microbiology ; }, abstract = {A simple method to analyze microbiome beta-diversity computes mean beta-diversity distances from a test sample to standard reference samples. We used reference stool and nasal samples from the Human Microbiome Project and regressed an outcome on mean distances (2 degrees-of-freedom (df) test) or additionally on squares and cross-product of mean distances (5-df test). We compared the power of 2-df and 5-df tests with the microbiome regression-based kernel association test (MiRKAT). In simulations, MiRKAT had moderately greater power than the 2-df test for discriminating skin versus saliva and skin versus nasal samples, but differences were negligible for skin versus stool and stool versus nasal samples. The 2-df test had slightly greater power than MiRKAT for Dirichlet multinomial samples. In associating body mass index with beta-diversity in stool samples from the American Gut Project, the 5-df test yielded smaller P values than MiRKAT for most taxonomic levels and beta-diversity measures. Unlike procedures like MiRKAT that are based on the beta-diversity matrix, mean distances to reference samples can be analyzed with standard statistical tools and shared or meta-analyzed without sharing primary DNA data. Our data indicate that standard reference tests have power comparable to MiRKAT's (and to permutational multivariate analysis of variance), but more simulations and applications are needed to confirm this.}, }
@article {pmid32966309, year = {2020}, author = {Walters, KE and Martiny, JBH}, title = {Alpha-, beta-, and gamma-diversity of bacteria varies across habitats.}, journal = {PloS one}, volume = {15}, number = {9}, pages = {e0233872}, pmid = {32966309}, issn = {1932-6203}, mesh = {Bacteria/*classification ; Databases, Genetic ; *Ecosystem ; Microbiota ; RNA, Ribosomal, 16S/genetics ; *Soil Microbiology ; }, abstract = {Bacteria are essential parts of ecosystems and are the most diverse organisms on the planet. Yet, we still do not know which habitats support the highest diversity of bacteria across multiple scales. We analyzed alpha-, beta-, and gamma-diversity of bacterial assemblages using 11,680 samples compiled by the Earth Microbiome Project. We found that soils contained the highest bacterial richness within a single sample (alpha-diversity), but sediment assemblages displayed the highest gamma-diversity. Sediment, biofilms/mats, and inland water exhibited the most variation in community composition among geographic locations (beta-diversity). Within soils, agricultural lands, hot deserts, grasslands, and shrublands contained the highest richness, while forests, cold deserts, and tundra biomes consistently harbored fewer bacterial species. Surprisingly, agricultural soils encompassed similar levels of beta-diversity as other soil biomes. These patterns were robust to the alpha- and beta- diversity metrics used and the taxonomic binning approach. Overall, the results support the idea that spatial environmental heterogeneity is an important driver of bacterial diversity.}, }
@article {pmid32938501, year = {2020}, author = {Zhang, Z and Wang, J and Wang, J and Wang, J and Li, Y}, title = {Estimate of the sequenced proportion of the global prokaryotic genome.}, journal = {Microbiome}, volume = {8}, number = {1}, pages = {134}, pmid = {32938501}, issn = {2049-2618}, mesh = {Archaea/classification/genetics/isolation &amp; purification ; Bacteria/classification/genetics/isolation &amp; purification ; Databases, Genetic ; *Earth, Planet ; Genome/*genetics ; Genomics/*statistics &amp; numerical data ; Microbiota/*genetics ; Prokaryotic Cells/*classification/*metabolism ; Sequence Alignment ; Sequence Analysis/*statistics &amp; numerical data ; }, abstract = {BACKGROUND: Sequencing prokaryotic genomes has revolutionized our understanding of the many roles played by microorganisms. However, the cell and taxon proportions of genome-sequenced bacteria or archaea on earth remain unknown. This study aimed to explore this basic question using large-scale alignment between the sequences released by the Earth Microbiome Project and 155,810 prokaryotic genomes from public databases.<br><br>RESULTS: Our results showed that the median proportions of the genome-sequenced cells and taxa (at 100% identities in the 16S-V4 region) in different biomes reached 38.1% (16.4-86.3%) and 18.8% (9.1-52.6%), respectively. The sequenced proportions of the prokaryotic genomes in biomes were significantly negatively correlated with the alpha diversity indices, and the proportions sequenced in host-associated biomes were significantly higher than those in free-living biomes. Due to a set of cosmopolitan OTUs that are found in multiple samples and preferentially sequenced, only 2.1% of the global prokaryotic taxa are represented by sequenced genomes. Most of the biomes were occupied by a few predominant taxa with a high relative abundance and much higher genome-sequenced proportions than numerous rare taxa.<br><br>CONCLUSIONS: These results reveal the current situation of prokaryotic genome sequencing for earth biomes, provide a more reasonable and efficient exploration of prokaryotic genomes, and promote our understanding of microbial ecological functions. Video Abstract.}, }
@article {pmid32938362, year = {2020}, author = {Guerrini, V and Louza, FA and Rosone, G}, title = {Metagenomic analysis through the extended Burrows-Wheeler transform.}, journal = {BMC bioinformatics}, volume = {21}, number = {Suppl 8}, pages = {299}, pmid = {32938362}, issn = {1471-2105}, mesh = {*Algorithms ; High-Throughput Nucleotide Sequencing/*methods ; Humans ; Metagenomics/*methods ; Reproducibility of Results ; }, abstract = {BACKGROUND: The development of Next Generation Sequencing (NGS) has had a major impact on the study of genetic sequences. Among problems that researchers in the field have to face, one of the most challenging is the taxonomic classification of metagenomic reads, i.e., identifying the microorganisms that are present in a sample collected directly from the environment. The analysis of environmental samples (metagenomes) are particularly important to figure out the microbial composition of different ecosystems and it is used in a wide variety of fields: for instance, metagenomic studies in agriculture can help understanding the interactions between plants and microbes, or in ecology, they can provide valuable insights into the functions of environmental communities.<br><br>RESULTS: In this paper, we describe a new lightweight alignment-free and assembly-free framework for metagenomic classification that compares each unknown sequence in the sample to a collection of known genomes. We take advantage of the combinatorial properties of an extension of the Burrows-Wheeler transform, and we sequentially scan the required data structures, so that we can analyze unknown sequences of large collections using little internal memory. The tool LiME (Lightweight Metagenomics via eBWT) is available at https://github.com/veronicaguerrini/LiME .<br><br>CONCLUSIONS: In order to assess the reliability of our approach, we run several experiments on NGS data from two simulated metagenomes among those provided in benchmarking analysis and on a real metagenome from the Human Microbiome Project. The experiment results on the simulated data show that LiME is competitive with the widely used taxonomic classifiers. It achieves high levels of precision and specificity - e.g. 99.9% of the positive control reads are correctly assigned and the percentage of classified reads of the negative control is less than 0.01% - while keeping a high sensitivity. On the real metagenome, we show that LiME is able to deliver classification results comparable to that of MagicBlast. Overall, the experiments confirm the effectiveness of our method and its high accuracy even in negative control samples.}, }
@article {pmid32917276, year = {2020}, author = {Golovko, G and Kamil, K and Albayrak, L and Nia, AM and Duarte, RSA and Chumakov, S and Fofanov, Y}, title = {Identification of multidimensional Boolean patterns in microbial communities.}, journal = {Microbiome}, volume = {8}, number = {1}, pages = {131}, pmid = {32917276}, issn = {2049-2618}, support = {R03 DE028596/DE/NIDCR NIH HHS/United States ; }, mesh = {Bacteria/isolation &amp; purification ; Humans ; *Microbial Interactions ; *Microbiota/physiology ; }, abstract = {BACKGROUND: Identification of complex multidimensional interaction patterns within microbial communities is the key to understand, modulate, and design beneficial microbiomes. Every community has members that fulfill an essential function affecting multiple other community members through secondary metabolism. Since microbial community members are often simultaneously involved in multiple relations, not all interaction patterns for such microorganisms are expected to exhibit a visually uninterrupted pattern. As a result, such relations cannot be detected using traditional correlation, mutual information, principal coordinate analysis, or covariation-based network inference approaches.<br><br>RESULTS: We present a novel pattern-specific method to quantify the strength and estimate the statistical significance of two-dimensional co-presence, co-exclusion, and one-way relation patterns between abundance profiles of two organisms as well as extend this approach to allow search and visualize three-, four-, and higher dimensional patterns. The proposed approach has been tested using 2380 microbiome samples from the Human Microbiome Project resulting in body site-specific networks of statistically significant 2D patterns as well as revealed the presence of 3D patterns in the Human Microbiome Project data.<br><br>CONCLUSIONS: The presented study suggested that search for Boolean patterns in the microbial abundance data needs to be pattern specific. The reported presence of multidimensional patterns (which cannot be reduced to a combination of two-dimensional patterns) suggests that multidimensional (multi-organism) relations may play important roles in the organization of microbial communities, and their detection (and appropriate visualization) may lead to a deeper understanding of the organization and dynamics of microbial communities. Video Abstract.}, }
@article {pmid32888342, year = {2020}, author = {Reyes-Gibby, CC and Wang, J and Zhang, L and Peterson, CB and Do, KA and Jenq, RR and Shelburne, S and Shah, DP and Chambers, MS and Hanna, EY and Yeung, SJ and Shete, S}, title = {Oral microbiome and onset of oral mucositis in patients with squamous cell carcinoma of the head and neck.}, journal = {Cancer}, volume = {126}, number = {23}, pages = {5124-5136}, pmid = {32888342}, issn = {1097-0142}, support = {RP160693//Cancer Prevention and Research Institute of Texas/ ; R01 CA131324/CA/NCI NIH HHS/United States ; P50 CA140388/CA/NCI NIH HHS/United States ; P50CA140388/CA/NCI NIH HHS/United States ; RP170259//Cancer Prevention and Research Institute of Texas/ ; UL1 TR003167/TR/NCATS NIH HHS/United States ; 1R01CA131324/CA/NCI NIH HHS/United States ; R01DE022891/DE/NIDCR NIH HHS/United States ; R21DE026837/DE/NIDCR NIH HHS/United States ; CA016672/CA/NCI NIH HHS/United States ; //Betty B. Marcus Chair in Cancer Prevention/ ; R21 DE026837/DE/NIDCR NIH HHS/United States ; R01 DE022891/DE/NIDCR NIH HHS/United States ; P30 CA016672/CA/NCI NIH HHS/United States ; }, mesh = {Aged ; Female ; Head and Neck Neoplasms/microbiology/*therapy ; Humans ; Male ; *Microbiota/drug effects/radiation effects ; Middle Aged ; RNA, Ribosomal, 16S ; Squamous Cell Carcinoma of Head and Neck/microbiology/*therapy ; Stomatitis/*etiology/microbiology ; Time Factors ; }, abstract = {BACKGROUND: Oral mucositis (OM) is a debilitating sequela for patients treated for squamous cell carcinoma of the head and neck (HNSCC). This study investigated whether oral microbial features before treatment or during treatment are associated with the time to onset of severe OM in patients with HNSCC.<br><br>METHODS: This was a cohort study of newly diagnosed patients with locoregional HNSCC who received chemotherapy with or without radiotherapy from April 2016 to September 2017. OM was based on the National Cancer Institute's Common Terminology Criteria for Adverse Events, version 4.0. The oral microbiome was characterized on the basis of the 16S ribosomal RNA V4 region with the Illumina platform. A mixture cure model was used to generate hazard ratios for the onset of severe OM.<br><br>RESULTS: Eighty-six percent of the patients developed OM (n&#xa0;=&#xa0;57 [33 nonsevere cases and 24 severe cases]) with a median time to onset of OM of 21 days. With adjustments for age, sex, and smoking status, genera abundance was associated with the hazard for the onset of severe OM as follows: 1) at the baseline (n&#xa0;=&#xa0;66), Cardiobacterium (P&#xa0;=&#xa0;.03) and Granulicatella (P&#xa0;=&#xa0;.04); 2) immediately before the development of OM (n&#xa0;=&#xa0;57), Prevotella (P&#xa0;=&#xa0;.03), Fusobacterium (P&#xa0;=&#xa0;.03), and Streptococcus (P&#xa0;=&#xa0;.01); and 3) immediately before the development of severe OM (n&#xa0;=&#xa0;24), Megasphaera (P&#xa0;=&#xa0;.0001) and Cardiobacterium (P&#xa0;=&#xa0;.03). There were no differences in &#x3b1;-diversity between the baseline samples and Human Microbiome Project data.<br><br>CONCLUSIONS: Changes in the abundance of genera over the course of treatment were associated with the onset of severe OM. The mechanism and therapeutic implications of these findings need to be investigated in future studies.}, }
@article {pmid32884579, year = {2020}, author = {Katongole, P and Sande, OJ and Joloba, M and Reynolds, SJ and Niyonzima, N}, title = {The human microbiome and its link in prostate cancer risk and pathogenesis.}, journal = {Infectious agents and cancer}, volume = {15}, number = {}, pages = {53}, pmid = {32884579}, issn = {1750-9378}, support = {D43 TW010132/TW/FIC NIH HHS/United States ; }, abstract = {There is growing evidence of the microbiome's role in human health and disease since the human microbiome project. The microbiome plays a vital role in influencing cancer risk and pathogenesis. Several studies indicate microbial pathogens to account for over 15-20% of all cancers. Furthermore, the interaction of the microbiota, especially the gut microbiota in influencing response to chemotherapy, immunotherapy, and radiotherapy remains an area of active research. Certain microbial species have been linked to the improved clinical outcome when on different cancer therapies. The recent discovery of the urinary microbiome has enabled the study to understand its connection to genitourinary malignancies, especially prostate cancer. Prostate cancer is the second most common cancer in males worldwide. Therefore research into understanding the factors and mechanisms associated with prostate cancer etiology, pathogenesis, and disease progression is of utmost importance. In this review, we explore the current literature concerning the link between the gut and urinary microbiome and prostate cancer risk and pathogenesis.}, }
@article {pmid32881767, year = {2020}, author = {Brenner, LA and Stamper, CE and Hoisington, AJ and Stearns-Yoder, KA and Stanislawksi, MA and Brostow, DP and Hoffmire, CA and Forster, JE and Schneider, AL and Postolache, TT and Lowry, CA}, title = {Microbial Diversity and Community Structures Among Those With Moderate to Severe TBI: A United States-Veteran Microbiome Project Study.}, journal = {The Journal of head trauma rehabilitation}, volume = {35}, number = {5}, pages = {332-341}, doi = {10.1097/HTR.0000000000000615}, pmid = {32881767}, issn = {1550-509X}, mesh = {*Brain Concussion/microbiology ; *Brain Injuries, Traumatic/microbiology ; *Gastrointestinal Microbiome ; Humans ; RNA, Ribosomal, 16S/genetics ; United States/epidemiology ; *Veterans ; }, abstract = {OBJECTIVE: To evaluate the association between distal moderate/severe traumatic brain injury (TBI) history and the human gut microbiome.<br><br>SETTING: Veterans Affairs Medical Center.<br><br>PARTICIPANTS: Veterans from the United States-Veteran Microbiome Project (US-VMP). Veterans with moderate/severe TBI (n = 34) were compared with (1) Veterans with a history of no TBI (n = 79) and (2) Veterans with a history of no TBI or mild TBI only (n = 297).<br><br>DESIGN: Microbiome analyses from 16S rRNA gene sequencing with gut microbiota function inferred using PICRUSt2.<br><br>MAIN MEASURES: &#x3b1;-Diversity and &#x3b2;-diversity of the gut microbiome, as well as taxonomic and functional signatures associated with moderate/severe TBI.<br><br>RESULTS: There were no significant differences in gut bacterial &#x3b1;- and &#x3b2;-diversity associated with moderate/severe TBI status. No differentially abundant taxa were identified when comparing samples from moderate/severe TBI to those with no TBI or no TBI/mild TBI.<br><br>CONCLUSION: Results suggest that moderate/severe TBI-related changes to the gut microbiome do not persist for years postinjury.}, }
@article {pmid32879794, year = {2020}, author = {Odogwu, NM and Olayemi, OO and Omigbodun, AO}, title = {The vaginal microbiome of sub-Saharan African women: revealing important gaps in the era of next-generation sequencing.}, journal = {PeerJ}, volume = {8}, number = {}, pages = {e9684}, pmid = {32879794}, issn = {2167-8359}, abstract = {Accurate characterization of the vaginal microbiome remains a fundamental goal of the Human Microbiome project (HMP). For over a decade, this goal has been made possible deploying high-throughput next generation sequencing technologies (NGS), which indeed has revolutionized medical research and enabled large-scale genomic studies. The 16S rRNA marker-gene survey is the most commonly explored approach for vaginal microbial community studies. With this approach, prior studies have elucidated substantial variations in the vaginal microbiome of women from different ethnicities. This review provides a comprehensive account of studies that have deployed this approach to describe the vaginal microbiota of African women in health and disease. On the basis of published data, the few studies reported from the African population are mainly in non-pregnant post pubertal women and calls for more detailed studies in pregnant and postnatal cohorts. We provide insight on the use of more sophisticated cutting-edge technologies in characterizing the vaginal microbiome. These technologies offer high-resolution detection of vaginal microbiome variations and community functional capabilities, which can shed light into several discrepancies observed in the vaginal microbiota of African women in an African population versus women of African descent in the diaspora.}, }
@article {pmid32815317, year = {2020}, author = {Nascimento Lemos, L and Manoharan, L and William Mendes, L and Monteiro Venturini, A and Satler Pylro, V and Tsai, SM}, title = {Metagenome assembled-genomes reveal similar functional profiles of CPR/Patescibacteria phyla in soils.}, journal = {Environmental microbiology reports}, volume = {12}, number = {6}, pages = {651-655}, doi = {10.1111/1758-2229.12880}, pmid = {32815317}, issn = {1758-2229}, support = {//Brazilian Microbiome Project/International ; 140032/2015-0//Conselho Nacional de Desenvolvimento Cient&#xed;fico e Tecnol&#xf3;gico/International ; 161931/2015-4//Conselho Nacional de Desenvolvimento Cient&#xed;fico e Tecnol&#xf3;gico/International ; Finance Code 001//Coordena&#xe7;&#xe3;o de Aperfei&#xe7;oamento de Pessoal de N&#xed;vel Superior/International ; 2014/50320-4//Funda&#xe7;&#xe3;o de Amparo &#xe0; Pesquisa do Estado de S&#xe3;o Paulo/International ; 2015/13546-7//Funda&#xe7;&#xe3;o de Amparo &#xe0; Pesquisa do Estado de S&#xe3;o Paulo/International ; 2016/18215-1//Funda&#xe7;&#xe3;o de Amparo &#xe0; Pesquisa do Estado de S&#xe3;o Paulo/International ; 2017/09643-2//Funda&#xe7;&#xe3;o de Amparo &#xe0; Pesquisa do Estado de S&#xe3;o Paulo/International ; 2017/24037-1//Funda&#xe7;&#xe3;o de Amparo &#xe0; Pesquisa do Estado de S&#xe3;o Paulo/International ; //Coordination for the Improvement of Higher Education Personnel/International ; //National Council for Scientific and Technological Development/International ; //S&#xe3;o Paulo Research Foundation/International ; }, mesh = {Bacteria/classification/*genetics/isolation &amp; purification ; Databases, Genetic ; Genome Size ; *Genome, Bacterial ; Metagenome ; Microbiota ; Phylogeny ; *Soil Microbiology ; }, abstract = {Soil microbiome is one of the most heterogeneous biological systems. State-of-the-art molecular approaches such as those based on single-amplified genomes (SAGs) and metagenome assembled-genomes (MAGs) are now improving our capacity for disentailing soil microbial-mediated processes. Here, we analysed publicly available datasets of soil microbial genomes and MAG's reconstructed from the Amazon's tropical soil (primary forest and pasture) and active layer of permafrost, aiming to evaluate their genome size. Our results suggest that the Candidate Phyla Radiation (CPR)/Patescibacteria phyla have genomes with an average size fourfold smaller than the mean identified in the RefSoil database, which lacks any representative of this phylum. Also, by analysing the potential metabolism of 888 soil microbial genomes, we show that CPR/Patescibacteria representatives share similar functional profiles, but different from other microbial phyla and are frequently neglected in the soil microbial surveys. Finally, we argue that the use of MAGs may be a better choice over SAGs to expand the soil microbial databases, like RefSoil.}, }
@article {pmid32717337, year = {2021}, author = {Chadha, J and Nandi, D and Atri, Y and Nag, A}, title = {Significance of human microbiome in breast cancer: Tale of an invisible and an invincible.}, journal = {Seminars in cancer biology}, volume = {70}, number = {}, pages = {112-127}, doi = {10.1016/j.semcancer.2020.07.010}, pmid = {32717337}, issn = {1096-3650}, mesh = {Animals ; Antineoplastic Agents/*administration &amp; dosage ; Breast Neoplasms/*drug therapy/microbiology ; Female ; *Gastrointestinal Microbiome ; Humans ; Prebiotics/*administration &amp; dosage ; *Precision Medicine ; }, abstract = {The human microbiome is a mysterious treasure of the body playing endless important roles in the well-being of the host metabolism, digestion, and immunity. On the other hand, it actively participates in the development of a variety of pathological conditions including cancer. With the Human Microbiome Project initiative, metagenomics, and next-generation sequencing technologies in place, the last decade has witnessed immense explorations and investigations on the enigmatic association of breast cancer with the human microbiome. However, the connection between the human microbiome and breast cancer remains to be explored in greater detail. In fact, there are several emerging questions such as whether the host microbiota contributes to disease initiation, or is it a consequence of the disease is an irrevocably important question that demands a valid answer. Since the microbiome is an extremely complex community, gaps still remain on how this vital microbial organ plays a role in orchestrating breast cancer development. Nevertheless, undeniable evidence from studies has pinpointed the presence of specific microbial elements of the breast and gut to play a role in governing breast cancer. It is still unclear if an alteration in microbiome/dysbiosis leads to breast cancer or is it vice versa. Though specific microbial signatures have been detected to be associated with various breast cancer subtypes, the structure and composition of a core "healthy" microbiome is yet to be established. Probiotics seem to be a promising antidote for targeted prevention and treatment of breast cancer. Interestingly, these microbial communities can serve as potential biomarkers for prognosis, diagnosis, and treatment of breast cancer, thereby leading to the rise of a completely new era of personalized medicine. This review is a humble attempt to summarize the research findings on the human microbiome and its relation to breast cancer.}, }
@article {pmid32684275, year = {2020}, author = {Joseph, TA and Pasarkar, AP and Pe'er, I}, title = {Efficient and Accurate Inference of Mixed Microbial Population Trajectories from Longitudinal Count Data.}, journal = {Cell systems}, volume = {10}, number = {6}, pages = {463-469.e6}, doi = {10.1016/j.cels.2020.05.006}, pmid = {32684275}, issn = {2405-4720}, mesh = {Data Analysis ; Humans ; Longitudinal Studies ; Microbiota/*physiology ; Research Design ; }, abstract = {The recently completed second phase of the Human Microbiome Project has highlighted the relationship between dynamic changes in the microbiome and disease, motivating new microbiome study designs based on longitudinal sampling. Yet, analysis of such data is hindered by presence of technical noise, high dimensionality, and data sparsity. Here, we introduce LUMINATE (longitudinal microbiome inference and zero detection), a fast and accurate method for inferring relative abundances from noisy read count data. We demonstrate that LUMINATE is orders of magnitude faster than current approaches, with better or similar accuracy. We further show that LUMINATE can accurately distinguish biological zeros, when a taxon is absent from the community, from technical zeros, when a taxon is below the detection threshold. We conclude by demonstrating the utility of LUMINATE on a real dataset, showing that LUMINATE smooths trajectories observed from noisy data. LUMINATE is freely available from https://github.com/tyjo/luminate.}, }
@article {pmid32660414, year = {2020}, author = {Huh, JW and Roh, TY}, title = {Opportunistic detection of Fusobacterium nucleatum as a marker for the early gut microbial dysbiosis.}, journal = {BMC microbiology}, volume = {20}, number = {1}, pages = {208}, pmid = {32660414}, issn = {1471-2180}, support = {NRF-2014M3C9A3064548, NRF-2017M3C9A6047625//National Research Foundation of Korea/International ; 10Z20130012243//Ministry of Education/International ; S2632274//Technology Development Program of MSS, Republic of Korea/International ; }, mesh = {Bacteria/*classification/isolation &amp; purification ; Discriminant Analysis ; Dysbiosis/*diagnosis ; Feces/microbiology ; Female ; Fusobacterium nucleatum/*isolation &amp; purification ; Gastrointestinal Microbiome ; Humans ; Inflammatory Bowel Diseases/*microbiology ; Logistic Models ; Longitudinal Studies ; Male ; Phylogeny ; }, abstract = {BACKGROUND: The essential roles of gut microbiome have been emphasized in modulating human health and disease. Fusobacterium nucleatum (F. nucleatum), an obligate Gram-negative microorganism residing in oral cavity, gastrointestinal tract and elsewhere, has been recently considered as a potential oncobacterium associated with human cancers. However, the consequence of its enrichment was not extensively explored in terms of microbial homeostasis and stability at the early stage of disease development.<br><br>RESULT: Our analysis on longitudinal metagenomic data generated by the Integrative Human Microbiome Project (iHMP) showed that F. nucleatum was frequently found in inflammatory bowel diseases (IBD) subjects with reduced microbial diversity. Using non-parametric logarithmic linear discriminant analysis (LDA) effect size (LEfSe) algorithm, 12 IBD- and 14 non-IBD-specific bacterial species were identified in the fecal metagenome and the IBD-specific ones were over-represented in the F. nucleatum-experienced subjects during long-term surveillance. In addition, F. nucleatum experience severely abrogated intra-personal stability of microbiome in IBD patients and induced highly variable gut microbiome between subjects. From the longitudinal comparison between microbial distributions prior and posterior to F. nucleatum detection, 41 species could be proposed as indicative "classifiers" for dysbiotic gut state. By multiple logistic regression models established on these classifiers, the high probability of experiencing F. nucleatum was significantly correlated with decreased alpha-diversity and increased number of biomarker species for IBD and colorectal cancer (CRC). Finally, microbial clustering confirmed that biomarker species for IBD and non-IBD conditions as well as CRC signature markers were well distinguishable and could be utilized for explaining gut symbiosis and dysbiosis.<br><br>CONCLUSION: F. nucleatum opportunistically appeared under early dysbiotic condition in gut, and discriminative classifier species associated with F. nucleatum were successfully applied to predict microbial alterations in both IBD and non-IBD conditions. Our prediction model and microbial classifier biomarkers for estimating gut dysbiosis should provide a novel aspect of microbial homeostasis/dynamics and useful information on non-invasive biomarker screening.}, }
@article {pmid32615913, year = {2020}, author = {Ames, NJ and Barb, JJ and Schuebel, K and Mudra, S and Meeks, BK and Tuason, RTS and Brooks, AT and Kazmi, N and Yang, S and Ratteree, K and Diazgranados, N and Krumlauf, M and Wallen, GR and Goldman, D}, title = {Longitudinal gut microbiome changes in alcohol use disorder are influenced by abstinence and drinking quantity.}, journal = {Gut microbes}, volume = {11}, number = {6}, pages = {1608-1631}, pmid = {32615913}, issn = {1949-0984}, support = {Z01 AA000280/ImNIH/Intramural NIH HHS/United States ; }, mesh = {Adult ; Alcohol Abstinence/psychology ; Alcohol Drinking/*metabolism/*psychology ; Ethanol/adverse effects/analysis/*metabolism ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*drug effects ; Humans ; Longitudinal Studies ; Male ; Microbiota/drug effects ; Middle Aged ; }, abstract = {Many patients with alcohol use disorder (AUD) consume alcohol chronically and in large amounts that alter intestinal microbiota, damage the gastrointestinal tract, and thereby injure other organs via malabsorption and intestinal inflammation. We hypothesized that alcohol consumption and subsequent abstinence would change the gut microbiome in adults admitted to a treatment program. Stool and oral specimens, diet data, gastrointestinal assessment scores, anxiety, depression measures and drinking amounts were collected longitudinally for up to 4 weeks in 22 newly abstinent inpatients with AUD who were dichotomized as less heavy drinkers (LHD, <10 drinks/d) and very heavy drinkers (VHD, 10 or more drinks/d). Next-generation 16 S rRNA gene sequencing was performed to measure the gut and oral microbiome at up to ten time points/subject and LHD and VHD were compared for change in principal components, Shannon diversity index and specific genera. The first three principal components explained 46.7% of the variance in gut microbiome diversity across time and all study subjects, indicating the change in gut microbiome following abstinence. The first time point was an outlier in three-dimensional principal component space versus all other time points. The gut microbiota in LHD and VHD were significantly dissimilar in change from day 1 to day 5 (p = .03) and from day 1 to week 3 (p = .02). The VHD drinking group displayed greater change from baseline. The Shannon diversity index of the gut microbiome changed significantly during abstinence in five participants. In both groups, the Shannon diversity was lower in the oral microbiome than gut. Ten total genera were shared between oral and stool in the AUD participants. These data were compared with healthy controls from the Human Microbiome Project to investigate the concept of a core microbiome. Rapid changes in gut microbiome following abstinence from alcohol suggest resilience of the gut microbiome in AUD and reflects the benefits of refraining from the highest levels of alcohol and potential benefits of abstinence.}, }
@article {pmid32563152, year = {2020}, author = {Hu, Y and Fang, L and Nicholson, C and Wang, K}, title = {Implications of Error-Prone Long-Read Whole-Genome Shotgun Sequencing on Characterizing Reference Microbiomes.}, journal = {iScience}, volume = {23}, number = {6}, pages = {101223}, pmid = {32563152}, issn = {2589-0042}, support = {R01 GM132713/GM/NIGMS NIH HHS/United States ; }, abstract = {Long-read sequencing techniques, such as the Oxford Nanopore Technology, can generate reads that are tens of kilobases in length and are therefore particularly relevant for microbiome studies. However, owing to the higher per-base error rates than typical short-read sequencing, the application of long-read sequencing on microbiomes remains largely unexplored. Here we deeply sequenced two human microbiota mock community samples (HM-276D and HM-277D) from the Human Microbiome Project. We showed that assembly programs consistently achieved high accuracy (∼99%) and completeness (∼99%) for bacterial strains with adequate coverage. We also found that long-read sequencing provides accurate estimates of species-level abundance (R = 0.94 for 20 bacteria with abundance ranging from 0.005% to 64%). Our results not only demonstrate the feasibility of characterizing complete microbial genomes and populations from error-prone Nanopore sequencing data but also highlight necessary bioinformatics improvements for future metagenomics tool development.}, }
@article {pmid32528054, year = {2020}, author = {Fukui, S and Morimoto, S and Ichinose, K and Nakashima, S and Ishimoto, H and Hara, A and Kakugawa, T and Sakamoto, N and Tsuji, Y and Aramaki, T and Koga, T and Kawashiri, SY and Iwamoto, N and Tamai, M and Nakamura, H and Origuchi, T and Ueki, Y and Suzuki, S and Mukae, H and Kawakami, A}, title = {Comparison of lung microbiota between antineutrophil cytoplasmic antibody-associated vasculitis and sarcoidosis.}, journal = {Scientific reports}, volume = {10}, number = {1}, pages = {9466}, pmid = {32528054}, issn = {2045-2322}, mesh = {Aged ; Aged, 80 and over ; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/immunology/*microbiology ; Antibodies, Antineutrophil Cytoplasmic/*immunology ; Bacteria/genetics/*immunology ; Bronchoalveolar Lavage Fluid/immunology/microbiology ; Female ; Humans ; Lung/*immunology/*microbiology ; Male ; Microbiota/genetics/*immunology ; Middle Aged ; RNA, Ribosomal, 16S/genetics ; Sarcoidosis/immunology/*microbiology ; }, abstract = {Microbial involvement in the pathogenesis have been suggested in both antineutrophil cytoplasmic antibody-associated vasculitis (AAV) and sarcoidosis, both of which have lung involvement. However, exhaustive research to assess the bacteria in the lung in AAV and in sarcoidosis have not been performed. We sought to elucidate the distinct dysbiotic lung microbiota between AAV and sarcoidosis. We used 16S rRNA gene high-throughput sequencing to obtain the bacterial community composition of bronchoalveolar lavage fluid (BALF) in patients with AAV (n = 16) compared to patients with sarcoidosis (n = 21). The patients had not undergone therapy with immunosuppressive medication when their BALF was acquired. No difference was observed in α-diversity between patients with AAV and patients with sarcoidosis when using all the detected taxa. We defined the taxa of the oral cavity by using the data of oral microbiota of healthy individuals from the Human Microbiome Project (HMP). The analysis using only oral taxa made the difference in α-diversity between AAV and sarcoidosis clearer compared with those using all the detected taxa. Besides, the analysis using detected taxa except for oral taxa also made the difference in α-diversity between AAV and sarcoidosis clearer compared with those using all the detected taxa. A linear negative relationship between the α-diversity and Birmingham vasculitis activity score (BVAS) was detected in the AAV group. The observed p-value for the effect of the disease groups on the ß-diversity was small while the effect of other factors including sex and smoking status did not have small p-values. By excluding oral taxa from all the detected taxa, we found a cluster mainly consisted of sarcoidosis patients which was characterized with microbial community monopolized by Erythrobacteraceae family. Our results suggested the importance of considering the influence of oral microbiota in evaluating lung microbiota.}, }
@article {pmid32518316, year = {2020}, author = {Chen, YR and Zheng, HM and Zhang, GX and Chen, FL and Chen, LD and Yang, ZC}, title = {High Oscillospira abundance indicates constipation and low BMI in the Guangdong Gut Microbiome Project.}, journal = {Scientific reports}, volume = {10}, number = {1}, pages = {9364}, pmid = {32518316}, issn = {2045-2322}, mesh = {*Body Mass Index ; China ; Clostridiales/*isolation &amp; purification/physiology ; Constipation/*microbiology ; Female ; *Gastrointestinal Microbiome ; Host-Pathogen Interactions ; Humans ; Male ; Middle Aged ; }, abstract = {Oscillospira is a common yet rarely cultivated gut bacterial genus. Recently human gut microbiota studies have demonstrated its underlying significance for host health. However, little is known about Oscillospira-related host information and the links between Oscillospira and other members of the gut microbial community. To study the ecology of Oscillospira and gain insights into Oscillospira-related host physiological conditions, we analyzed data from the Guangdong Gut Microbiome Project, one of the largest gut microbiota database currently. Data of 6376 participants were analyzed. We studied the prevalence and relative abundance of Oscillospira as well as the profiles of associated microbial communities. We found that Oscillospira is closely related to human health because its abundance was positively correlated with microbial diversity, high density lipoprotein, and sleep time, and was inversely correlated with diastolic blood pressure, systolic blood pressure, fasting blood glucose, triglyceride, uric acid and Bristol stool type. Moreover, random forest analysis with five-fold cross validation showed Oscillospira could be a predictor of low BMI and constipation in the subset. Overall, in this study, we provide a basic understanding of Oscillospira-related microbiota profile and physiological parameters of the host. Our results indicate Oscillospira may play a role in aggravating constipation.}, }
@article {pmid32515629, year = {2020}, author = {Voth, E and Khanna, S}, title = {The Integrative Human microbiome project: a mile stone in the understanding of the gut microbiome.}, journal = {Expert review of gastroenterology &amp; hepatology}, volume = {14}, number = {8}, pages = {639-642}, doi = {10.1080/17474124.2020.1780912}, pmid = {32515629}, issn = {1747-4132}, mesh = {Diabetes Mellitus/*microbiology ; Dysbiosis/complications ; Female ; Gastrointestinal Microbiome ; Host Microbial Interactions ; Humans ; Inflammatory Bowel Diseases/*microbiology ; Metabolomics ; Microbiota/*physiology ; National Institutes of Health (U.S.) ; Pregnancy ; Pregnancy Complications/microbiology ; United States ; }, }
@article {pmid32498714, year = {2020}, author = {Ma, B and Wang, Y and Ye, S and Liu, S and Stirling, E and Gilbert, JA and Faust, K and Knight, R and Jansson, JK and Cardona, C and Röttjers, L and Xu, J}, title = {Earth microbial co-occurrence network reveals interconnection pattern across microbiomes.}, journal = {Microbiome}, volume = {8}, number = {1}, pages = {82}, pmid = {32498714}, issn = {2049-2618}, mesh = {Animals ; *Bacteria/genetics ; Microbial Consortia ; *Microbiota ; Soil ; *Soil Microbiology ; }, abstract = {BACKGROUND: Microbial interactions shape the structure and function of microbial communities; microbial co-occurrence networks in specific environments have been widely developed to explore these complex systems, but their interconnection pattern across microbiomes in various environments at the global scale remains unexplored. Here, we have inferred an Earth microbial co-occurrence network from a communal catalog with 23,595 samples and 12,646 exact sequence variants from 14 environments in the Earth Microbiome Project dataset.<br><br>RESULTS: This non-random scale-free Earth microbial co-occurrence network consisted of 8 taxonomy distinct modules linked with different environments, which featured environment specific microbial co-occurrence relationships. Different topological features of subnetworks inferred from datasets trimmed into uniform size indicate distinct co-occurrence patterns in the microbiomes of various environments. The high number of specialist edges highlights that environmental specific co-occurrence relationships are essential features across microbiomes. The microbiomes of various environments were clustered into two groups, which were mainly bridged by the microbiomes of plant and animal surface. Acidobacteria Gp2 and Nisaea were identified as hubs in most of subnetworks. Negative edges proportions ranged from 1.9% in the soil subnetwork to 48.9% the non-saline surface subnetwork, suggesting various environments experience distinct intensities of competition or niche differentiation. Video abstract CONCLUSION: This investigation highlights the interconnection patterns across microbiomes in various environments and emphasizes the importance of understanding co-occurrence feature of microbiomes from a network perspective.}, }
@article {pmid32467266, year = {2020}, author = {Zhang, XL and Yang, X and Wang, SJ and Jiang, ZW and Xie, ZX and Zhang, L and Dai, J and Fan, CQ and Tian, XQ and Yang, Q}, title = {Draft Genome Sequences of Nine Cultivable Heterotrophic Proteobacteria Isolated from Phycosphere Microbiota of Toxic Alexandrium catenella LZT09.}, journal = {Microbiology resource announcements}, volume = {9}, number = {22}, pages = {}, pmid = {32467266}, issn = {2576-098X}, abstract = {Microscopic interactions between phycosphere microbiota and host algae play crucial roles in aquatic ecosystems. Despite their significance, there is a scarcity of available genome sequences derived from the phycosphere microbiome. Here, we report the draft genome sequences of nine heterotrophic proteobacterial strains isolated from the toxic dinoflagellate Alexandrium catenella LZT09 during execution of our Phycosphere Microbiome Project. Further exploration of the genomic features of the alga-associated bacterial community will profoundly help in deeply deciphering the processes and mechanisms governing the host-microbe interactome within algal holobionts in the ocean.}, }
@article {pmid32372951, year = {2020}, author = {Abdelsalam, NA and Ramadan, AT and ElRakaiby, MT and Aziz, RK}, title = {Toxicomicrobiomics: The Human Microbiome vs. Pharmaceutical, Dietary, and Environmental Xenobiotics.}, journal = {Frontiers in pharmacology}, volume = {11}, number = {}, pages = {390}, pmid = {32372951}, issn = {1663-9812}, abstract = {The harmful impact of xenobiotics on the environment and human health is being more widely recognized; yet, inter- and intraindividual genetic variations among humans modulate the extent of harm, mostly through modulating the outcome of xenobiotic metabolism and detoxification. As the Human Genome Project revealed that host genetic, epigenetic, and regulatory variations could not sufficiently explain the complexity of interindividual variability in xenobiotics metabolism, its sequel, the Human Microbiome Project, is investigating how this variability may be influenced by human-associated microbial communities. Xenobiotic-microbiome relationships are mutual and dynamic. Not only does the human microbiome have a direct metabolizing potential on xenobiotics, but it can also influence the expression of the host metabolizing genes and the activity of host enzymes. On the other hand, xenobiotics may alter the microbiome composition, leading to a state of dysbiosis, which is linked to multiple diseases and adverse health outcomes, including increased toxicity of some xenobiotics. Toxicomicrobiomics studies these mutual influences between the ever-changing microbiome cloud and xenobiotics of various origins, with emphasis on their fate and toxicity, as well the various classes of microbial xenobiotic-modifying enzymes. This review article discusses classic and recent findings in toxicomicrobiomics, with examples of interactions between gut, skin, urogenital, and oral microbiomes with pharmaceutical, food-derived, and environmental xenobiotics. The current state and future prospects of toxicomicrobiomic research are discussed, and the tools and strategies for performing such studies are thoroughly and critically compared.}, }
@article {pmid32369899, year = {2020}, author = {Lee-Sarwar, KA and Lasky-Su, J and Kelly, RS and Litonjua, AA and Weiss, ST}, title = {Metabolome-Microbiome Crosstalk and Human Disease.}, journal = {Metabolites}, volume = {10}, number = {5}, pages = {}, pmid = {32369899}, issn = {2218-1989}, support = {R01HL141826/NH/NIH HHS/United States ; R01 DK125273/DK/NIDDK NIH HHS/United States ; K08 HL148178/NH/NIH HHS/United States ; R01 HL123915/HL/NHLBI NIH HHS/United States ; R01 HL155742/HL/NHLBI NIH HHS/United States ; R01 HL141826/HL/NHLBI NIH HHS/United States ; UH3OD023268/NH/NIH HHS/United States ; K08 HL148178/HL/NHLBI NIH HHS/United States ; R01HL123915/NH/NIH HHS/United States ; K01 HL146980/NH/NIH HHS/United States ; UH3 OD023268/OD/NIH HHS/United States ; K01 HL146980/HL/NHLBI NIH HHS/United States ; }, abstract = {In this review, we discuss the growing literature demonstrating robust and pervasive associations between the microbiome and metabolome. We focus on the gut microbiome, which harbors the taxonomically most diverse and the largest collection of microorganisms in the human body. Methods for integrative analysis of these "omics" are under active investigation and we discuss the advances and challenges in the combined use of metabolomics and microbiome data. Findings from large consortia, including the Human Microbiome Project and Metagenomics of the Human Intestinal Tract (MetaHIT) and others demonstrate the impact of microbiome-metabolome interactions on human health. Mechanisms whereby the microbes residing in the human body interact with metabolites to impact disease risk are beginning to be elucidated, and discoveries in this area will likely be harnessed to develop preventive and treatment strategies for complex diseases.}, }
@article {pmid32366680, year = {2020}, author = {Zhou, X and Johnson, JS and Spakowicz, D and Zhou, W and Zhou, Y and Sodergren, E and Snyder, M and Weinstock, GM}, title = {Longitudinal Analysis of Serum Cytokine Levels and Gut Microbial Abundance Links IL-17/IL-22 With Clostridia and Insulin Sensitivity in Humans.}, journal = {Diabetes}, volume = {69}, number = {8}, pages = {1833-1842}, pmid = {32366680}, issn = {1939-327X}, support = {P30 CA034196/CA/NCI NIH HHS/United States ; P30 DK116074/DK/NIDDK NIH HHS/United States ; }, mesh = {Bayes Theorem ; Firmicutes/physiology ; Gastrointestinal Microbiome/*physiology ; Humans ; Interleukin-17/*blood ; Interleukins/*blood ; Longitudinal Studies ; Microbiota/physiology ; Prediabetic State/immunology/microbiology ; Interleukin-22 ; }, abstract = {Recent studies using mouse models suggest that interaction between the gut microbiome and IL-17/IL-22-producing cells plays a role in the development of metabolic diseases. We investigated this relationship in humans using data from the prediabetes study of the Integrated Human Microbiome Project (iHMP). Specifically, we addressed the hypothesis that early in the onset of metabolic diseases there is a decline in serum levels of IL-17/IL-22, with concomitant changes in the gut microbiome. Clustering iHMP study participants on the basis of longitudinal IL-17/IL-22 profiles identified discrete groups. Individuals distinguished by low levels of IL-17/IL-22 were linked to established markers of metabolic disease, including insulin sensitivity. These individuals also displayed gut microbiome dysbiosis, characterized by decreased diversity, and IL-17/IL-22-related declines in the phylum Firmicutes, class Clostridia, and order Clostridiales This ancillary analysis of the iHMP data therefore supports a link between the gut microbiome, IL-17/IL-22, and the onset of metabolic diseases. This raises the possibility for novel, microbiome-related therapeutic targets that may effectively alleviate metabolic diseases in humans as they do in animal models.}, }
@article {pmid32332073, year = {2020}, author = {Manasson, J and Blank, RB and Scher, JU}, title = {The microbiome in rheumatology: Where are we and where should we go?.}, journal = {Annals of the rheumatic diseases}, volume = {79}, number = {6}, pages = {727-733}, doi = {10.1136/annrheumdis-2019-216631}, pmid = {32332073}, issn = {1468-2060}, support = {R01 AR074500/AR/NIAMS NIH HHS/United States ; }, mesh = {Autoimmune Diseases/drug therapy/*microbiology ; Biomedical Research ; Humans ; *Microbiota ; Rheumatic Diseases/drug therapy/*microbiology ; }, abstract = {From birth, humans coexist and coevolve with trillions of micro-organisms inhabiting most body surfaces and cavities, referred to as the human microbiome. Advances in sequencing technologies and computational methods have propelled the exploration of the microbiome's contribution to human health and disease, spearheaded by massive efforts such as the Human Microbiome Project and the Europe-based MetaHit Consortium. Yet, despite the accumulated body of literature and a growing awareness among patients, microbiome research in rheumatology has not had a key impact on clinical practice. Herein, we describe some of the landmark microbiome studies in autoimmunity and rheumatology, the challenges and opportunities of microbiome research and how to navigate them, advances in related fields that have overcome these pitfalls, and future directions of harnessing the microbiome for diagnostic and therapeutic purposes.}, }
@article {pmid32299880, year = {2020}, author = {Yang, X and Jiang, ZW and Chen, Z and Dai, J and Wang, L and Zhang, XL and Yang, Q}, title = {Complete Genome Sequence of a Toxic and Bioactive Exopolysaccharide-Bearing Bacterium, Sulfitobacter sp. Strain AM1-D1.}, journal = {Microbiology resource announcements}, volume = {9}, number = {16}, pages = {}, pmid = {32299880}, issn = {2576-098X}, abstract = {Sulfitobacter sp. strain AM1-D1, a toxic bacterium of the family Rhodobacteraceae, was isolated from the cultivable phycosphere microbiota of marine toxigenic dinoflagellate Alexandrium minutum amtk4. The complete 4.69-Mb genome comprises one single circular chromosome and five circular plasmids. It has 4,559 coding genes, including those for biosynthesis or degradation of saxitoxin and bioactive exopolysaccharides.}, }
@article {pmid32279227, year = {2020}, author = {Rinaldi, F and Trink, A and Pinto, D}, title = {Efficacy of Postbiotics in a PRP-Like Cosmetic Product for the Treatment of Alopecia Area Celsi: A Randomized Double-Blinded Parallel-Group Study.}, journal = {Dermatology and therapy}, volume = {10}, number = {3}, pages = {483-493}, pmid = {32279227}, issn = {2193-8210}, abstract = {INTRODUCTION: Alopecia areata (AA), also known as 'area Celsi', is the second most common form of hair loss affecting the scalp. Newly proposed treatments for AA include low-level light therapy, biologics such as Janus kinase inhibitors and autologous platelet-rich plasma (PRP), which is a well-known "elixir" for hair growth. Bioactive peptides developed through biotechnological applications have been used to overcome the limitations of PRP. More recently, the involvement of microbiota in hair growth disorders, in AA in particular, has been reported, and the usefulness of microbial metabolites, i.e. postbiotics, has been suggested.<br><br>METHODS: This study was a randomized double-blinded parallel-group study in which 160 persons of both sexes affected by AA and aged between 18 and 60&#xa0;years were enrolled. The subjects were randomly assigned to a treatment group (group 1), receiving the TR-PRP plus-Celsi cosmetic product, and a placebo group (group 2). The SALT (Severity of Alopecia Tool) score was determined in both groups at baseline and after 2 and 3&#xa0;months of treatment, and the results compared between groups.<br><br>RESULTS: The subjects in group 1 showed a significant change from baseline in SALT score at 2&#xa0;months of treatment (61.04%&#x2009;&#xb1;&#x2009;3.45%; p&#x2009;<&#x2009;0.0001), with a further improvement at the end of treatment (3 months) (69.56%&#x2009;&#xb1;&#x2009;4.32%; p&#x2009;<&#x2009;0.0001). No significant changes from baseline were reported for the subjects in group 2 (T1: 26.45%&#x2009;&#xb1;&#x2009;3.64%; T3: 27.63%&#x2009;&#xb1;&#x2009;7.61%).<br><br>CONCLUSIONS: The results of this study provide further proof of the efficacy of bioactive peptides that mimick the growth factors present in PRP in subjects affected by AA. They also add to our knowledge of the link between microbiota and hair growth disorders, emphasizing the importance of studies on the microbial community and microbial metabolites as a novel therapeutic approach.}, }
@article {pmid32247371, year = {2020}, author = {Keshavarzian, A and Engen, P and Bonvegna, S and Cilia, R}, title = {The gut microbiome in Parkinson's disease: A culprit or a bystander?.}, journal = {Progress in brain research}, volume = {252}, number = {}, pages = {357-450}, doi = {10.1016/bs.pbr.2020.01.004}, pmid = {32247371}, issn = {1875-7855}, mesh = {Animals ; Dopamine Agents/*pharmacology ; *Dysbiosis/immunology/metabolism/microbiology ; *Gastrointestinal Microbiome/immunology ; Humans ; *Inflammation/immunology/metabolism/microbiology ; *Life Style ; *Parkinson Disease/drug therapy/immunology/metabolism/microbiology ; *alpha-Synuclein/metabolism ; }, abstract = {In recent years, large-scale metagenomics projects such as the Human Microbiome Project placed the gut microbiota under the spotlight of research on its role in health and in the pathogenesis several diseases, as it can be a target for novel therapeutical approaches. The emerging concept of a microbiota modulation of the gut-brain axis in the pathogenesis of neurodegenerative disorders has been explored in several studies in animal models, as well as in human subjects. Particularly, research on changes in the composition of gut microbiota as a potential trigger for alpha-synuclein (α-syn) pathology in Parkinson's disease (PD) has gained increasing interest. In the present review, we first provide the basis to the understanding of the role of gut microbiota in healthy subjects and the molecular basis of the gut-brain interaction, focusing on metabolic and neuroinflammatory factors that could trigger the alpha-synuclein conformational changes and aggregation. Then, we critically explored preclinical and clinical studies reporting on the changes in gut microbiota in PD, as compared to healthy subjects. Furthermore, we examined the relationship between the gut microbiota and PD clinical features, discussing data consistently reported across studies, as well as the potential sources of inconsistencies. As a further step toward understanding the effects of gut microbiota on PD, we discussed the relationship between dysbiosis and response to dopamine replacement therapy, focusing on Levodopa metabolism. We conclude that further studies are needed to determine whether the gut microbiota changes observed so far in PD patients is the cause or, instead, it is merely a consequence of lifestyle changes associated with the disease. Regardless, studies so far strongly suggest that changes in microbiota appears to be impactful in pathogenesis of neuroinflammation. Thus, dysbiotic microbiota in PD could influence the disease course and response to medication, especially Levodopa. Future research will assess the impact of microbiota-directed therapeutic intervention in PD patients.}, }
@article {pmid32239603, year = {2020}, author = {Bruessow, F and Brüssow, H}, title = {Our extended genotype-An argument for the study of domesticated microbes.}, journal = {Environmental microbiology}, volume = {22}, number = {5}, pages = {1669-1674}, doi = {10.1111/1462-2920.15001}, pmid = {32239603}, issn = {1462-2920}, mesh = {Animals ; Bacteria/*classification/*genetics ; Fermentation ; Fermented Foods/*microbiology ; Food Microbiology/*methods ; Genotype ; Humans ; Microbiota/genetics ; }, abstract = {We interpret the domesticated organisms-plants, animals, and the domesticated microbes used for food fermentation-as an extended genotype of humans due to their close relationship with our species. We propose to analyse the role of microbes in traditionally fermented food with the approaches used in the human microbiome project, and we expect to find associations with ethnic groups, explaining part of human (culinary) culture.}, }
@article {pmid32238913, year = {2020}, author = {Greene, LK and Williams, CV and Junge, RE and Mahefarisoa, KL and Rajaonarivelo, T and Rakotondrainibe, H and O'Connell, TM and Drea, CM}, title = {A role for gut microbiota in host niche differentiation.}, journal = {The ISME journal}, volume = {14}, number = {7}, pages = {1675-1687}, pmid = {32238913}, issn = {1751-7370}, mesh = {Feces ; *Gastrointestinal Microbiome ; Gastrointestinal Tract ; Metagenome ; *Microbiota ; }, abstract = {If gut microbes influence host behavioral ecology in the short term, over evolutionary time, they could drive host niche differentiation. We explored this possibility by comparing the gut microbiota of Madagascar's folivorous lemurs from Indriidae and Lepilemuridae. Occurring sympatrically in the eastern rainforest, our four, target species have different dietary specializations, including frugo-folivory (sifakas), young-leaf folivory (indri and woolly lemurs), and mature-leaf folivory (sportive lemurs). We collected fecal samples, from 2013 to 2017, and used amplicon sequencing, metagenomic sequencing, and nuclear magnetic resonance spectroscopy, respectively, to integrate analyses of gut microbiome structure and function with analysis of the colonic metabolome. The lemurs harbored species-specific microbiomes, metagenomes, and metabolomes that were tuned to their dietary specializations: Frugo-folivores had greater microbial and metagenomic diversity, and harbored generalist taxa. Mature-leaf folivores had greater individual microbiome variation, and taxa and metabolites putatively involved in cellulolysis. The consortia even differed between related, young-leaf specialists, with indri prioritizing metabolism of fiber and plant secondary compounds, and woolly lemurs prioritizing amino-acid cycling. Specialized gut microbiota and associated gastrointestinal morphologies enable folivores to variably tolerate resource fluctuation and support nutrient extraction from challenging resources (e.g., by metabolizing plant secondary compounds or recalcitrant fibers), perhaps ultimately facilitating host species' diversity and specialized feeding ecologies.}, }
@article {pmid32231664, year = {2020}, author = {Al-Nasiry, S and Ambrosino, E and Schlaepfer, M and Morré, SA and Wieten, L and Voncken, JW and Spinelli, M and Mueller, M and Kramer, BW}, title = {The Interplay Between Reproductive Tract Microbiota and Immunological System in Human Reproduction.}, journal = {Frontiers in immunology}, volume = {11}, number = {}, pages = {378}, pmid = {32231664}, issn = {1664-3224}, mesh = {Dysbiosis/immunology ; Female ; Genitalia, Female/*immunology/*microbiology ; Host Microbial Interactions/*immunology ; Humans ; *Microbiota ; Pregnancy/*immunology ; Pregnancy Complications/immunology/microbiology ; }, abstract = {In the last decade, the microbiota, i.e., combined populations of microorganisms living inside and on the surface of the human body, has increasingly attracted attention of researchers in the medical field. Indeed, since the completion of the Human Microbiome Project, insight and interest in the role of microbiota in health and disease, also through study of its combined genomes, the microbiome, has been steadily expanding. One less explored field of microbiome research has been the female reproductive tract. Research mainly from the past decade suggests that microbial communities residing in the reproductive tract represent a large proportion of the female microbial network and appear to be involved in reproductive failure and pregnancy complications. Microbiome research is facing technological and methodological challenges, as detection techniques and analysis methods are far from being standardized. A further hurdle is understanding the complex host-microbiota interaction and the confounding effect of a multitude of constitutional and environmental factors. A key regulator of this interaction is the maternal immune system that, during the peri-conceptional stage and even more so during pregnancy, undergoes considerable modulation. This review aims to summarize the current literature on reproductive tract microbiota describing the composition of microbiota in different anatomical locations (vagina, cervix, endometrium, and placenta). We also discuss putative mechanisms of interaction between such microbial communities and various aspects of the immune system, with a focus on the characteristic immunological changes during normal pregnancy. Furthermore, we discuss how abnormal microbiota composition, "dysbiosis," is linked to a spectrum of clinical disorders related to the female reproductive system and how the maternal immune system is involved. Finally, based on the data presented in this review, the future perspectives in diagnostic approaches, research directions and therapeutic opportunities are explored.}, }
@article {pmid32214244, year = {2020}, author = {Poore, GD and Kopylova, E and Zhu, Q and Carpenter, C and Fraraccio, S and Wandro, S and Kosciolek, T and Janssen, S and Metcalf, J and Song, SJ and Kanbar, J and Miller-Montgomery, S and Heaton, R and Mckay, R and Patel, SP and Swafford, AD and Knight, R}, title = {Microbiome analyses of blood and tissues suggest cancer diagnostic approach.}, journal = {Nature}, volume = {579}, number = {7800}, pages = {567-574}, pmid = {32214244}, issn = {1476-4687}, support = {P50 DA026306/DA/NIDA NIH HHS/United States ; HHSN261201500003C/CA/NCI NIH HHS/United States ; HHSN261201400008C/CA/NCI NIH HHS/United States ; P30 CA023100/CA/NCI NIH HHS/United States ; HHSN261201500003I/CA/NCI NIH HHS/United States ; T32 GM007198/GM/NIGMS NIH HHS/United States ; F30 CA243480/CA/NCI NIH HHS/United States ; R01 DA026334/DA/NIDA NIH HHS/United States ; P01 DA012065/DA/NIDA NIH HHS/United States ; R00 AA020235/AA/NIAAA NIH HHS/United States ; P30 MH062512/MH/NIMH NIH HHS/United States ; }, mesh = {Case-Control Studies ; Cohort Studies ; DNA, Bacterial/blood ; DNA, Viral/blood ; Datasets as Topic ; Female ; Humans ; Liquid Biopsy ; Lung Neoplasms/blood/diagnosis/microbiology ; Male ; Melanoma/blood/diagnosis/microbiology ; Microbiota/*genetics ; Neoplasms/blood/*diagnosis/*microbiology ; Plasma/*microbiology ; Prostatic Neoplasms/blood/diagnosis/microbiology ; Reproducibility of Results ; }, abstract = {Systematic characterization of the cancer microbiome provides the opportunity to develop techniques that exploit non-human, microorganism-derived molecules in the diagnosis of a major human disease. Following recent demonstrations that some types of cancer show substantial microbial contributions[1-10], we re-examined whole-genome and whole-transcriptome sequencing studies in The Cancer Genome Atlas[11] (TCGA) of 33 types of cancer from treatment-naive patients (a total of 18,116 samples) for microbial reads, and found unique microbial signatures in tissue and blood within and between most major types of cancer. These TCGA blood signatures remained predictive when applied to patients with stage Ia-IIc cancer and cancers lacking any genomic alterations currently measured on two commercial-grade cell-free tumour DNA platforms, despite the use of very stringent decontamination analyses that discarded up to 92.3% of total sequence data. In addition, we could discriminate among samples from healthy, cancer-free individuals (n = 69) and those from patients with multiple types of cancer (prostate, lung, and melanoma; 100 samples in total) solely using plasma-derived, cell-free microbial nucleic acids. This potential microbiome-based oncology diagnostic tool warrants further exploration.}, }
@article {pmid32191789, year = {2020}, author = {Falcon, T and Foletto, KC and Siebert, M and Pinto, DE and Andrades, M and Bertoluci, MC}, title = {Metabarcoding reveals that a non-nutritive sweetener and sucrose yield similar gut microbiota patterns in Wistar rats.}, journal = {Genetics and molecular biology}, volume = {43}, number = {1}, pages = {e20190028}, pmid = {32191789}, issn = {1415-4757}, abstract = {The effects of non-nutritive sweeteners (NNS) on the gut microbiota are an area of increasing research interest due to their potential influence on weight gain, insulin resistance, and inflammation. Studies have shown that mice and rats fed saccharin develop weight gain and metabolic alterations, possibly related to changes in gut microbiota. Here, we hypothesized that chronic exposure to a commercial NNS would change the gut microbiota composition in Wistar rats when compared to sucrose exposure. To test this hypothesis, Wistar rats were fed either NNS- or sucrose-supplemented yogurt for 17 weeks alongside standard chow (ad libitum). The gut microbiome was assessed by 16S rDNA deep sequencing. Assembly and quantification were conducted using the Brazilian Microbiome Project pipeline for Ion Torrent data with modifications. Statistical analyses were performed in the R software environment. We found that chronic feeding of a commercial NNS-sweetened yogurt to Wistar rats, within the recommended dose range, did not significantly modify gut microbiota composition in comparison to sucrose-sweetened yogurt. Our findings do not support the hypothesis that moderate exposure to NNS is associated with changes in gut microbiota pattern compared to sucrose, at least in this experimental model.}, }
@article {pmid32156071, year = {2020}, author = {Pan, S and Hullar, MAJ and Lai, LA and Peng, H and May, DH and Noble, WS and Raftery, D and Navarro, SL and Neuhouser, ML and Lampe, PD and Lampe, JW and Chen, R}, title = {Gut Microbial Protein Expression in Response to Dietary Patterns in a Controlled Feeding Study: A Metaproteomic Approach.}, journal = {Microorganisms}, volume = {8}, number = {3}, pages = {}, pmid = {32156071}, issn = {2076-2607}, support = {R01 CA192222/NH/NIH HHS/United States ; P30 CA015704/CA/NCI NIH HHS/United States ; U54 CA116847/NH/NIH HHS/United States ; R01 CA211892/CA/NCI NIH HHS/United States ; R01 CA192222/CA/NCI NIH HHS/United States ; R01 CA211892/NH/NIH HHS/United States ; P30 CA015704/NH/NIH HHS/United States ; }, abstract = {Although the gut microbiome has been associated with dietary patterns linked to health, microbial metabolism is not well characterized. This ancillary study was a proof of principle analysis for a novel application of metaproteomics to study microbial protein expression in a controlled dietary intervention. We measured the response of the microbiome to diet in a randomized crossover dietary intervention of a whole-grain, low glycemic load diet (WG) and a refined-grain, high glycemic load diet (RG). Total proteins in stools from 9 participants at the end of each diet period (n = 18) were analyzed by LC MS/MS and proteins were identified using the Human Microbiome Project (HMP) human gut microbiome database and UniProt human protein databases. T-tests, controlling for false discovery rate (FDR) <10%, were used to compare the Gene Ontology (GO) biological processes and bacterial enzymes between the two interventions. Using shotgun proteomics, more than 53,000 unique peptides were identified including microbial (89%) and human peptides (11%). Forty-eight bacterial enzymes were statistically different between the diets, including those implicated in SCFA production and degradation of fatty acids. Enzymes associated with degradation of human mucin were significantly enriched in the RG diet. These results illustrate that the metaproteomic approach is a valuable tool to study the microbial metabolism of diets that may influence host health.}, }
@article {pmid32129192, year = {2020}, author = {Vairakkani, R and Fernando, ME and Raj, TY}, title = {Metabolome and microbiome in kidney diseases.}, journal = {Saudi journal of kidney diseases and transplantation : an official publication of the Saudi Center for Organ Transplantation, Saudi Arabia}, volume = {31}, number = {1}, pages = {1-9}, doi = {10.4103/1319-2442.279927}, pmid = {32129192}, issn = {1319-2442}, mesh = {*Gastrointestinal Microbiome ; Humans ; *Kidney Diseases/metabolism/microbiology/physiopathology/therapy ; *Metabolome ; }, abstract = {Despite several decades of intensive research and hard work in nephrology, a void exists in the availability of markers for identifying at-risk individuals, diagnosing diseases at incipient stage, and predicting treatment response. Most of the current widely available diagnostic tools such as creatinine, urine analysis, and imaging studies are quite insensitive such that about half of the kidney function is lost before perceivable changes are observed with these tests. In addition, these parameters are affected by factors other than renal, questioning their specificity. Renal biopsy, though specific, is quite expensive, risky, and invasive. The recent surge in the knowledge of small molecules in the tissue and body fluids, "metabolomics," thanks to the Human Metabolome Database created by the Human Metabolome Project, has opened a new avenue for better understanding the disease pathogenesis and, in parallel, to identify novel biomarkers and druggable targets. Kidney, by virtue of its metabolic machinery and also being a major handler of metabolites generated by other tissues, is very much amenable to the metabolomic approach of studying its various perturbations. The gut microbiome, characterized by the Human Microbiome Project, is one of the principal players in metabolomics. Changes in metabolite profile due to alterations in gut microbiome can occur either as a cause or consequence of renal diseases. Unmasking the renal-metabolome-microbiome link has a great potential to script a new era in the diagnosis and management of renal diseases.}, }
@article {pmid32098835, year = {2020}, author = {Rosa, BA and Mihindukulasuriya, K and Hallsworth-Pepin, K and Wollam, A and Martin, J and Snowden, C and Dunne, WM and Weinstock, GM and Burnham, CA and Mitreva, M}, title = {Improving Characterization of Understudied Human Microbiomes Using Targeted Phylogenetics.}, journal = {mSystems}, volume = {5}, number = {1}, pages = {}, pmid = {32098835}, issn = {2379-5077}, support = {U54 HG004968/HG/NHGRI NIH HHS/United States ; }, abstract = {Whole-genome bacterial sequences are required to better understand microbial functions, niche-specific bacterial metabolism, and disease states. Although genomic sequences are available for many of the human-associated bacteria from commonly tested body habitats (e.g., feces), as few as 13% of bacterium-derived reads from other sites such as the skin map to known bacterial genomes. To facilitate a better characterization of metagenomic shotgun reads from underrepresented body sites, we collected over 10,000 bacterial isolates originating from 14 human body habitats, identified novel taxonomic groups based on full-length 16S rRNA gene sequences, clustered the sequences to ensure that no individual taxonomic group was overselected for sequencing, prioritized bacteria from underrepresented body sites (such as skin and respiratory and urinary tracts), and sequenced and assembled genomes for 665 new bacterial strains. Here, we show that addition of these genomes improved read mapping rates of Human Microbiome Project (HMP) metagenomic samples by nearly 30% for the previously underrepresented phylum Fusobacteria, and 27.5% of the novel genomes generated here had high representation in at least one of the tested HMP samples, compared to 12.5% of the sequences in the public databases, indicating an enrichment of useful novel genomic sequences resulting from the prioritization procedure. As our understanding of the human microbiome continues to improve and to enter the realm of therapy developments, targeted approaches such as this to improve genomic databases will increase in importance from both an academic and a clinical perspective.IMPORTANCE The human microbiome plays a critically important role in health and disease, but current understanding of the mechanisms underlying the interactions between the varying microbiome and the different host environments is lacking. Having access to a database of fully sequenced bacterial genomes provides invaluable insights into microbial functions, but currently sequenced genomes for the human microbiome have largely come from a limited number of body sites (primarily feces), while other sites such as the skin, respiratory tract, and urinary tract are underrepresented, resulting in as little as 13% of bacterium-derived reads mapping to known bacterial genomes. Here, we sequenced and assembled 665 new bacterial genomes, prioritized from a larger database to select underrepresented body sites and bacterial taxa in the existing databases. As a result, we substantially improve mapping rates for samples from the Human Microbiome Project and provide an important contribution to human bacterial genomic databases for future studies.}, }
@article {pmid32094388, year = {2020}, author = {Marsland, R and Cui, W and Mehta, P}, title = {A minimal model for microbial biodiversity can reproduce experimentally observed ecological patterns.}, journal = {Scientific reports}, volume = {10}, number = {1}, pages = {3308}, pmid = {32094388}, issn = {2045-2322}, support = {R35 GM119461/GM/NIGMS NIH HHS/United States ; }, mesh = {Bacteria/classification/metabolism ; *Biodiversity ; Humans ; Microbiota ; *Models, Biological ; Principal Component Analysis ; }, abstract = {Surveys of microbial biodiversity such as the Earth Microbiome Project (EMP) and the Human Microbiome Project (HMP) have revealed robust ecological patterns across different environments. A major goal in ecology is to leverage these patterns to identify the ecological processes shaping microbial ecosystems. One promising approach is to use minimal models that can relate mechanistic assumptions at the microbe scale to community-level patterns. Here, we demonstrate the utility of this approach by showing that the Microbial Consumer Resource Model (MiCRM) - a minimal model for microbial communities with resource competition, metabolic crossfeeding and stochastic colonization - can qualitatively reproduce patterns found in survey data including compositional gradients, dissimilarity/overlap correlations, richness/harshness correlations, and nestedness of community composition. By using the MiCRM to generate synthetic data with different environmental and taxonomical structure, we show that large scale patterns in the EMP can be reproduced by considering the energetic cost of surviving in harsh environments and HMP patterns may reflect the importance of environmental filtering in shaping competition. We also show that recently discovered dissimilarity-overlap correlations in the HMP likely arise from communities that share similar environments rather than reflecting universal dynamics. We identify ecologically meaningful changes in parameters that alter or destroy each one of these patterns, suggesting new mechanistic hypotheses for further investigation. These findings highlight the promise of minimal models for microbial ecology.}, }
@article {pmid32047925, year = {2020}, author = {Ordiz, MI and Janssen, S and Humphrey, G and Ackermann, G and Stephenson, K and Agapova, S and Divala, O and Kaimila, Y and Maleta, K and Zhong, C and Knight, R and Trehan, I and Tarr, PI and Rusconi, B and Manary, MJ}, title = {The effect of legume supplementation on the gut microbiota in rural Malawian infants aged 6 to 12 months.}, journal = {The American journal of clinical nutrition}, volume = {111}, number = {4}, pages = {884-892}, pmid = {32047925}, issn = {1938-3207}, mesh = {Bacteria/classification/genetics/isolation &amp; purification ; Breast Feeding ; Double-Blind Method ; Fabaceae/*metabolism ; Feces/microbiology ; Female ; *Gastrointestinal Microbiome ; Humans ; Infant ; Infant Nutritional Physiological Phenomena ; Intestines/growth &amp; development/microbiology ; Malawi ; Male ; Rural Population/statistics &amp; numerical data ; }, abstract = {BACKGROUND: Common bean and cowpea contain about 25% protein and 25% fiber, and are recommended as complementary foods in sub-Saharan Africa.<br><br>OBJECTIVE: The objective of this study was to determine if a daily legume supplement given to Malawian infants aged 6 to 12 mo alters the 16S configuration of the fecal microbiota as read out by amplicon sequence variants (ASVs).<br><br>METHODS: This study was conducted within the context of a randomized, double-blind, controlled clinical trial to assess whether cowpea or common bean supplementation reduced intestinal permeability or increased linear growth. There were 2 village clusters in which the study was conducted. Fresh stool collections were flash frozen from 236 infants at &#x2264;6 time points. The stools were sequenced using Earth Microbiome project protocols and data were processed using Qiime and Qiita, open-source, validated software packages. &#x3b1;-diversity was measured using the Faith's test. The 16S configuration was characterized by determining the weighted UniFrac distances of the ASVs and comparing them using permutational multivariate ANOVA.<br><br>RESULTS: Among the 1249 samples analyzed, the &#x3b1;-diversity of the fecal microbiome was unchanged among subjects after initiation of legume supplementation. Neither cowpea nor common bean altered the overall 16S configuration at any age. The 16S configuration differed between children with adequate and poor linear growth aged from 6 to 9&#xa0;mo, but no specific ASVs differed in relative abundance. The 16S configuration differed between children with normal and abnormal intestinal permeability at 9&#xa0;mo, but no specific ASVs differed in relative abundance. Among categorical characteristics of the population associated with different 16S configurations, village cluster was most pronounced.<br><br>CONCLUSION: Legume supplementation in breastfed, rural African infants did not affect the structure of the gut microbial communities until the children were aged 9&#xa0;mo. This trial was registered at clinicaltrials.gov as NCT02472262.}, }
@article {pmid32023941, year = {2020}, author = {Chowdhury, S and Fong, SS}, title = {Computational Modeling of the Human Microbiome.}, journal = {Microorganisms}, volume = {8}, number = {2}, pages = {}, pmid = {32023941}, issn = {2076-2607}, support = {U54HD080784//Office of Extramural Research, National Institutes of Health/ ; }, abstract = {The impact of microorganisms on human health has long been acknowledged and studied, but recent advances in research methodologies have enabled a new systems-level perspective on the collections of microorganisms associated with humans, the human microbiome. Large-scale collaborative efforts such as the NIH Human Microbiome Project have sought to kick-start research on the human microbiome by providing foundational information on microbial composition based upon specific sites across the human body. Here, we focus on the four main anatomical sites of the human microbiome: gut, oral, skin, and vaginal, and provide information on site-specific background, experimental data, and computational modeling. Each of the site-specific microbiomes has unique organisms and phenomena associated with them; there are also high-level commonalities. By providing an overview of different human microbiome sites, we hope to provide a perspective where detailed, site-specific research is needed to understand causal phenomena that impact human health, but there is equally a need for more generalized methodology improvements that would benefit all human microbiome research.}, }
@article {pmid32014020, year = {2020}, author = {Woodhams, DC and Bletz, MC and Becker, CG and Bender, HA and Buitrago-Rosas, D and Diebboll, H and Huynh, R and Kearns, PJ and Kueneman, J and Kurosawa, E and LaBumbard, BC and Lyons, C and McNally, K and Schliep, K and Shankar, N and Tokash-Peters, AG and Vences, M and Whetstone, R}, title = {Host-associated microbiomes are predicted by immune system complexity and climate.}, journal = {Genome biology}, volume = {21}, number = {1}, pages = {23}, pmid = {32014020}, issn = {1474-760X}, mesh = {Adaptation, Physiological ; Animals ; *Climate ; Host-Pathogen Interactions/*immunology ; Humans ; *Microbiota ; }, abstract = {BACKGROUND: Host-associated microbiomes, the microorganisms occurring inside and on host surfaces, influence evolutionary, immunological, and ecological processes. Interactions between host and microbiome affect metabolism and contribute to host adaptation to changing environments. Meta-analyses of host-associated bacterial communities have the potential to elucidate global-scale patterns of microbial community structure and function. It is possible that host surface-associated (external) microbiomes respond more strongly to variations in environmental factors, whereas internal microbiomes are more tightly linked to host factors.<br><br>RESULTS: Here, we use the dataset from the Earth Microbiome Project and accumulate data from 50 additional studies totaling 654 host species and over 15,000 samples to examine global-scale patterns of bacterial diversity and function. We analyze microbiomes from non-captive hosts sampled from natural habitats and find patterns with bioclimate and geophysical factors, as well as land use, host phylogeny, and trophic level/diet. Specifically, external microbiomes are best explained by variations in mean daily temperature range and precipitation seasonality. In contrast, internal microbiomes are best explained by host factors such as phylogeny/immune complexity and trophic level/diet, plus climate.<br><br>CONCLUSIONS: Internal microbiomes are predominantly associated with top-down effects, while climatic factors are stronger determinants of microbiomes on host external surfaces. Host immunity may act on microbiome diversity through top-down regulation analogous to predators in non-microbial ecosystems. Noting gaps in geographic and host sampling, this combined dataset represents a global baseline available for interrogation by future microbial ecology studies.}, }
@article {pmid31987701, year = {2020}, author = {Yadav, A and Vilcáez, J and Farag, IF and Johnson, B and Mueller, K and Youssef, NH and Elshahed, MS}, title = {Candidatus Mcinerneyibacterium aminivorans gen. nov., sp. nov., the first representative of the candidate phylum Mcinerneyibacteriota phyl. nov. recovered from a high temperature, high salinity tertiary oil reservoir in north central Oklahoma, USA.}, journal = {Systematic and applied microbiology}, volume = {43}, number = {2}, pages = {126057}, doi = {10.1016/j.syapm.2020.126057}, pmid = {31987701}, issn = {1618-0984}, mesh = {Bacterial Proteins/genetics ; Culture Media ; DNA, Bacterial/genetics ; Ecosystem ; Genome, Bacterial/genetics ; Gram-Negative Anaerobic Straight, Curved, and Helical Rods/*classification/*genetics/isolation &amp; purification/metabolism ; Oil and Gas Fields/chemistry/*microbiology ; Oklahoma ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Salinity ; Sequence Analysis, DNA ; Soybean Proteins/metabolism ; Temperature ; }, abstract = {We report on the characterization of a novel genomic assembly (ARYD3) recovered from formation water (17.6% salinity) and crude oil enrichment amended by isolated soy proteins (0.2%), and incubated for 100 days under anaerobic conditions at 50°C. Phylogenetic and phylogenomic analysis demonstrated that the ARYD3 is unaffiliated with all currently described bacterial phyla and candidate phyla, as evident by the low AAI (34.7%), shared gene content (19.4%), and 78.9% 16S rRNA gene sequence similarity to Halothiobacillus neapolitanus, its closest cultured relative. Genomic characterization predicts a slow-growing, non-spore forming, and non-motile Gram-negative rod. Adaptation to high salinity is potentially mediated by the production of the compatible solutes cyclic 2,3-diphosphoglycerate (cDPG), α-glucosylglycerate, as well as the uptake of glycine betaine. Metabolically, the genome encodes primarily aminolytic capabilities for a wide range of amino acids and peptides. Interestingly, evidence of propionate degradation to succinate via methyl-malonyl CoA was identified, suggesting possible capability for syntrophic propionate degradation. Analysis of ARYD3 global distribution patterns identified its occurrence in a very small fraction of Earth Microbiome Project datasets examined (318/27,068), where it consistently represented an extremely rare fraction (maximum 0.28%, average 0.004%) of the overall community. We propose the Candidatus name Mcinerneyibacterium aminivorans gen. nov, sp. nov. for ARYD3[T], with the genome serving as the type material for the novel family Mcinerneyibacteriaceae fam. nov., order Mcinerneyibacteriales ord. nov., class Mcinerneyibacteria class nov., and phylum Mcinerneyibacteriota phyl. nov. The type material genome assembly is deposited in GenBank under accession number VSIX00000000.}, }
@article {pmid33814114, year = {2020}, author = {Hopson, LM and Singleton, SS and David, JA and Basuchoudhary, A and Prast-Nielsen, S and Klein, P and Sen, S and Mazumder, R}, title = {Bioinformatics and machine learning in gastrointestinal microbiome research and clinical application.}, journal = {Progress in molecular biology and translational science}, volume = {176}, number = {}, pages = {141-178}, doi = {10.1016/bs.pmbts.2020.08.011}, pmid = {33814114}, issn = {1878-0814}, mesh = {Computational Biology ; *Gastrointestinal Microbiome ; Humans ; Machine Learning ; Metagenomics ; }, abstract = {The scientific community currently defines the human microbiome as all the bacteria, viruses, fungi, archaea, and eukaryotes that occupy the human body. When considering the variable locations, composition, diversity, and abundance of our microbial symbionts, the sheer volume of microorganisms reaches hundreds of trillions. With the onset of next generation sequencing (NGS), also known as high-throughput sequencing (HTS) technologies, the barriers to studying the human microbiome lowered significantly, making in-depth microbiome research accessible. Certain locations on the human body, such as the gastrointestinal, oral, nasal, and skin microbiomes have been heavily studied through community-focused projects like the Human Microbiome Project (HMP). In particular, the gastrointestinal microbiome (GM) has received significant attention due to links to neurological, immunological, and metabolic diseases, as well as cancer. Though HTS technologies allow deeper exploration of the GM, data informing the functional characteristics of microbiota and resulting effects on human function or disease are still sparse. This void is compounded by microbiome variability observed among humans through factors like genetics, environment, diet, metabolic activity, and even exercise; making GM research inherently difficult to study. This chapter describes an interdisciplinary approach to GM research with the goal of mitigating the hindrances of translating findings into a clinical setting. By applying tools and knowledge from microbiology, metagenomics, bioinformatics, machine learning, predictive modeling, and clinical study data from children with treatment-resistant epilepsy, we describe a proof-of-concept approach to clinical translation and precision application of GM research.}, }
@article {pmid31886477, year = {2021}, author = {Tomassi, D and Forzani, L and Duarte, S and Pfeiffer, RM}, title = {Sufficient dimension reduction for compositional data.}, journal = {Biostatistics (Oxford, England)}, volume = {22}, number = {4}, pages = {687-705}, pmid = {31886477}, issn = {1468-4357}, mesh = {Humans ; Likelihood Functions ; *Microbiota ; }, abstract = {Recent efforts to characterize the human microbiome and its relation to chronic diseases have led to a surge in statistical development for compositional data. We develop likelihood-based sufficient dimension reduction methods (SDR) to find linear combinations that contain all the information in the compositional data on an outcome variable, i.e., are sufficient for modeling and prediction of the outcome. We consider several models for the inverse regression of the compositional vector or transformations of it, as a function of outcome. They include normal, multinomial, and Poisson graphical models that allow for complex dependencies among observed counts. These methods yield efficient estimators of the reduction and can be applied to continuous or categorical outcomes. We incorporate variable selection into the estimation via penalties and address important invariance issues arising from the compositional nature of the data. We illustrate and compare our methods and some established methods for analyzing microbiome data in simulations and using data from the Human Microbiome Project. Displaying the data in the coordinate system of the SDR linear combinations allows visual inspection and facilitates comparisons across studies.}, }
@article {pmid31857734, year = {2020}, author = {Martiny, JBH and Whiteson, KL and Bohannan, BJM and David, LA and Hynson, NA and McFall-Ngai, M and Rawls, JF and Schmidt, TM and Abdo, Z and Blaser, MJ and Bordenstein, S and Bréchot, C and Bull, CT and Dorrestein, P and Eisen, JA and Garcia-Pichel, F and Gilbert, J and Hofmockel, KS and Holtz, ML and Knight, R and Mark Welch, DB and McDonald, D and Methé, B and Mouncey, NJ and Mueller, NT and Pfister, CA and Proctor, L and Sachs, JL}, title = {The emergence of microbiome centres.}, journal = {Nature microbiology}, volume = {5}, number = {1}, pages = {2-3}, pmid = {31857734}, issn = {2058-5276}, support = {K01 HL141589/HL/NHLBI NIH HHS/United States ; R21 AI149354/AI/NIAID NIH HHS/United States ; N00014-19-1-2313//United States Department of Defense | United States Navy | Office of Naval Research (ONR)/International ; DEB-1925761//NSF | BIO | Division of Environmental Biology (DEB)/International ; }, mesh = {Animals ; Capital Financing ; Communication ; Humans ; Interdisciplinary Research/economics/*organization &amp; administration/*trends ; *Microbiota ; }, }
@article {pmid31832327, year = {2019}, author = {Ma, ZS and Li, W}, title = {How and Why Men and Women Differ in Their Microbiomes: Medical Ecology and Network Analyses of the Microgenderome.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {6}, number = {23}, pages = {1902054}, pmid = {31832327}, issn = {2198-3844}, abstract = {Microgenderome or sexual dimorphism in microbiome refers to the bidirectional interactions between microbiotas, sex hormones, and immune systems, and it is highly relevant to disease susceptibility. A critical step in exploring microgenderome is to dissect the sex differences in key community ecology properties, which has not been systematically analyzed. This study aims at filling the gap by reanalyzing the Human Microbiome Project datasets with two objectives: (i) dissecting the sex differences in community diversity and their intersubject scaling, species composition, core/periphery species, and high-salience skeletons (species interactions); (ii) offering mechanistic interpretations for (i). Conceptually, the Vellend-Hanson synthesis of community ecology that stipulates selection, drift, speciation, and dispersal as the four processes driving community dynamics is followed. Methodologically, seven approaches reflecting the state-of-the-art research in medical ecology of human microbiomes are harnessed to achieve the objectives. It is postulated that the revealed microgenderome characteristics (categorized as seven aspects of differences/similarities) exert far reaching influences on disease susceptibility, and are primarily due to the sex difference in selection effects (deterministic fitness differences in microbial species and/or species interactions with each other or with their hosts), which are, in turn, shaped/modulated by host physiology (immunity, hormones, gut-brain communications, etc.).}, }
@article {pmid31822687, year = {2019}, author = {Eguíluz, VM and Salazar, G and Fernández-Gracia, J and Pearman, JK and Gasol, JM and Acinas, SG and Sunagawa, S and Irigoien, X and Duarte, CM}, title = {Scaling of species distribution explains the vast potential marine prokaryote diversity.}, journal = {Scientific reports}, volume = {9}, number = {1}, pages = {18710}, pmid = {31822687}, issn = {2045-2322}, mesh = {Aquatic Organisms/*classification ; *Biodiversity ; Demography ; Ecosystem ; Indian Ocean ; Microbiota ; Models, Theoretical ; Population Density ; Prokaryotic Cells/*classification ; Seawater ; }, abstract = {Global ocean expeditions have provided minimum estimates of ocean's prokaryote diversity, supported by apparent asymptotes in the number of prokaryotes with sampling effort, of about 40,000 species, representing <1% of the species cataloged in the Earth Microbiome Project, despite being the largest habitat in the biosphere. Here we demonstrate that the abundance of prokaryote OTUs follows a scaling that can be represented by a power-law distribution, and as a consequence, we demonstrate, mathematically and through simulations, that the asymptote of rarefaction curves is an apparent one, which is only reached with sample sizes approaching the entire ecosystem. We experimentally confirm these findings using exhaustive repeated sampling of a prokaryote community in the Red Sea and the exploration of global assessments of prokaryote diversity in the ocean. Our findings indicate that, far from having achieved a thorough sampling of prokaryote species abundance in the ocean, global expeditions provide just a start for this quest as the richness in the global ocean is much larger than estimated.}, }
@article {pmid31683170, year = {2019}, author = {Orlandi, E and Iacovelli, NA and Tombolini, V and Rancati, T and Polimeni, A and De Cecco, L and Valdagni, R and De Felice, F}, title = {Potential role of microbiome in oncogenesis, outcome prediction and therapeutic targeting for head and neck cancer.}, journal = {Oral oncology}, volume = {99}, number = {}, pages = {104453}, doi = {10.1016/j.oraloncology.2019.104453}, pmid = {31683170}, issn = {1879-0593}, mesh = {Carcinogenesis/*genetics ; Head and Neck Neoplasms/*genetics/*therapy ; Humans ; Immunotherapy/*methods ; Microbiota/*genetics ; Prognosis ; Treatment Outcome ; }, abstract = {In the last decade, human microbiome research is rapidly growing involving several fields of clinical medicine and population health. Although the microbiome seems to be linked to all sorts of diseases, cancer has the biggest potential to be investigated. Following the publication of the National Institute of Health - Human Microbiome Project (NIH-HMP), the link between Head and Neck Cancer (HNC) and microbiome seems to be a fast-moving field in research area. However, robust evidence-based literature is still quite scarce. Nevertheless the relationship between oral microbiome and HNC could have important consequences for prevention and early detection of this type of tumors. The aims of the present review are: (i) to discuss current pre-clinical evidence of a role of oral microbiome in HNC; (ii) to report recent developments in understanding the human microbiome's relationship with HNC oncogenesis; (iii) to explore the issue of treatment response and treatment toxicity; (iv) to describe the role of microbiota as potentially modifiable factor suitable for targeting by therapeutics. Further studies are needed to better establish the causal relationship between oral microbiome and HNC oncogenesis. Future trials should continue to explore oral microbiome in order to build the scientific and clinical rationale of HNC preventative and ameliorate treatment outcome.}, }
@article {pmid31649646, year = {2019}, author = {Engevik, MA and Morra, CN and Röth, D and Engevik, K and Spinler, JK and Devaraj, S and Crawford, SE and Estes, MK and Kalkum, M and Versalovic, J}, title = {Microbial Metabolic Capacity for Intestinal Folate Production and Modulation of Host Folate Receptors.}, journal = {Frontiers in microbiology}, volume = {10}, number = {}, pages = {2305}, pmid = {31649646}, issn = {1664-302X}, support = {P30 CA033572/CA/NCI NIH HHS/United States ; P30 DK056338/DK/NIDDK NIH HHS/United States ; U01 CA170930/CA/NCI NIH HHS/United States ; }, abstract = {Microbial metabolites, including B complex vitamins contribute to diverse aspects of human health. Folate, or vitamin B9, refers to a broad category of biomolecules that include pterin, para-aminobenzoic acid (pABA), and glutamate subunits. Folates are required for DNA synthesis and epigenetic regulation. In addition to dietary nutrients, the gut microbiota has been recognized as a source of B complex vitamins, including folate. This study evaluated the predicted folate synthesis capabilities in the genomes of human commensal microbes identified in the Human Microbiome Project and folate production by representative strains of six human intestinal bacterial phyla. Bacterial folate synthesis genes were ubiquitous across 512 gastrointestinal reference genomes with 13% of the genomes containing all genes required for complete de novo folate synthesis. An additional 39% of the genomes had the genetic capacity to synthesize folates in the presence of pABA, an upstream intermediate that can be obtained through diet or from other intestinal microbes. Bacterial folate synthesis was assessed during exponential and stationary phase growth through the evaluation of expression of select folate synthesis genes, quantification of total folate production, and analysis of folate polyglutamylation. Increased expression of key folate synthesis genes was apparent in exponential phase, and increased folate polyglutamylation occurred during late stationary phase. Of the folate producers, we focused on the commensal Lactobacillus reuteri to examine host-microbe interactions in relation to folate and examined folate receptors in the physiologically relevant human enteroid model. RNAseq data revealed segment-specific folate receptor distribution. Treatment of human colonoid monolayers with conditioned media (CM) from wild-type L. reuteri did not influence the expression of key folate transporters proton-coupled folate transporter (PCFT) or reduced folate carrier (RFC). However, CM from L. reuteri containing a site-specific inactivation of the folC gene, which prevents the bacteria from synthesizing a polyglutamate tail on folate, significantly upregulated RFC expression. No effects were observed using L. reuteri with a site inactivation of folC2, which results in no folate production. This work sheds light on the contributions of microbial folate to overall folate status and mammalian host metabolism.}, }
@article {pmid31617360, year = {2019}, author = {Lam, KL and Cheung, PC}, title = {Carbohydrate-Based Prebiotics in Targeted Modulation of Gut Microbiome.}, journal = {Journal of agricultural and food chemistry}, volume = {67}, number = {45}, pages = {12335-12340}, doi = {10.1021/acs.jafc.9b04811}, pmid = {31617360}, issn = {1520-5118}, mesh = {Animals ; Bacteria/classification/genetics/isolation &amp; purification/metabolism ; Carbohydrates/chemistry/*pharmacology ; Gastrointestinal Microbiome/*drug effects ; Humans ; Intestines/microbiology ; Prebiotics/*analysis ; }, abstract = {The Human Microbiome Project has prompted unprecedented advancement in microbiome science. Personalized microbiome modulation with precision (PMMP) is one of the emerging yet challenging fields in microbiome research. Carbohydrate-based prebiotics (CBPs) have been shown to modulate the gut microbiome to various extents according to different structural characteristics, such as degree of polymerization, branching, glycosidic linkage, monosaccharide profile, and chemical modification. Subsequently, a targeted modulation of the microbiome might be achieved by using CBPs with a specific structure. A multidimensional database can be established based on the structure-microbiome and structure-microbial-marker relationships. Such relationships could facilitate the development of synbiotics and PMMP.}, }
@article {pmid31600339, year = {2019}, author = {Dheilly, NM and Martínez Martínez, J and Rosario, K and Brindley, PJ and Fichorova, RN and Kaye, JZ and Kohl, KD and Knoll, LJ and Lukeš, J and Perkins, SL and Poulin, R and Schriml, L and Thompson, LR}, title = {Parasite microbiome project: Grand challenges.}, journal = {PLoS pathogens}, volume = {15}, number = {10}, pages = {e1008028}, pmid = {31600339}, issn = {1553-7374}, support = {U01 AI065871/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Bacteria/*classification ; *Evolution, Molecular ; *Host-Pathogen Interactions ; Humans ; *Microbiota ; Parasites/*microbiology ; }, }
@article {pmid31588499, year = {2020}, author = {Bradley, PH and Pollard, KS}, title = {phylogenize: correcting for phylogeny reveals genes associated with microbial distributions.}, journal = {Bioinformatics (Oxford, England)}, volume = {36}, number = {4}, pages = {1289-1290}, pmid = {31588499}, issn = {1367-4811}, mesh = {Humans ; *Microbiota ; Phylogeny ; RNA, Ribosomal, 16S ; }, abstract = {SUMMARY: Phylogenetic comparative methods are powerful but presently under-utilized ways to identify microbial genes underlying differences in community composition. These methods help to identify functionally important genes because they test for associations beyond those expected when related microbes occupy similar environments. We present phylogenize, a pipeline with web, QIIME 2 and R interfaces that allows researchers to perform phylogenetic regression on 16S amplicon and shotgun sequencing data and to visualize results. phylogenize applies broadly to both host-associated and environmental microbiomes. Using Human Microbiome Project and Earth Microbiome Project data, we show that phylogenize draws similar conclusions from 16S versus shotgun sequencing and reveals both known and candidate pathways associated with host colonization.<br><br>phylogenize is available at https://phylogenize.org and https://bitbucket.org/pbradz/phylogenize.<br><br>SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.}, }
@article {pmid31506265, year = {2019}, author = {Zhang, CJ and Pan, J and Duan, CH and Wang, YM and Liu, Y and Sun, J and Zhou, HC and Song, X and Li, M}, title = {Prokaryotic Diversity in Mangrove Sediments across Southeastern China Fundamentally Differs from That in Other Biomes.}, journal = {mSystems}, volume = {4}, number = {5}, pages = {}, pmid = {31506265}, issn = {2379-5077}, abstract = {Mangroves, as a blue carbon reservoir, provide an environment for a variety of microorganisms. Mangroves lie in special locations connecting coastal and estuarine areas and experience fluctuating conditions, which are expected to intensify with climate change, creating a need to better understand the relative roles of stochastic and deterministic processes in shaping microbial community assembly. Here, a study of microbial communities inhabiting mangrove sediments across southeastern China, spanning mangroves in six nature reserves, was conducted. We performed high-throughput DNA sequencing of these samples and compared them with data of 1,370 sediment samples collected from the Earth Microbiome Project (EMP) to compare the microbial diversity of mangroves with that of other biomes. Our results showed that prokaryotic alpha diversity in mangroves was significantly higher than that in other biomes and that microbial beta diversity generally clustered according to biome types. The core operational taxonomic units (OTUs) in mangroves were mostly assigned to Gammaproteobacteria, Deltaproteobacteria, Chloroflexi, and Euryarchaeota The majority of beta nearest-taxon index values were higher than 2, indicating that community assembly in mangroves was better explained through a deterministic process than through a stochastic process. Mean annual precipitation (MAP) and total organic carbon (TOC) were main deterministic factors explaining variation in the microbial community. This study fills a gap in addressing the unique microbial diversity of mangrove ecosystems and their microbial community assembly mechanisms.IMPORTANCE Understanding the underlying mechanisms of microbial community assembly patterns is a vital issue in microbial ecology. Mangroves, as an important and special ecosystem, provide a unique environment for examining the relative importance of stochastic and deterministic processes. We made the first global-scale comparison and found that microbial diversity was significantly different in mangrove sediments compared to that of other biomes. Furthermore, our results suggest that a deterministic process is more important in shaping microbial community assembly in mangroves.}, }
@article {pmid31502171, year = {2020}, author = {Kumar, M and Singh, P and Murugesan, S and Vetizou, M and McCulloch, J and Badger, JH and Trinchieri, G and Al Khodor, S}, title = {Microbiome as an Immunological Modifier.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {2055}, number = {}, pages = {595-638}, pmid = {31502171}, issn = {1940-6029}, support = {ZIA BC011153/ImNIH/Intramural NIH HHS/United States ; }, mesh = {Age Factors ; Aged ; Bacteria/*classification/genetics/isolation &amp; purification ; Bacterial Proteins/*genetics ; Gene Expression Profiling ; Gene Expression Regulation, Bacterial ; High-Throughput Nucleotide Sequencing ; Humans ; Metagenomics/*methods ; Microbiota ; Middle Aged ; Sequence Analysis, DNA ; }, abstract = {Humans are living ecosystems composed of human cells and microbes. The microbiome is the collection of microbes (microbiota) and their genes. Recent breakthroughs in the high-throughput sequencing technologies have made it possible for us to understand the composition of the human microbiome. Launched by the National Institutes of Health in USA, the human microbiome project indicated that our bodies harbor a wide array of microbes, specific to each body site with interpersonal and intrapersonal variabilities. Numerous studies have indicated that several factors influence the development of the microbiome including genetics, diet, use of antibiotics, and lifestyle, among others. The microbiome and its mediators are in a continuous cross talk with the host immune system; hence, any imbalance on one side is reflected on the other. Dysbiosis (microbiota imbalance) was shown in many diseases and pathological conditions such as inflammatory bowel disease, celiac disease, multiple sclerosis, rheumatoid arthritis, asthma, diabetes, and cancer. The microbial composition mirrors inflammation variations in certain disease conditions, within various stages of the same disease; hence, it has the potential to be used as a biomarker.}, }
@article {pmid31455640, year = {2019}, author = {Creekmore, BC and Gray, JH and Walton, WG and Biernat, KA and Little, MS and Xu, Y and Liu, J and Gharaibeh, RZ and Redinbo, MR}, title = {Mouse Gut Microbiome-Encoded β-Glucuronidases Identified Using Metagenome Analysis Guided by Protein Structure.}, journal = {mSystems}, volume = {4}, number = {4}, pages = {}, pmid = {31455640}, issn = {2379-5077}, support = {R01 CA098468/CA/NCI NIH HHS/United States ; R01 CA207416/CA/NCI NIH HHS/United States ; }, abstract = {Gut microbial β-glucuronidase (GUS) enzymes play important roles in drug efficacy and toxicity, intestinal carcinogenesis, and mammalian-microbial symbiosis. Recently, the first catalog of human gut GUS proteins was provided for the Human Microbiome Project stool sample database and revealed 279 unique GUS enzymes organized into six categories based on active-site structural features. Because mice represent a model biomedical research organism, here we provide an analogous catalog of mouse intestinal microbial GUS proteins-a mouse gut GUSome. Using metagenome analysis guided by protein structure, we examined 2.5 million unique proteins from a comprehensive mouse gut metagenome created from several mouse strains, providers, housing conditions, and diets. We identified 444 unique GUS proteins and organized them into six categories based on active-site features, similarly to the human GUSome analysis. GUS enzymes were encoded by the major gut microbial phyla, including Firmicutes (60%) and Bacteroidetes (21%), and there were nearly 20% for which taxonomy could not be assigned. No differences in gut microbial gus gene composition were observed for mice based on sex. However, mice exhibited gus differences based on active-site features associated with provider, location, strain, and diet. Furthermore, diet yielded the largest differences in gus composition. Biochemical analysis of two low-fat-associated GUS enzymes revealed that they are variable with respect to their efficacy of processing both sulfated and nonsulfated heparan nonasaccharides containing terminal glucuronides.IMPORTANCE Mice are commonly employed as model organisms of mammalian disease; as such, our understanding of the compositions of their gut microbiomes is critical to appreciating how the mouse and human gastrointestinal tracts mirror one another. GUS enzymes, with importance in normal physiology and disease, are an attractive set of proteins to use for such analyses. Here we show that while the specific GUS enzymes differ at the sequence level, a core GUSome functionality appears conserved between mouse and human gastrointestinal bacteria. Mouse strain, provider, housing location, and diet exhibit distinct GUSomes and gus gene compositions, but sex seems not to affect the GUSome. These data provide a basis for understanding the gut microbial GUS enzymes present in commonly used laboratory mice. Further, they demonstrate the utility of metagenome analysis guided by protein structure to provide specific sets of functionally related proteins from whole-genome metagenome sequencing data.}, }
@article {pmid31425594, year = {2019}, author = {Mougeot, JC and Stevens, CB and Morton, DS and Brennan, MT and Mougeot, FB}, title = {Oral Microbiome and Cancer Therapy-Induced Oral Mucositis.}, journal = {Journal of the National Cancer Institute. Monographs}, volume = {2019}, number = {53}, pages = {}, doi = {10.1093/jncimonographs/lgz002}, pmid = {31425594}, issn = {1745-6614}, mesh = {Disease Susceptibility ; Humans ; Intestinal Mucosa/metabolism/microbiology/pathology ; Metagenome ; Metagenomics/methods ; *Microbiota ; Mouth Mucosa/microbiology/pathology ; Neoplasms/*complications/therapy ; Stomatitis/diagnosis/drug therapy/*etiology/prevention &amp; control ; Systems Biology/methods ; }, abstract = {Characterization of the role of oral microbiome in cancer therapy-induced oral mucositis (CTOM) is critical in preventing the clinically deleterious effects on patients' health that are associated with CTOM. Funding initiatives related to the National Institutes of Health human microbiome project have resulted in groundbreaking advancements in biology and medicine during the last decade. These advancements have shown that a human being is in fact a superorganism made of human cells and associated symbiotic or commensal microbiota. In this review, we describe the state of science as it relates to fundamental knowledge on oral microbiome and its role in CTOM. We also discuss how state-of-the-art technologies and systems biology tools may be used to help tackle the difficult challenges ahead to develop effective treatments or preventive therapies for oral mucositis. We make a clear distinction between disease processes pertaining to the oral microbiome, which includes opportunistic pathogens that may be defined as pathobionts, and those infectious disease processes initiated by exogenous pathogens. We also explored the extent to which knowledge from the gastrointestinal tract in disease and intestinal mucositis could help us better understand CTOM pathobiology. Finally, we propose a model in which the oral microbiome participates in the current five-step CTOM pathobiology model. With the advent of more sophisticated metagenomics technologies and methods of analysis, much hope lies ahead to implement an effective holistic approach to treat cancer patients affected by CTOM.}, }
@article {pmid31409660, year = {2019}, author = {Zhang, S and Song, W and Wemheuer, B and Reveillaud, J and Webster, N and Thomas, T}, title = {Comparative Genomics Reveals Ecological and Evolutionary Insights into Sponge-Associated Thaumarchaeota.}, journal = {mSystems}, volume = {4}, number = {4}, pages = {}, pmid = {31409660}, issn = {2379-5077}, abstract = {Thaumarchaeota are frequently reported to associate with marine sponges (phylum Porifera); however, little is known about the features that distinguish them from their free-living thaumarchaeal counterparts. In this study, thaumarchaeal metagenome-assembled genomes (MAGs) were reconstructed from metagenomic data sets derived from the marine sponges Hexadella detritifera, Hexadella cf. detritifera, and Stylissa flabelliformis Phylogenetic and taxonomic analyses revealed that the three thaumarchaeal MAGs represent two new species within the genus Nitrosopumilus and one novel genus, for which we propose the names "Candidatus [U]Nitrosopumilus hexadellus," "Candidatus [U]Nitrosopumilus detritiferus," and "Candidatus [U]Cenporiarchaeum stylissum" (the U superscript indicates that the taxon is uncultured). Comparison of these genomes to data from the Sponge Earth Microbiome Project revealed that "Ca [U]Cenporiarchaeum stylissum" has been exclusively detected in sponges and can hence be classified as a specialist, while "Ca [U]Nitrosopumilus detritiferus" and "Ca [U]Nitrosopumilus hexadellus" are also detected outside the sponge holobiont and likely lead a generalist lifestyle. Comparison of the sponge-associated MAGs to genomes of free-living Thaumarchaeota revealed signatures that indicate functional features of a sponge-associated lifestyle, and these features were related to nutrient transport and metabolism, restriction-modification, defense mechanisms, and host interactions. Each species exhibited distinct functional traits, suggesting that they have reached different stages of evolutionary adaptation and/or occupy distinct ecological niches within their sponge hosts. Our study therefore offers new evolutionary and ecological insights into the symbiosis between sponges and their thaumarchaeal symbionts.IMPORTANCE Sponges represent ecologically important models to understand the evolution of symbiotic interactions of metazoans with microbial symbionts. Thaumarchaeota are commonly found in sponges, but their potential adaptations to a host-associated lifestyle are largely unknown. Here, we present three novel sponge-associated thaumarchaeal species and compare their genomic and predicted functional features with those of closely related free-living counterparts. We found different degrees of specialization of these thaumarchaeal species to the sponge environment that is reflected in their host distribution and their predicted molecular and metabolic properties. Our results indicate that Thaumarchaeota may have reached different stages of evolutionary adaptation in their symbiosis with sponges.}, }
@article {pmid31399723, year = {2019}, author = {Bolyen, E and Rideout, JR and Dillon, MR and Bokulich, NA and Abnet, CC and Al-Ghalith, GA and Alexander, H and Alm, EJ and Arumugam, M and Asnicar, F and Bai, Y and Bisanz, JE and Bittinger, K and Brejnrod, A and Brislawn, CJ and Brown, CT and Callahan, BJ and Caraballo-Rodríguez, AM and Chase, J and Cope, EK and Da Silva, R and Diener, C and Dorrestein, PC and Douglas, GM and Durall, DM and Duvallet, C and Edwardson, CF and Ernst, M and Estaki, M and Fouquier, J and Gauglitz, JM and Gibbons, SM and Gibson, DL and Gonzalez, A and Gorlick, K and Guo, J and Hillmann, B and Holmes, S and Holste, H and Huttenhower, C and Huttley, GA and Janssen, S and Jarmusch, AK and Jiang, L and Kaehler, BD and Kang, KB and Keefe, CR and Keim, P and Kelley, ST and Knights, D and Koester, I and Kosciolek, T and Kreps, J and Langille, MGI and Lee, J and Ley, R and Liu, YX and Loftfield, E and Lozupone, C and Maher, M and Marotz, C and Martin, BD and McDonald, D and McIver, LJ and Melnik, AV and Metcalf, JL and Morgan, SC and Morton, JT and Naimey, AT and Navas-Molina, JA and Nothias, LF and Orchanian, SB and Pearson, T and Peoples, SL and Petras, D and Preuss, ML and Pruesse, E and Rasmussen, LB and Rivers, A and Robeson, MS and Rosenthal, P and Segata, N and Shaffer, M and Shiffer, A and Sinha, R and Song, SJ and Spear, JR and Swafford, AD and Thompson, LR and Torres, PJ and Trinh, P and Tripathi, A and Turnbaugh, PJ and Ul-Hasan, S and van der Hooft, JJJ and Vargas, F and Vázquez-Baeza, Y and Vogtmann, E and von Hippel, M and Walters, W and Wan, Y and Wang, M and Warren, J and Weber, KC and Williamson, CHD and Willis, AD and Xu, ZZ and Zaneveld, JR and Zhang, Y and Zhu, Q and Knight, R and Caporaso, JG}, title = {Author Correction: Reproducible, interactive, scalable and extensible microbiome data science using QIIME 2.}, journal = {Nature biotechnology}, volume = {37}, number = {9}, pages = {1091}, doi = {10.1038/s41587-019-0252-6}, pmid = {31399723}, issn = {1546-1696}, abstract = {An amendment to this paper has been published and can be accessed via a link at the top of the paper.}, }
@article {pmid31384012, year = {2019}, author = {Klinges, JG and Rosales, SM and McMinds, R and Shaver, EC and Shantz, AA and Peters, EC and Eitel, M and Wörheide, G and Sharp, KH and Burkepile, DE and Silliman, BR and Vega Thurber, RL}, title = {Phylogenetic, genomic, and biogeographic characterization of a novel and ubiquitous marine invertebrate-associated Rickettsiales parasite, Candidatus Aquarickettsia rohweri, gen. nov., sp. nov.}, journal = {The ISME journal}, volume = {13}, number = {12}, pages = {2938-2953}, pmid = {31384012}, issn = {1751-7370}, mesh = {Animals ; Aquatic Organisms/*microbiology ; Genome, Bacterial ; Genomics ; Gram-Negative Bacterial Infections/microbiology/*veterinary ; Invertebrates/*microbiology ; Parasites/classification/genetics/isolation &amp; purification ; *Phylogeny ; Rickettsiales/classification/genetics/*isolation &amp; purification ; }, abstract = {Bacterial symbionts are integral to the health and homeostasis of invertebrate hosts. Notably, members of the Rickettsiales genus Wolbachia influence several aspects of the fitness and evolution of their terrestrial hosts, but few analogous partnerships have been found in marine systems. We report here the genome, phylogenetics, and biogeography of a ubiquitous and novel Rickettsiales species that primarily associates with marine organisms. We previously showed that this bacterium was found in scleractinian corals, responds to nutrient exposure, and is associated with reduced host growth and increased mortality. This bacterium, like other Rickettsiales, has a reduced genome indicative of a parasitic lifestyle. Phylogenetic analysis places this Rickettsiales within a new genus we define as "Candidatus Aquarickettsia." Using data from the Earth Microbiome Project and SRA databases, we also demonstrate that members of "Ca. Aquarickettsia" are found globally in dozens of invertebrate lineages. The coral-associated "Candidatus A. rohweri" is the first finished genome in this new clade. "Ca. A. rohweri" lacks genes to synthesize most sugars and amino acids but possesses several genes linked to pathogenicity including Tlc, an antiporter that exchanges host ATP for ADP, and a complete Type IV secretion system. Despite its inability to metabolize nitrogen, "Ca. A. rohweri" possesses the NtrY-NtrX two-component system involved in sensing and responding to extracellular nitrogen. Given these data, along with visualization of the parasite in host tissues, we hypothesize that "Ca. A. rohweri" reduces coral health by consuming host nutrients and energy, thus weakening and eventually killing host cells. Last, we hypothesize that nutrient enrichment, which is increasingly common on coral reefs, encourages unrestricted growth of "Ca. A. rohweri" in its host by providing abundant N-rich metabolites to be scavenged.}, }
@article {pmid31341288, year = {2019}, author = {Bolyen, E and Rideout, JR and Dillon, MR and Bokulich, NA and Abnet, CC and Al-Ghalith, GA and Alexander, H and Alm, EJ and Arumugam, M and Asnicar, F and Bai, Y and Bisanz, JE and Bittinger, K and Brejnrod, A and Brislawn, CJ and Brown, CT and Callahan, BJ and Caraballo-Rodríguez, AM and Chase, J and Cope, EK and Da Silva, R and Diener, C and Dorrestein, PC and Douglas, GM and Durall, DM and Duvallet, C and Edwardson, CF and Ernst, M and Estaki, M and Fouquier, J and Gauglitz, JM and Gibbons, SM and Gibson, DL and Gonzalez, A and Gorlick, K and Guo, J and Hillmann, B and Holmes, S and Holste, H and Huttenhower, C and Huttley, GA and Janssen, S and Jarmusch, AK and Jiang, L and Kaehler, BD and Kang, KB and Keefe, CR and Keim, P and Kelley, ST and Knights, D and Koester, I and Kosciolek, T and Kreps, J and Langille, MGI and Lee, J and Ley, R and Liu, YX and Loftfield, E and Lozupone, C and Maher, M and Marotz, C and Martin, BD and McDonald, D and McIver, LJ and Melnik, AV and Metcalf, JL and Morgan, SC and Morton, JT and Naimey, AT and Navas-Molina, JA and Nothias, LF and Orchanian, SB and Pearson, T and Peoples, SL and Petras, D and Preuss, ML and Pruesse, E and Rasmussen, LB and Rivers, A and Robeson, MS and Rosenthal, P and Segata, N and Shaffer, M and Shiffer, A and Sinha, R and Song, SJ and Spear, JR and Swafford, AD and Thompson, LR and Torres, PJ and Trinh, P and Tripathi, A and Turnbaugh, PJ and Ul-Hasan, S and van der Hooft, JJJ and Vargas, F and Vázquez-Baeza, Y and Vogtmann, E and von Hippel, M and Walters, W and Wan, Y and Wang, M and Warren, J and Weber, KC and Williamson, CHD and Willis, AD and Xu, ZZ and Zaneveld, JR and Zhang, Y and Zhu, Q and Knight, R and Caporaso, JG}, title = {Reproducible, interactive, scalable and extensible microbiome data science using QIIME 2.}, journal = {Nature biotechnology}, volume = {37}, number = {8}, pages = {852-857}, pmid = {31341288}, issn = {1546-1696}, support = {R35 GM133420/GM/NIGMS NIH HHS/United States ; U54 MD012388/MD/NIMHD NIH HHS/United States ; U54 CA143925/CA/NCI NIH HHS/United States ; T32 ES015459/ES/NIEHS NIH HHS/United States ; Z99 CA999999/ImNIH/Intramural NIH HHS/United States ; }, mesh = {*Computational Biology ; *Data Science ; Databases, Factual ; Humans ; *Microbiota ; *Software ; }, }
@article {pmid31312608, year = {2019}, author = {Gallon, P and Parekh, M and Ferrari, S and Fasolo, A and Ponzin, D and Borroni, D}, title = {Metagenomics in ophthalmology: Hypothesis or real prospective?.}, journal = {Biotechnology reports (Amsterdam, Netherlands)}, volume = {23}, number = {}, pages = {e00355}, pmid = {31312608}, issn = {2215-017X}, abstract = {Metagenomic analysis was originally associated with the studies of genetic material from environmental samples. But, with the advent of the Human Microbiome Project, it has now been applied in clinical practices. The ocular surface (OS) is the most exposed part of the eye, colonized by several microbial communities (both, OS and environmental) that contribute to the maintenance of the physiological state. Limited knowledge has been acquired on these microbes due to the limitations of conventional diagnostic methods. Emerging fields of research are focusing on Next Generation Sequencing (NGS) technologies to obtain reliable information on the OS microbiome. Currently only pre-specified pathogens can be detected by conventional culture-based techniques or Polymerase Chain Reaction (PCR), but there are conditions to state whether metagenomics could revolutionize the diagnosis of ocular diseases. The aim of this review is to provide an updated overview of the studies involving NGS technology for OS microbiome.}, }
@article {pmid31311141, year = {2019}, author = {Paoli, A and Mancin, L and Bianco, A and Thomas, E and Mota, JF and Piccini, F}, title = {Ketogenic Diet and Microbiota: Friends or Enemies?.}, journal = {Genes}, volume = {10}, number = {7}, pages = {}, pmid = {31311141}, issn = {2073-4425}, mesh = {Animals ; Biological Variation, Individual ; Carbohydrate Metabolism ; *Diet, Ketogenic ; Gastrointestinal Microbiome ; Humans ; Ketosis ; *Microbiota ; }, abstract = {Over the last years, a growing body of evidence suggests that gut microbial communities play a fundamental role in many aspects of human health and diseases. The gut microbiota is a very dynamic entity influenced by environment and nutritional behaviors. Considering the influence of such a microbial community on human health and its multiple mechanisms of action as the production of bioactive compounds, pathogens protection, energy homeostasis, nutrients metabolism and regulation of immunity, establishing the influences of different nutritional approach is of pivotal importance. The very low carbohydrate ketogenic diet is a very popular dietary approach used for different aims: from weight loss to neurological diseases. The aim of this review is to dissect the complex interactions between ketogenic diet and gut microbiota and how this large network may influence human health.}, }
@article {pmid31301004, year = {2019}, author = {Li, JKM and Chiu, PKF and Ng, CF}, title = {The impact of microbiome in urological diseases: a systematic review.}, journal = {International urology and nephrology}, volume = {51}, number = {10}, pages = {1677-1697}, pmid = {31301004}, issn = {1573-2584}, mesh = {Humans ; *Microbiota ; Urologic Diseases/*microbiology ; }, abstract = {OBJECTIVE: The term microbiome is used to signify the ecological community of commensal, symbiotic, and pathogenic microorganisms that share our body space, in which there were increasing evidences to suggest that they might have potential roles in various medical conditions. While the study of microbiome in the urinary system is not as robust as the systems included in the Human Microbiome Project, there are still evidences in the literature showing that microbiome may have a role in urological diseases. Therefore, we would like to perform a systematic review on the topic and summarize the available evidence on the impact of microbiome on urological diseases.<br><br>METHODOLOGY: This review was performed according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement. After screening 589 abstracts and including additional studies (such as references from review papers), 76 studies were included for review and discussion.<br><br>RESULTS: Studies had suggested that there were correlations of microbiome of different body cavities (e.g., fecal, urinary and seminal fluid) with urological diseases. Also, different diseases would have different microbiome profile in different body cavities. Unfortunately, the studies on the association of microbiome and urological diseases were still either weak or inconsistent.<br><br>CONCLUSION: Studies suggested that there might be some relationship between microbiome and various urological diseases. However, further large-scale studies with control of confounding factors should be performed under a standardized methodology in order to have better understanding of the relationship. Also, more standardized reporting protocol for microbiome studies should be considered for better communications in future studies.}, }
@article {pmid31279340, year = {2019}, author = {Velsko, IM and Fellows Yates, JA and Aron, F and Hagan, RW and Frantz, LAF and Loe, L and Martinez, JBR and Chaves, E and Gosden, C and Larson, G and Warinner, C}, title = {Microbial differences between dental plaque and historic dental calculus are related to oral biofilm maturation stage.}, journal = {Microbiome}, volume = {7}, number = {1}, pages = {102}, pmid = {31279340}, issn = {2049-2618}, mesh = {Bacteria/*classification ; *Bacterial Physiological Phenomena ; Bacterial Proteins/genetics ; Biofilms/*growth &amp; development ; Bone and Bones/microbiology ; DNA, Ancient/analysis ; DNA, Bacterial/genetics ; Dental Calculus/history/*microbiology ; Dental Plaque/*microbiology ; Female ; History, Ancient ; Humans ; Male ; Metagenomics ; Microbiota/*physiology ; Periodontal Diseases/microbiology ; Proteomics ; Tooth/*microbiology ; }, abstract = {BACKGROUND: Dental calculus, calcified oral plaque biofilm, contains microbial and host biomolecules that can be used to study historic microbiome communities and host responses. Dental calculus does not typically accumulate as much today as historically, and clinical oral microbiome research studies focus primarily on living dental plaque biofilm. However, plaque and calculus reflect different conditions of the oral biofilm, and the differences in microbial characteristics between the sample types have not yet been systematically explored. Here, we compare the microbial profiles of modern dental plaque, modern dental calculus, and historic dental calculus to establish expected differences between these substrates.<br><br>RESULTS: Metagenomic data was generated from modern and historic calculus samples, and dental plaque metagenomic data was downloaded from the Human Microbiome Project. Microbial composition and functional profile were assessed. Metaproteomic data was obtained from a subset of historic calculus samples. Comparisons between microbial, protein, and metabolomic profiles revealed distinct taxonomic and metabolic functional profiles between plaque, modern calculus, and historic calculus, but not between calculus collected from healthy teeth and periodontal disease-affected teeth. Species co-exclusion was related to biofilm environment. Proteomic profiling revealed that healthy tooth samples contain low levels of bacterial virulence proteins and a robust innate immune response. Correlations between proteomic and metabolomic profiles suggest co-preservation of bacterial lipid membranes and membrane-associated proteins.<br><br>CONCLUSIONS: Overall, we find that there are systematic microbial differences between plaque and calculus related to biofilm physiology, and recognizing these differences is important for accurate data interpretation in studies comparing dental plaque and calculus.}, }
@article {pmid31202028, year = {2019}, author = {Liu, T and Chen, X and Xu, Y and Wu, W and Tang, W and Chen, Z and Ji, G and Peng, J and Jiang, Q and Xiao, J and Li, X and Zeng, W and Xu, X and Hu, J and Guo, Y and Zou, F and Du, Q and Zhou, H and He, Y and Ma, W}, title = {Gut microbiota partially mediates the effects of fine particulate matter on type 2 diabetes: Evidence from a population-based epidemiological study.}, journal = {Environment international}, volume = {130}, number = {}, pages = {104882}, doi = {10.1016/j.envint.2019.05.076}, pmid = {31202028}, issn = {1873-6750}, mesh = {Adult ; Aged ; Air Pollutants/*adverse effects ; Blood Glucose/analysis ; Diabetes Mellitus, Type 2/blood/*epidemiology/microbiology ; Environmental Exposure/adverse effects ; Feces/microbiology ; Female ; *Gastrointestinal Microbiome ; Humans ; Male ; Middle Aged ; Particulate Matter/*adverse effects ; }, abstract = {BACKGROUND: Experimental studies have indicated that alterations in the gut microbiota might play a role in the pathway of diabetes induction resulting from particulate matter pollution with aerodynamic diameters < 2.5 μm (PM2.5). However, few human studies have examined such experimental findings. Here, we examine the mediating effects of gut microbial dysbiosis on the associations between PM2.5 and particulate matter pollution with aerodynamic diameters < 1 μm (PM1) on diabetes using the Guangdong Gut Microbiome Project (GGMP) dataset.<br><br>METHODS: A multistage cluster sampling method was employed to recruit adult participants from communities in Guangdong. Each participant was interviewed using a questionnaire, fasting blood and stool samples were collected, and the exposure to air pollutants was assessed using a spatiotemporal land-use regression model. The mediation analysis was conducted to estimate the associations among air pollutants, gut microbiota diversity and diabetes.<br><br>RESULTS: Both PM2.5 and PM1 were positively associated with the risks of impaired fasting glucose (IFG) or type 2 diabetes and negatively associated with alpha diversity indices of the gut microbiota. The mediation analyses indicated that the associations of PM2.5 and PM1 with the risk of type 2 diabetes were partially mediated by the decrease in gut microbiota diversity. Moreover, we found that 79 (PM2.5 on IFG), 84 (PM2.5 on type 2 diabetes), 83 (PM1 on IFG) and 89 (PM1 on type 2 diabetes) bacterial taxa could partially mediate the associations of PM2.5 and PM1 with IFG and type 2 diabetes, respectively. The relative abundance of most Firmicutes, Proteobacteria and Verrucomicrobia bacteria were negatively associated with particulate matter (PM) concentrations and the risks of diabetes.<br><br>CONCLUSIONS: Long-term exposure to PM may increase the risk of diabetes, and alterations in the gut microbiota partially explained these associations.}, }
@article {pmid31185820, year = {2019}, author = {Greene, LK and Clayton, JB and Rothman, RS and Semel, BP and Semel, MA and Gillespie, TR and Wright, PC and Drea, CM}, title = {Local habitat, not phylogenetic relatedness, predicts gut microbiota better within folivorous than frugivorous lemur lineages.}, journal = {Biology letters}, volume = {15}, number = {6}, pages = {20190028}, pmid = {31185820}, issn = {1744-957X}, mesh = {Animals ; *Gastrointestinal Microbiome ; *Lemur ; *Lemuridae ; Madagascar ; Phylogeny ; RNA, Ribosomal, 16S ; }, abstract = {Both host phylogenetic placement and feeding strategy influence the structure of the gut microbiome (GMB); however, parsing their relative contributions presents a challenge. To meet this challenge, we compared GMB structure in two genera of lemurs characterized by different dietary specializations, the frugivorous brown lemurs (Eulemur spp.) and the folivorous sifakas (Propithecus spp.). These genera sympatrically occupy similar habitats (dry forests and rainforests) and diverged over similar evolutionary timescales. We collected fresh faeces from 12 species (six per host genus), at seven sites across Madagascar, and sequenced the 16S rRNA gene to determine GMB membership, diversity and variability. The lemurs' GMBs clustered predominantly by host genus; nevertheless, within genera, host relatedness did not predict GMB distance between species. The GMBs of brown lemurs had greater evenness and diversity, but were more homogeneous across species, whereas the GMBs of sifakas were differentiated between habitats. Thus, over relatively shallow timescales, environmental factors can override the influence of host phylogenetic placement on GMB phylogenetic composition. Moreover, feeding strategy can underlie the relative strength of host-microbiome coadaptation, with Madagascar's folivores perhaps requiring locally adapted GMBs to facilitate their highly specialized diets.}, }
@article {pmid31169073, year = {2019}, author = {Hsu, T and Gemmell, MR and Franzosa, EA and Berry, S and Mukhopadhya, I and Hansen, R and Michaud, M and Nielsen, H and Miller, WG and Nielsen, H and Bajaj-Elliott, M and Huttenhower, C and Garrett, WS and Hold, GL}, title = {Comparative genomics and genome biology of Campylobacter showae.}, journal = {Emerging microbes &amp; infections}, volume = {8}, number = {1}, pages = {827-840}, pmid = {31169073}, issn = {2222-1751}, support = {R24 DK110499/DK/NIDDK NIH HHS/United States ; }, mesh = {Bacterial Proteins/genetics ; Campylobacter/classification/*genetics/isolation &amp; purification/pathogenicity ; Campylobacter Infections/*microbiology ; Crohn Disease/microbiology ; Gastroenteritis/microbiology ; *Genome, Bacterial ; Genomics ; Humans ; Phenotype ; Phylogeny ; Virulence ; Virulence Factors/genetics ; }, abstract = {Campylobacter showae a bacterium historically linked to gingivitis and periodontitis, has recently been associated with inflammatory bowel disease and colorectal cancer. Our aim was to generate genome sequences for new clinical C. showae strains and identify functional properties explaining their pathogenic potential. Eight C. showae genomes were assessed, four strains isolated from inflamed gut tissues from paediatric Crohn's disease patients, three strains from colonic adenomas, and one from a gastroenteritis patient stool. Genome assemblies were analyzed alongside the only 3 deposited C. showae genomes. The pangenome from these 11 strains consisted of 4686 unique protein families, and the core genome size was estimated at 1050 ± 15 genes with each new genome contributing an additional 206 ± 16 genes. Functional assays indicated that colonic strains segregated into 2 groups: adherent/invasive vs. non-adherent/non-invasive strains. The former possessed Type IV secretion machinery and S-layer proteins, while the latter contained Cas genes and other CRISPR associated proteins. Comparison of gene profiles with strains in Human Microbiome Project metagenomes showed that gut-derived isolates share genes specific to tongue dorsum and supragingival plaque counterparts. Our findings indicate that C. showae strains are phenotypically and genetically diverse and suggest that secretion systems may play an important role in virulence potential.}, }
@article {pmid31167634, year = {2019}, author = {LaPierre, N and Mangul, S and Alser, M and Mandric, I and Wu, NC and Koslicki, D and Eskin, E}, title = {MiCoP: microbial community profiling method for detecting viral and fungal organisms in metagenomic samples.}, journal = {BMC genomics}, volume = {20}, number = {Suppl 5}, pages = {423}, pmid = {31167634}, issn = {1471-2164}, support = {R01 ES021801/ES/NIEHS NIH HHS/United States ; R01 MH101782/MH/NIMH NIH HHS/United States ; K25 HL080079/HL/NHLBI NIH HHS/United States ; P01 HL028481/HL/NHLBI NIH HHS/United States ; U01 DA024417/DA/NIDA NIH HHS/United States ; T32 EB016640/EB/NIBIB NIH HHS/United States ; R01 ES022282/ES/NIEHS NIH HHS/United States ; P01 HL030568/HL/NHLBI NIH HHS/United States ; R01 GM083198/GM/NIGMS NIH HHS/United States ; }, mesh = {Algorithms ; Computational Biology/*methods ; Fungi/classification/*genetics ; *Genetic Markers ; Genome, Fungal ; Genome, Viral ; High-Throughput Nucleotide Sequencing/methods ; Humans ; Metagenomics/*methods ; *Microbiota ; Sequence Analysis, DNA/*methods ; Viruses/classification/*genetics ; }, abstract = {BACKGROUND: High throughput sequencing has spurred the development of metagenomics, which involves the direct analysis of microbial communities in various environments such as soil, ocean water, and the human body. Many existing methods based on marker genes or k-mers have limited sensitivity or are too computationally demanding for many users. Additionally, most work in metagenomics has focused on bacteria and archaea, neglecting to study other key microbes such as viruses and eukaryotes.<br><br>RESULTS: Here we present a method, MiCoP (Microbiome Community Profiling), that uses fast-mapping of reads to build a comprehensive reference database of full genomes from viruses and eukaryotes to achieve maximum read usage and enable the analysis of the virome and eukaryome in each sample. We demonstrate that mapping of metagenomic reads is feasible for the smaller viral and eukaryotic reference databases. We show that our method is accurate on simulated and mock community data and identifies many more viral and fungal species than previously-reported results on real data from the Human Microbiome Project.<br><br>CONCLUSIONS: MiCoP is a mapping-based method that proves more effective than existing methods at abundance profiling of viruses and eukaryotes in metagenomic samples. MiCoP can be used to detect the full diversity of these communities. The code, data, and documentation are publicly available on GitHub at: https://github.com/smangul1/MiCoP .}, }
@article {pmid31164869, year = {2019}, author = {Belforte, FS and Fernandez, N and Tonín Monzón, F and Rosso, AD and Quesada, S and Cimolai, MC and Millán, A and Cerrone, GE and Frechtel, GD and Burcelin, R and Coluccio Leskow, F and Penas-Steinhardt, A}, title = {Getting to Know the Gut Microbial Diversity of Metropolitan Buenos Aires Inhabitants.}, journal = {Frontiers in microbiology}, volume = {10}, number = {}, pages = {965}, pmid = {31164869}, issn = {1664-302X}, support = {T37 MD001452/MD/NIMHD NIH HHS/United States ; }, abstract = {In recent years, the field of immunology has been revolutionized by the growing understanding of the fundamental role of microbiota in the immune system function. The immune system has evolved to maintain a symbiotic relationship with these microbes. The aim of our study was to know in depth the uncharacterized metagenome of the Buenos Aires (BA) city population and its metropolitan area, being the second most populated agglomeration in the southern hemisphere. For this purpose, we evaluated 30 individuals (age: 35.23 ± 8.26 years and BMI: 23.91 ± 3.4 kg/m[2]), from the general population of BA. The hypervariable regions V3-V4 of the bacterial 16S gene was sequenced by MiSeq-Illumina system, obtaining 47526 ± 4718 sequences/sample. The dominant phyla were Bacteroidetes, Firmicutes, Proteobacteria, Verrucomicrobia, and Actinobacteria. Additionally, we compared the microbiota of BA with other westernized populations (Santiago de Chile, Rosario-Argentina, United States-Human-microbiome-project, Bologna-Italy) and the Hadza population of hunter-gatherers. The unweighted UniFrac clustered together all westernized populations, leaving the hunter-gatherer population from Hadza out. In particular, Santiago de Chile's population turns out to be the closest to BA's, principally due to the presence of Verrucomicrobiales of the genus Akkermansia. These microorganisms have been proposed as a hallmark of a healthy gut. Finally, westernized populations showed more abundant metabolism related KEEG pathways than hunter-gatherers, including carbohydrate metabolism (amino sugar and nucleotide sugar metabolism), amino acid metabolism (alanine, aspartate and glutamate metabolism), lipid metabolism, biosynthesis of secondary metabolites, and sulfur metabolism. These findings contribute to promote research and comparison of the microbiome in different human populations, in order to develop more efficient therapeutic strategies for the restoration of a healthy dialogue between host and environment.}, }
@article {pmid31142868, year = {2019}, author = {}, title = {After the Integrative Human Microbiome Project, what's next for the microbiome community?.}, journal = {Nature}, volume = {569}, number = {7758}, pages = {599}, doi = {10.1038/d41586-019-01674-w}, pmid = {31142868}, issn = {1476-4687}, mesh = {Female ; Humans ; Infant, Newborn ; *Microbiota ; Pregnancy ; *Premature Birth ; Vagina ; }, }
@article {pmid31142855, year = {2019}, author = {Lloyd-Price, J and Arze, C and Ananthakrishnan, AN and Schirmer, M and Avila-Pacheco, J and Poon, TW and Andrews, E and Ajami, NJ and Bonham, KS and Brislawn, CJ and Casero, D and Courtney, H and Gonzalez, A and Graeber, TG and Hall, AB and Lake, K and Landers, CJ and Mallick, H and Plichta, DR and Prasad, M and Rahnavard, G and Sauk, J and Shungin, D and Vázquez-Baeza, Y and White, RA and ,  and Braun, J and Denson, LA and Jansson, JK and Knight, R and Kugathasan, S and McGovern, DPB and Petrosino, JF and Stappenbeck, TS and Winter, HS and Clish, CB and Franzosa, EA and Vlamakis, H and Xavier, RJ and Huttenhower, C}, title = {Multi-omics of the gut microbial ecosystem in inflammatory bowel diseases.}, journal = {Nature}, volume = {569}, number = {7758}, pages = {655-662}, pmid = {31142855}, issn = {1476-4687}, support = {U01 DK062413/DK/NIDDK NIH HHS/United States ; P30 DK043351/DK/NIDDK NIH HHS/United States ; P30 DK078392/DK/NIDDK NIH HHS/United States ; U54 DE023798/DE/NIDCR NIH HHS/United States ; R01 HG005969/HG/NHGRI NIH HHS/United States ; P01 DK046763/DK/NIDDK NIH HHS/United States ; UL1 TR001881/TR/NCATS NIH HHS/United States ; R24 DK110499/DK/NIDDK NIH HHS/United States ; U54 DK102557/DK/NIDDK NIH HHS/United States ; P30 DK040561/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Fungi/pathogenicity ; Gastrointestinal Microbiome/*genetics/immunology ; Health ; Humans ; Inflammatory Bowel Diseases/immunology/*microbiology/therapy/virology ; Phylogeny ; Species Specificity ; Transcriptome ; Viruses/pathogenicity ; }, abstract = {Inflammatory bowel diseases, which include Crohn's disease and ulcerative colitis, affect several million individuals worldwide. Crohn's disease and ulcerative colitis are complex diseases that are heterogeneous at the clinical, immunological, molecular, genetic, and microbial levels. Individual contributing factors have been the focus of extensive research. As part of the Integrative Human Microbiome Project (HMP2 or iHMP), we followed 132 subjects for one year each to generate integrated longitudinal molecular profiles of host and microbial activity during disease (up to 24 time points each; in total 2,965 stool, biopsy, and blood specimens). Here we present the results, which provide a comprehensive view of functional dysbiosis in the gut microbiome during inflammatory bowel disease activity. We demonstrate a characteristic increase in facultative anaerobes at the expense of obligate anaerobes, as well as molecular disruptions in microbial transcription (for example, among clostridia), metabolite pools (acylcarnitines, bile acids, and short-chain fatty acids), and levels of antibodies in host serum. Periods of disease activity were also marked by increases in temporal variability, with characteristic taxonomic, functional, and biochemical shifts. Finally, integrative analysis identified microbial, biochemical, and host factors central to this dysregulation. The study's infrastructure resources, results, and data, which are available through the Inflammatory Bowel Disease Multi'omics Database (http://ibdmdb.org), provide the most comprehensive description to date of host and microbial activities in inflammatory bowel diseases.}, }
@article {pmid31142853, year = {2019}, author = {, }, title = {The Integrative Human Microbiome Project.}, journal = {Nature}, volume = {569}, number = {7758}, pages = {641-648}, pmid = {31142853}, issn = {1476-4687}, support = {U54 DK102557/DK/NIDDK NIH HHS/United States ; U54 HD080784/HD/NICHD NIH HHS/United States ; U54 DK102556/DK/NIDDK NIH HHS/United States ; R01 HD092415/HD/NICHD NIH HHS/United States ; UH3 AI083263/AI/NIAID NIH HHS/United States ; U54 DE023786/DE/NIDCR NIH HHS/United States ; }, mesh = {Diet ; Female ; Gastrointestinal Microbiome/physiology ; Host Microbial Interactions/physiology ; Humans ; Infant, Newborn ; *Infant, Premature ; Infections/complications/microbiology ; Inflammatory Bowel Diseases/*microbiology ; *Microbiota/physiology ; National Institutes of Health (U.S.)/*organization &amp; administration ; Prediabetic State/complications/*microbiology ; Pregnancy ; Research/*organization &amp; administration ; Time Factors ; United States ; Vagina/microbiology ; }, abstract = {The NIH Human Microbiome Project (HMP) has been carried out over ten years and two phases to provide resources, methods, and discoveries that link interactions between humans and their microbiomes to health-related outcomes. The recently completed second phase, the Integrative Human Microbiome Project, comprised studies of dynamic changes in the microbiome and host under three conditions: pregnancy and preterm birth; inflammatory bowel diseases; and stressors that affect individuals with prediabetes. The associated research begins to elucidate mechanisms of host-microbiome interactions under these conditions, provides unique data resources (at the HMP Data Coordination Center), and represents a paradigm for future multi-omic studies of the human microbiome.}, }
@article {pmid31142849, year = {2019}, author = {Fettweis, JM and Serrano, MG and Brooks, JP and Edwards, DJ and Girerd, PH and Parikh, HI and Huang, B and Arodz, TJ and Edupuganti, L and Glascock, AL and Xu, J and Jimenez, NR and Vivadelli, SC and Fong, SS and Sheth, NU and Jean, S and Lee, V and Bokhari, YA and Lara, AM and Mistry, SD and Duckworth, RA and Bradley, SP and Koparde, VN and Orenda, XV and Milton, SH and Rozycki, SK and Matveyev, AV and Wright, ML and Huzurbazar, SV and Jackson, EM and Smirnova, E and Korlach, J and Tsai, YC and Dickinson, MR and Brooks, JL and Drake, JI and Chaffin, DO and Sexton, AL and Gravett, MG and Rubens, CE and Wijesooriya, NR and Hendricks-Muñoz, KD and Jefferson, KK and Strauss, JF and Buck, GA}, title = {The vaginal microbiome and preterm birth.}, journal = {Nature medicine}, volume = {25}, number = {6}, pages = {1012-1021}, pmid = {31142849}, issn = {1546-170X}, support = {UH2 AI083263/AI/NIAID NIH HHS/United States ; R21 HD092965/HD/NICHD NIH HHS/United States ; U54 HD080784/HD/NICHD NIH HHS/United States ; R25 GM090084/GM/NIGMS NIH HHS/United States ; R01 HD092415/HD/NICHD NIH HHS/United States ; UH3 AI083263/AI/NIAID NIH HHS/United States ; U54 DE023786/DE/NIDCR NIH HHS/United States ; }, mesh = {Adult ; Black or African American ; Biodiversity ; Cohort Studies ; Cytokines/metabolism ; Female ; Host Microbial Interactions/immunology ; Humans ; Infant, Newborn ; Inflammation Mediators/metabolism ; Longitudinal Studies ; Metagenomics ; *Microbiota/genetics/immunology ; Premature Birth/etiology/immunology/*microbiology ; Risk Factors ; United States ; Vagina/immunology/*microbiology ; Young Adult ; }, abstract = {The incidence of preterm birth exceeds 10% worldwide. There are significant disparities in the frequency of preterm birth among populations within countries, and women of African ancestry disproportionately bear the burden of risk in the United States. In the present study, we report a community resource that includes 'omics' data from approximately 12,000 samples as part of the integrative Human Microbiome Project. Longitudinal analyses of 16S ribosomal RNA, metagenomic, metatranscriptomic and cytokine profiles from 45 preterm and 90 term birth controls identified harbingers of preterm birth in this cohort of women predominantly of African ancestry. Women who delivered preterm exhibited significantly lower vaginal levels of Lactobacillus crispatus and higher levels of BVAB1, Sneathia amnii, TM7-H1, a group of Prevotella species and nine additional taxa. The first representative genomes of BVAB1 and TM7-H1 are described. Preterm-birth-associated taxa were correlated with proinflammatory cytokines in vaginal fluid. These findings highlight new opportunities for assessment of the risk of preterm birth.}, }
@article {pmid31106872, year = {2019}, author = {Hale, VL and Tan, CL and Niu, K and Yang, Y and Zhang, Q and Knight, R and Amato, KR}, title = {Gut microbiota in wild and captive Guizhou snub-nosed monkeys, Rhinopithecus brelichi.}, journal = {American journal of primatology}, volume = {81}, number = {10-11}, pages = {e22989}, doi = {10.1002/ajp.22989}, pmid = {31106872}, issn = {1098-2345}, support = {//Purdue University Andrews Fellowship/International ; //Offield Family Foundation/International ; //Earth Microbiome Project/International ; //Purdue Research Foundation Research Grant/International ; //Fanjingshan National Nature Reserve/International ; //Margot Marsh Biodiversity Foundation/International ; //San Diego Zoo Global/International ; }, mesh = {Animals ; Bacteria/classification/genetics/metabolism ; Bacterial Physiological Phenomena ; Biodiversity ; Carbohydrate Metabolism ; Colobinae/*microbiology ; Diet/*veterinary ; *Gastrointestinal Microbiome ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; }, abstract = {Many colobine species-including the endangered Guizhou snub-nosed monkey (Rhinopithecus brelichi) are difficult to maintain in captivity and frequently exhibit gastrointestinal (GI) problems. GI problems are commonly linked to alterations in the gut microbiota, which lead us to examine the gut microbial communities of wild and captive R. brelichi. We used high-throughput sequencing of the 16S rRNA gene to compare the gut microbiota of wild (N = 7) and captive (N = 8) R. brelichi. Wild monkeys exhibited increased gut microbial diversity based on the Chao1 but not Shannon diversity metric and greater relative abundances of bacteria in the Lachnospiraceae and Ruminococcaceae families. Microbes in these families digest complex plant materials and produce butyrate, a short chain fatty acid critical to colonocyte health. Captive monkeys had greater relative abundances of Prevotella and Bacteroides species, which degrade simple sugars and carbohydrates, like those present in fruits and cornmeal, two staples of the captive R. brelichi diet. Captive monkeys also had a greater abundance of Akkermansia species, a microbe that can thrive in the face of host malnutrition. Taken together, these findings suggest that poor health in captive R. brelichi may be linked to diet and an altered gut microbiota.}, }
@article {pmid31031092, year = {2019}, author = {Hull, NM and Ling, F and Pinto, AJ and Albertsen, M and Jang, HG and Hong, PY and Konstantinidis, KT and LeChevallier, M and Colwell, RR and Liu, WT}, title = {Drinking Water Microbiome Project: Is it Time?.}, journal = {Trends in microbiology}, volume = {27}, number = {8}, pages = {670-677}, doi = {10.1016/j.tim.2019.03.011}, pmid = {31031092}, issn = {1878-4380}, mesh = {Drinking Water/*microbiology ; Humans ; *Microbiota ; Water Microbiology ; }, abstract = {Now is an opportune time to foster collaborations across sectors and geographical boundaries to enable development of best practices for drinking water (DW) microbiome research, focusing on accuracy and reproducibility of meta-omic techniques (while learning from past microbiome projects). A large-scale coordinated effort that builds on this foundation will enable the urgently needed comprehensive spatiotemporal understanding and control of DW microbiomes by engineering interventions to protect public health. This opinion paper highlights the need to initiate and conduct a large-scale coordinated DW microbiome project by addressing key knowledge gaps and recommends a roadmap for this effort.}, }
@article {pmid31003081, year = {2019}, author = {Díez López, C and Vidaki, A and Ralf, A and Montiel González, D and Radjabzadeh, D and Kraaij, R and Uitterlinden, AG and Haas, C and Lao, O and Kayser, M}, title = {Novel taxonomy-independent deep learning microbiome approach allows for accurate classification of different forensically relevant human epithelial materials.}, journal = {Forensic science international. Genetics}, volume = {41}, number = {}, pages = {72-82}, doi = {10.1016/j.fsigen.2019.03.015}, pmid = {31003081}, issn = {1878-0326}, mesh = {*Deep Learning ; Female ; Forensic Genetics/methods ; *High-Throughput Nucleotide Sequencing ; Humans ; Male ; *Microbiota ; RNA, Ribosomal, 16S/*genetics ; Saliva/microbiology ; *Sequence Analysis, RNA ; Skin/microbiology ; Vagina/microbiology ; }, abstract = {Correct identification of different human epithelial materials such as from skin, saliva and vaginal origin is relevant in forensic casework as it provides crucial information for crime reconstruction. However, the overlap in human cell type composition between these three epithelial materials provides challenges for their differentiation and identification when using previously proposed human cell biomarkers, while their microbiota composition largely differs. By using validated 16S rRNA gene massively parallel sequencing data from the Human Microbiome Project of 1636 skin, oral and vaginal samples, 50 taxonomy-independent deep learning networks were trained to classify these three tissues. Validation testing was performed in de-novo generated high-throughput 16S rRNA gene sequencing data using the Ion Torrent[™] Personal Genome Machine from 110 test samples: 56 hand skin, 31 saliva and 23 vaginal secretion specimens. Body-site classification accuracy of these test samples was very high as indicated by AUC values of 0.99 for skin, 0.99 for oral, and 1 for vaginal secretion. Misclassifications were limited to 3 (5%) skin samples. Additional forensic validation testing was performed in mock casework samples by de-novo high-throughput sequencing of 19 freshly-prepared samples and 22 samples aged for 1 up to 7.6 years. All of the 19 fresh and 20 (91%) of the 22 aged mock casework samples were correctly tissue-type classified. Moreover, comparing the microbiome results with outcomes from previous human mRNA-based tissue identification testing in the same 16 aged mock casework samples reveals that our microbiome approach performs better in 12 (75%), similarly in 2 (12.5%), and less good in 2 (12.5%) of the samples. Our results demonstrate that this new microbiome approach allows for accurate tissue-type classification of three human epithelial materials of skin, oral and vaginal origin, which is highly relevant for future forensic investigations.}, }
@article {pmid30997937, year = {2019}, author = {Clayton, JB and Shields-Cutler, RR and Hoops, SL and Al-Ghalith, GA and Sha, JCM and Johnson, TJ and Knights, D}, title = {Bacterial community structure and function distinguish gut sites in captive red-shanked doucs (Pygathrix nemaeus).}, journal = {American journal of primatology}, volume = {81}, number = {10-11}, pages = {e22977}, pmid = {30997937}, issn = {1098-2345}, support = {T32 DA007097/DA/NIDA NIH HHS/United States ; //Margot Marsh Biodiversity Foundation/International ; }, mesh = {Animals ; Bacteria/*classification/genetics ; Biodiversity ; Colobinae/*microbiology ; Feces/microbiology ; *Gastrointestinal Microbiome ; Genome, Bacterial ; Intestines/microbiology/physiology ; Sequence Analysis, DNA ; Stomach/microbiology/physiology ; }, abstract = {The mammalian order primates contains wide species diversity. Members of the subfamily Colobinae are unique amongst extant primates in that their gastrointestinal systems more closely resemble those of ruminants than other members of the primate order. In the growing literature surrounding nonhuman primate microbiomes, analysis of microbial communities has been limited to the hindgut, since few studies have captured data on other gut sites, including the foregut of colobine primates. In this study, we used the red-shanked douc (Pygathrix nemaeus) as a model for colobine primates to study the relationship between gastrointestinal bacterial community structure and gut site within and between subjects. We analyzed fecal and pregastric stomach content samples, representative of the hindgut and foregut respectively, using 16S recombinant DNA (rDNA) sequencing and identified microbiota using closed-reference operational taxonomic unit (OTU) picking against the GreenGenes database. Our results show divergent bacterial communities clearly distinguish the foregut and hindgut microbiomes. We found higher bacterial biodiversity and a higher Firmicutes:Bacteroides ratio in the hindgut as opposed to the foregut. These gut sites showed strong associations with bacterial function. Specifically, energy metabolism was upregulated in the hindgut, whereas detoxification was increased in the foregut. Our results suggest a red-shanked douc's foregut microbiome is no more concordant with its own hindgut than it is with any other red-shanked douc's hindgut microbiome, thus reinforcing the notion that the bacterial communities of the foregut and hindgut are distinctly unique. OPEN PRACTICES: This article has been awarded Open Materials and Open Data badges. All materials and data are publicly accessible via the IRIS Repository at https://www.iris-database.org/iris/app/home/detail?id=york:934328. Learn more about the Open Practices badges from the Center for Open Science: https://osf.io/tvyxz/wiki.}, }
@article {pmid30981803, year = {2019}, author = {Parida, S and Sharma, D}, title = {The power of small changes: Comprehensive analyses of microbial dysbiosis in breast cancer.}, journal = {Biochimica et biophysica acta. Reviews on cancer}, volume = {1871}, number = {2}, pages = {392-405}, pmid = {30981803}, issn = {1879-2561}, support = {R01 CA204555/CA/NCI NIH HHS/United States ; R01 CA204555/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Breast Neoplasms/*microbiology ; *Dysbiosis ; Female ; Humans ; }, abstract = {Disparate occurrence of breast cancer remains an intriguing question since only a subset of women with known risk factors develop cancer. Recent studies suggest an active role of local and distant microbiota in breast cancer initiation, progression, and overall prognosis. A dysbiotic microbiota predisposes the body to develop cancer by inducing genetic instability, initiating DNA damage and proliferation of the damaged progeny, eliciting favorable immune response, metabolic dysregulation and altered response to therapy. In this review, we present our analyses of the existing datasets and discuss the local dysbiosis observed in breast cancer patients and different aspects of breast carcinogenesis that can be potentially influenced by local breast microbiota. Striking differences between microbial community compositions in breast of cancer patients compared to healthy individuals were noted. Differences in microbiome were also apparent between benign and malignant disease and between nipple aspirate fluid of healthy individuals and breast survivors. We also discuss the identification of distinct bacterial, fungal, viral as well as parasite signatures for breast cancer. These microbes are capable of producing numerous secondary metabolites that can act as signaling mediators effecting breast cancer progression. We review how microbes potentially alter response to therapy affecting drug metabolism, pharmacokinetics, anti-tumor effects and toxicity. In conclusion, breast harbors a community of microbes that can communicate with the host cells inducing downstream signaling pathways and modulating various aspects of breast cancer growth and metastatic progression and an improved understanding of microbial dysbiosis can potentially reduce breast cancer risk and improve outcomes of breast cancer patients. The human microbiome, now referred to as, the "forgotten organ" contains a metagenome that is 100-fold more diverse compared to the human genome, thereby, is critically associated with human health [1,2]. With the revelations of the human microbiome project and advent of deep sequencing techniques, a plethora of information has been acquired in recent years. Body sites like stomach, bladder and lungs, once thought to be sterile, are now known to harbor millions of indigenous microbial species. Approximately 80% of the healthy microbiome consists of Firmicutes and Bacteroidetes accompanied by Verrucomicrobia, Actinobacteria, Proteobacteria, Tenericutes and Cyanobacteria [2-7]. The role of microbiome in diabetes, obesity and even neurodegenerative diseases was greatly appreciated in the last decade [1,7-14] and now it has been established that microbiome significantly contributes to many organ specific cancers [1,15,16].}, }
@article {pmid30976019, year = {2019}, author = {Jeong, H and Arif, B and Caetano-Anollés, G and Kim, KM and Nasir, A}, title = {Horizontal gene transfer in human-associated microorganisms inferred by phylogenetic reconstruction and reconciliation.}, journal = {Scientific reports}, volume = {9}, number = {1}, pages = {5953}, pmid = {30976019}, issn = {2045-2322}, mesh = {Bacteria/classification/*genetics/isolation &amp; purification ; Computational Biology/*methods ; Evolution, Molecular ; *Gene Transfer, Horizontal ; *Genes, Bacterial ; *Genome, Bacterial ; Humans ; Models, Genetic ; *Phylogeny ; }, abstract = {Horizontal gene transfer (HGT) is widespread in the evolution of prokaryotes, especially those associated with the human body. Here, we implemented large-scale gene-species phylogenetic tree reconstructions and reconciliations to identify putative HGT-derived genes in the reference genomes of microbiota isolated from six major human body sites by the NIH Human Microbiome Project. Comparisons with a control group representing microbial genomes from diverse natural environments indicated that HGT activity increased significantly in the genomes of human microbiota, which is confirmatory of previous findings. Roughly, more than half of total genes in the genomes of human-associated microbiota were transferred (donated or received) by HGT. Up to 60% of the detected HGTs occurred either prior to the colonization of the human body or involved bacteria residing in different body sites. The latter could suggest 'genetic crosstalk' and movement of bacterial genes within the human body via hitherto poorly understood mechanisms. We also observed that HGT activity increased significantly among closely-related microorganisms and especially when they were united by physical proximity, suggesting that the 'phylogenetic effect' can significantly boost HGT activity. Finally, we identified several core and widespread genes least influenced by HGT that could become useful markers for building robust 'trees of life' and address several outstanding technical challenges to improve the phylogeny-based genome-wide HGT detection method for future applications.}, }
@article {pmid30973913, year = {2019}, author = {Pinto, D and Sorbellini, E and Marzani, B and Rucco, M and Giuliani, G and Rinaldi, F}, title = {Scalp bacterial shift in Alopecia areata.}, journal = {PloS one}, volume = {14}, number = {4}, pages = {e0215206}, pmid = {30973913}, issn = {1932-6203}, mesh = {Adult ; Alopecia Areata/complications/*microbiology ; Case-Control Studies ; DNA, Bacterial/genetics/isolation &amp; purification ; Dysbiosis/complications/*microbiology ; Female ; Humans ; Male ; Microbiota/genetics ; Middle Aged ; Propionibacterium/isolation &amp; purification ; Scalp/*microbiology ; Staphylococcus aureus/isolation &amp; purification ; Staphylococcus epidermidis/isolation &amp; purification ; Young Adult ; }, abstract = {The role of microbial dysbiosis in scalp disease has been recently hypothesized. However, little information is available with regards to the association between microbial population on the scalp and hair diseases related to hair growth. Here we investigated bacterial communities in healthy and Alopecia areata (AA) subjects. The analysis of bacterial distribution at the genus level highlighted an increase of Propionibacterium in AA subjects alongside a general decrease of Staphylococcus. Analysis of log Relative abundance of main bacterial species inhabiting the scalp showed a significant increase of Propionibacterium acnes in AA subjects compared to control ones. AA scalp condition is also associated with a significant decrease of Staphylococcus epidermidis relative abundance. No significant changes were found for Staphylococcus aureus. Therefore, data from sequencing profiling of the bacterial population strongly support a different microbial composition of the different area surrounded hair follicle from the epidermis to hypodermis, highlighting differences between normal and AA affected the scalp. Our results highlight, for the first time, the presence of a microbial shift on the scalp of patients suffering from AA and gives the basis for a larger and more complete study of microbial population involvement in hair disorders.}, }
@article {pmid30942867, year = {2019}, author = {Brown, SM and Chen, H and Hao, Y and Laungani, BP and Ali, TA and Dong, C and Lijeron, C and Kim, B and Wultsch, C and Pei, Z and Krampis, K}, title = {MGS-Fast: Metagenomic shotgun data fast annotation using microbial gene catalogs.}, journal = {GigaScience}, volume = {8}, number = {4}, pages = {}, pmid = {30942867}, issn = {2047-217X}, support = {UH3 CA140233/CA/NCI NIH HHS/United States ; UL1 TR000457/TR/NCATS NIH HHS/United States ; G12 MD007599/MD/NIMHD NIH HHS/United States ; R01 AI110372/AI/NIAID NIH HHS/United States ; U54 CA221705/CA/NCI NIH HHS/United States ; UL1 TR002384/TR/NCATS NIH HHS/United States ; R01 CA159036/CA/NCI NIH HHS/United States ; R21 DE025352/DE/NIDCR NIH HHS/United States ; U01 CA182370/CA/NCI NIH HHS/United States ; }, mesh = {Algorithms ; Cloud Computing ; Computational Biology/*methods ; Humans ; Metagenome ; Metagenomics/*methods ; Microbiology ; Microbiota ; Molecular Sequence Annotation ; Reproducibility of Results ; *Software ; Workflow ; }, abstract = {BACKGROUND: Current methods used for annotating metagenomics shotgun sequencing (MGS) data rely on a computationally intensive and low-stringency approach of mapping each read to a generic database of proteins or reference microbial genomes.<br><br>RESULTS: We developed MGS-Fast, an analysis approach for shotgun whole-genome metagenomic data utilizing Bowtie2 DNA-DNA alignment of reads that is an alternative to using the integrated catalog of reference genes database of well-annotated genes compiled from human microbiome data. This method is rapid and provides high-stringency matches (>90% DNA sequence identity) of the metagenomics reads to genes with annotated functions. We demonstrate the use of this method with data from a study of liver disease and synthetic reads, and Human Microbiome Project shotgun data, to detect differentially abundant Kyoto Encyclopedia of Genes and Genomes gene functions in these experiments. This rapid annotation method is freely available as a Galaxy workflow within a Docker image.<br><br>CONCLUSIONS: MGS-Fast can confidently transfer functional annotations from gene databases to metagenomic reads, with speed and accuracy.}, }
@article {pmid30937887, year = {2019}, author = {Sharma, A and Buschmann, MM and Gilbert, JA}, title = {Pharmacomicrobiomics: The Holy Grail to Variability in Drug Response?.}, journal = {Clinical pharmacology and therapeutics}, volume = {106}, number = {2}, pages = {317-328}, doi = {10.1002/cpt.1437}, pmid = {30937887}, issn = {1532-6535}, mesh = {*Host Microbial Interactions/drug effects/physiology ; Humans ; *Microbiota/drug effects/physiology ; Pharmaceutical Preparations/*metabolism ; *Pharmacogenetics ; Systems Biology ; }, abstract = {The human body, with 3.0 × 10[13] cells and more than 3.8 × 10[13] microorganisms, has nearly a one-to-one ratio of resident microbes to human cells. Initiatives like the Human Microbiome Project, American Gut, and Flemish Gut have identified associations between microbial taxa and human health. The study of interactions between microbiome and pharmaceutical agents, i.e., pharmacomicrobiomics, has revealed an instrumental role of the microbiome in modulating drug response that alters the therapeutic outcomes. In this review, we present our current comprehension of the relationship of the microbiome, host biology, and pharmaceutical agents such as cardiovascular drugs, analgesics, and chemotherapeutic agents to human disease and treatment outcomes. We also discuss the significance of studying diet-gene-drug interactions and further address the key challenges associated with pharmacomicrobiomics. Finally, we examine proposed models employing systems biology for the application of pharmacomicrobiomics and other -omics data, and provide approaches to elucidate microbiome-drug interactions to improve future translation to personalized medicine.}, }
@article {pmid30932230, year = {2019}, author = {Greene, LK and Bornbusch, SL and McKenney, EA and Harris, RL and Gorvetzian, SR and Yoder, AD and Drea, CM}, title = {The importance of scale in comparative microbiome research: New insights from the gut and glands of captive and wild lemurs.}, journal = {American journal of primatology}, volume = {81}, number = {10-11}, pages = {e22974}, doi = {10.1002/ajp.22974}, pmid = {30932230}, issn = {1098-2345}, support = {//Duke University/International ; //Margot Marsh Biodiversity Foundation/International ; //Duke Lemur Center/International ; S10 OD018164/OD/NIH HHS/United States ; 1749465//Division of Behavioral and Cognitive Sciences/International ; 1749898//Division of Behavioral and Cognitive Sciences/International ; }, mesh = {Animal Husbandry ; Animals ; Diet/veterinary ; *Feeding Behavior ; Female ; Gastrointestinal Microbiome ; Host Microbial Interactions ; Lemuridae/*microbiology ; Madagascar ; Male ; *Microbiota ; Phylogeny ; Scent Glands/*microbiology ; }, abstract = {Research on animal microbiomes is increasingly aimed at determining the evolutionary and ecological factors that govern host-microbiome dynamics, which are invariably intertwined and potentially synergistic. We present three empirical studies related to this topic, each of which relies on the diversity of Malagasy lemurs (representing a total of 19 species) and the comparative approach applied across scales of analysis. In Study 1, we compare gut microbial membership across 14 species in the wild to test the relative importance of host phylogeny and feeding strategy in mediating microbiome structure. Whereas host phylogeny strongly predicted community composition, the same feeding strategies shared by distant relatives did not produce convergent microbial consortia, but rather shaped microbiomes in host lineage-specific ways, particularly in folivores. In Study 2, we compare 14 species of wild and captive folivores, frugivores, and omnivores, to highlight the importance of captive populations for advancing gut microbiome research. We show that the perturbational effect of captivity is mediated by host feeding strategy and can be mitigated, in part, by modified animal management. In Study 3, we examine various scent-gland microbiomes across three species in the wild or captivity and show them to vary by host species, sex, body site, and a proxy of social status. These rare data provide support for the bacterial fermentation hypothesis in olfactory signal production and implicate steroid hormones as mediators of microbial community structure. We conclude by discussing the role of scale in comparative microbial studies, the links between feeding strategy and host-microbiome coadaptation, the underappreciated benefits of captive populations for advancing conservation research, and the need to consider the entirety of an animal's microbiota. Ultimately, these studies will help move the field from exploratory to hypothesis-driven research.}, }
@article {pmid30919073, year = {2019}, author = {Ames, NJ and Barb, JJ and Ranucci, A and Kim, H and Mudra, SE and Cashion, AK and Townsley, DM and Childs, R and Paster, BJ and Faller, LL and Wallen, GR}, title = {The oral microbiome of patients undergoing treatment for severe aplastic anemia: a pilot study.}, journal = {Annals of hematology}, volume = {98}, number = {6}, pages = {1351-1365}, doi = {10.1007/s00277-019-03599-w}, pmid = {30919073}, issn = {1432-0584}, mesh = {Adult ; Aged ; Anemia, Aplastic/drug therapy/*microbiology/therapy ; Anti-Bacterial Agents/pharmacology ; Antilymphocyte Serum/therapeutic use ; Benzoates/pharmacology/therapeutic use ; Biodiversity ; Cyclosporine/therapeutic use ; DNA, Bacterial/analysis ; Dental Health Surveys ; Female ; Graft vs Host Disease/etiology/microbiology ; Hematopoietic Stem Cell Transplantation ; Humans ; Hydrazines/pharmacology/therapeutic use ; Immunocompromised Host ; Immunosuppressive Agents/therapeutic use ; Male ; *Microbiota/drug effects ; Middle Aged ; Mouth/*microbiology ; Pilot Projects ; Pyrazoles/pharmacology/therapeutic use ; Ribotyping ; Sequence Analysis, DNA ; Smoking/epidemiology ; T-Lymphocytes/immunology ; Tongue/microbiology ; Young Adult ; }, abstract = {The microbiome, an intriguing component of the human body, composed of trillions of microorganisms, has prompted scientific exploration to identify and understand its function and role in health and disease. As associations between microbiome composition, disease, and symptoms accumulate, the future of medicine hinges upon a comprehensive knowledge of these microorganisms for patient care. The oral microbiome may provide valuable and efficient insight for predicting future changes in disease status, infection, or treatment course. The main aim of this pilot study was to characterize the oral microbiome in patients with severe aplastic anemia (SAA) during their therapeutic course. SAA is a hematologic disease characterized by bone marrow failure which if untreated is fatal. Treatment includes either hematopoietic stem cell transplantation (HSCT) or immunosuppressive therapy (IST). In this study, we examined the oral microbiome composition of 24 patients admitted to the National Institutes of Health (NIH) Clinical Center for experimental SAA treatment. Tongue brushings were collected to assess the effects of treatment on the oral microbiome. Twenty patients received standard IST (equine antithymocyte globulin and cyclosporine) plus eltrombopag. Four patients underwent HSCT. Oral specimens were obtained at three time points during treatment and clinical follow-up. Using a novel approach to 16S rRNA gene sequence analysis encompassing seven hypervariable regions, results demonstrated a predictable decrease in microbial diversity over time among the transplant patients. Linear discriminant analysis or LefSe reported a total of 14 statistically significant taxa (p < 0.05) across time points in the HSCT patients. One-way plots of relative abundance for two bacterial species (Haemophilus parainfluenzae and Rothia mucilaginosa) in the HSCT group, show the differences in abundance between time points. Only one bacterial species (Prevotella histicola) was noted in the IST group with a p value of 0.065. The patients receiving immunosuppressive therapy did not exhibit a clear change in diversity over time; however, patient-specific changes were noted. In addition, we compared our findings to tongue dorsum samples from healthy participants in the Human Microbiome Project (HMP) database and found among HSCT patients, approximately 35% of bacterial identifiers (N = 229) were unique to this study population and were not present in tongue dorsum specimens obtained from the HMP. Among IST-treated patients, 45% (N = 351) were unique to these patients and not identified by the HMP. Although antibiotic use may have likely influenced bacterial composition and diversity, some literature suggests a decreased impact of antimicrobials on the oral microbiome as compared to their effect on the gut microbiome. Future studies with larger sample sizes that focus on the oral microbiome and the effects of antibiotics in an immunosuppressed patient population may help establish these potential associations.}, }
@article {pmid30858577, year = {2019}, author = {Cabana, F and Clayton, JB and Nekaris, KAI and Wirdateti, W and Knights, D and Seedorf, H}, title = {Nutrient-based diet modifications impact on the gut microbiome of the Javan slow loris (Nycticebus javanicus).}, journal = {Scientific reports}, volume = {9}, number = {1}, pages = {4078}, pmid = {30858577}, issn = {2045-2322}, mesh = {Animals ; Animals, Wild ; Animals, Zoo ; Bacteroides/classification/drug effects/isolation &amp; purification ; Bifidobacterium/classification/drug effects/isolation &amp; purification ; *Diet ; Gastrointestinal Microbiome/drug effects/*genetics ; Lorisidae/microbiology/*physiology ; Nutrients/*pharmacology ; Prevotella/classification/drug effects/isolation &amp; purification ; Primates/genetics ; }, abstract = {Environment and diet are key factors which shape the microbiome of organisms. There is also a disparity between captive and wild animals of the same species, presumably because of the change in diet. Being able to reverse the microbiome to the wild type is thus particularly important for the reintroduction efforts of Critically Endangered animals. The Javan slow loris (Nycticebus javanicus) is a suitable model, being kept in the thousands within rescue centres throughout Southeast Asia. With next-generation sequencing, we show how a naturalistic diet impacts the gut microbiome of captive slow lorises (Primates: Nycticebus). A comparison of the microbiome of wild animals with captive animals that had been fed a standard captive or improved diet reveals strong microbiome differences between wild and captive animals; however, diet changes failed to alter the microbiome of captive populations significantly. Bifidobacterium was the most abundant genus in wild animals (46.7%) while Bacteroides (11.6%) and Prevotella (18.9%) were the most abundant in captive animals fed the captive and improved diets, respectively. Correlation analyses of nutrients with microbial taxa suggest important implications in using nutrition to suppress potential pathogens, with soluble fibre and water-soluble carbohydrates both being associated with opposing microbiome profiles. The improved diet significantly increased microbe diversity, which exemplifies the importance of high fibre diets; however, wild individuals had lower diversity, which contradicts recent studies. Detection of methanogens appeared to be dependent on diet and whether the animals were living in captivity or in the wild. This study highlights the potential of nutrition in modulating the microbiome of animals prior to release. Unexpectedly, the results were not as significant as has been suggested in recent studies.}, }
@article {pmid30832730, year = {2019}, author = {Meyer, F and Bremges, A and Belmann, P and Janssen, S and McHardy, AC and Koslicki, D}, title = {Assessing taxonomic metagenome profilers with OPAL.}, journal = {Genome biology}, volume = {20}, number = {1}, pages = {51}, pmid = {30832730}, issn = {1474-760X}, mesh = {Classification/methods ; Humans ; Metagenomics/methods/*standards ; *Software ; }, abstract = {The explosive growth in taxonomic metagenome profiling methods over the past years has created a need for systematic comparisons using relevant performance criteria. The Open-community Profiling Assessment tooL (OPAL) implements commonly used performance metrics, including those of the first challenge of the initiative for the Critical Assessment of Metagenome Interpretation (CAMI), together with convenient visualizations. In addition, we perform in-depth performance comparisons with seven profilers on datasets of CAMI and the Human Microbiome Project. OPAL is freely available at https://github.com/CAMI-challenge/OPAL .}, }
@article {pmid30814984, year = {2019}, author = {Song, Z and Wang, X and Zhou, X and Jiang, S and Li, Y and Ahmad, O and Qi, L and Li, P and Li, J}, title = {Taxonomic Distribution of FosB in Human-Microbiota and Activity Comparison of Fosfomycin Resistance.}, journal = {Frontiers in microbiology}, volume = {10}, number = {}, pages = {200}, pmid = {30814984}, issn = {1664-302X}, abstract = {FosB, a Mg[2+] dependent thioltransferase, confers antibiotic resistance to fosfomycin through enzymatic drug inactivation. Among all antibiotic resistant proteins in the Antibiotic Resistance Genes Database and the Comprehensive Antibiotic Resistance Database, FosB is within 5% of the most number of ARPs identified in Human Microbiome Project reference database but mainly distributed in limited genera, i.e., 122 of total 133 FosB homologues are found from Bacillus and Staphylococcus. Furthermore, these FosB sequences could be divided into three clusters based on their phylogenetic relationship, i.e., two groups of FosB were mainly from Bacillus, and another was mainly from Staphylococcus. Finally, we confirmed that FosB from the group of Staphylococcus presented the highest resistance ability to fosfomycin by in silico and in vitro comparisons. In summary, this study elaborates the specific taxonomic characteristics and resistant abilities of FosB in human microbiota, which might help in developing more promising fosfomycin-like antibiotics.}, }
@article {pmid30808411, year = {2019}, author = {, }, title = {A review of 10 years of human microbiome research activities at the US National Institutes of Health, Fiscal Years 2007-2016.}, journal = {Microbiome}, volume = {7}, number = {1}, pages = {31}, pmid = {30808411}, issn = {2049-2618}, mesh = {Biomedical Research/*economics/*organization &amp; administration ; Humans ; Metagenomics/economics/organization &amp; administration ; Microbiota ; National Institutes of Health (U.S.) ; United States ; }, abstract = {The National Institutes of Health (NIH) is the primary federal government agency for biomedical research in the USA. NIH provides extensive support for human microbiome research with 21 of 27 NIH Institutes and Centers (ICs) currently funding this area through their extramural research programs. This analysis of the NIH extramural portfolio in human microbiome research briefly reviews the early history of this field at NIH, summarizes the program objectives and the resources developed in the recently completed 10-year (fiscal years 2007-2016) $215 M Human Microbiome Project (HMP) program, evaluates the scope and range of the $728 M NIH investment in extramural human microbiome research activities outside of the HMP over fiscal years 2012-2016, and highlights some specific areas of research which emerged from this investment. This analysis closes with a few comments on the technical needs and knowledge gaps which remain for this field to be able to advance over the next decade and for the outcomes of this research to be able to progress to microbiome-based interventions for treating disease and supporting health.}, }
@article {pmid30808401, year = {2019}, author = {, }, title = {2017 NIH-wide workshop report on "The Human Microbiome: Emerging Themes at the Horizon of the 21st Century".}, journal = {Microbiome}, volume = {7}, number = {1}, pages = {32}, pmid = {30808401}, issn = {2049-2618}, support = {U54 DE023789/DE/NIDCR NIH HHS/United States ; U54 DK102557/DK/NIDDK NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; P30 CA014236/CA/NCI NIH HHS/United States ; U54 HD080784/HD/NICHD NIH HHS/United States ; R24 DK110499/DK/NIDDK NIH HHS/United States ; }, mesh = {Humans ; Internet ; *Microbiota ; National Institutes of Health (U.S.) ; United States ; }, abstract = {The National Institutes of Health (NIH) organized a three-day human microbiome research workshop, August 16-18, 2017, to highlight the accomplishments of the 10-year Human Microbiome Project program, the outcomes of the investments made by the 21 NIH Institutes and Centers which now fund this area, and the technical challenges and knowledge gaps which will need to be addressed in order for this field to advance over the next 10 years. This report summarizes the key points in the talks, round table discussions, and Joint Agency Panel from this workshop.}, }
@article {pmid30718869, year = {2019}, author = {Forster, SC and Kumar, N and Anonye, BO and Almeida, A and Viciani, E and Stares, MD and Dunn, M and Mkandawire, TT and Zhu, A and Shao, Y and Pike, LJ and Louie, T and Browne, HP and Mitchell, AL and Neville, BA and Finn, RD and Lawley, TD}, title = {A human gut bacterial genome and culture collection for improved metagenomic analyses.}, journal = {Nature biotechnology}, volume = {37}, number = {2}, pages = {186-192}, pmid = {30718869}, issn = {1546-1696}, support = {/WT_/Wellcome Trust/United Kingdom ; 098051/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Bacteria/classification ; Computational Biology/methods ; Contig Mapping ; Gastrointestinal Microbiome ; *Genome, Bacterial ; Genome, Human ; Humans ; *Metagenome ; *Metagenomics ; Phylogeny ; RNA, Ribosomal, 16S/metabolism ; Sequence Analysis, DNA ; Species Specificity ; }, abstract = {Understanding gut microbiome functions requires cultivated bacteria for experimental validation and reference bacterial genome sequences to interpret metagenome datasets and guide functional analyses. We present the Human Gastrointestinal Bacteria Culture Collection (HBC), a comprehensive set of 737 whole-genome-sequenced bacterial isolates, representing 273 species (105 novel species) from 31 families found in the human gastrointestinal microbiota. The HBC increases the number of bacterial genomes derived from human gastrointestinal microbiota by 37%. The resulting global Human Gastrointestinal Bacteria Genome Collection (HGG) classifies 83% of genera by abundance across 13,490 shotgun-sequenced metagenomic samples, improves taxonomic classification by 61% compared to the Human Microbiome Project (HMP) genome collection and achieves subspecies-level classification for almost 50% of sequences. The improved resource of gastrointestinal bacterial reference sequences circumvents dependence on de novo assembly of metagenomes and enables accurate and cost-effective shotgun metagenomic analyses of human gastrointestinal microbiota.}, }
@article {pmid30705670, year = {2018}, author = {Whittle, E and Leonard, MO and Harrison, R and Gant, TW and Tonge, DP}, title = {Multi-Method Characterization of the Human Circulating Microbiome.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {3266}, pmid = {30705670}, issn = {1664-302X}, abstract = {The term microbiome describes the genetic material encoding the various microbial populations that inhabit our body. Whilst colonization of various body niches (e.g., the gut) by dynamic communities of microorganisms is now universally accepted, the existence of microbial populations in other "classically sterile" locations, including the blood, is a relatively new concept. The presence of bacteria-specific DNA in the blood has been reported in the literature for some time, yet the true origin of this is still the subject of much deliberation. The aim of this study was to investigate the phenomenon of a "blood microbiome" by providing a comprehensive description of bacterially derived nucleic acids using a range of complementary molecular and classical microbiological techniques. For this purpose we utilized a set of plasma samples from healthy subjects (n = 5) and asthmatic subjects (n = 5). DNA-level analyses involved the amplification and sequencing of the 16S rRNA gene. RNA-level analyses were based upon the de novo assembly of unmapped mRNA reads and subsequent taxonomic identification. Molecular studies were complemented by viability data from classical aerobic and anaerobic microbial culture experiments. At the phylum level, the blood microbiome was predominated by Proteobacteria, Actinobacteria, Firmicutes, and Bacteroidetes. The key phyla detected were consistent irrespective of molecular method (DNA vs. RNA), and consistent with the results of other published studies. In silico comparison of our data with that of the Human Microbiome Project revealed that members of the blood microbiome were most likely to have originated from the oral or skin communities. To our surprise, aerobic and anaerobic cultures were positive in eight of out the ten donor samples investigated, and we reflect upon their source. Our data provide further evidence of a core blood microbiome, and provide insight into the potential source of the bacterial DNA/RNA detected in the blood. Further, data reveal the importance of robust experimental procedures, and identify areas for future consideration.}, }
@article {pmid30658055, year = {2019}, author = {Pellock, SJ and Walton, WG and Ervin, SM and Torres-Rivera, D and Creekmore, BC and Bergan, G and Dunn, ZD and Li, B and Tripathy, A and Redinbo, MR}, title = {Discovery and Characterization of FMN-Binding β-Glucuronidases in the Human Gut Microbiome.}, journal = {Journal of molecular biology}, volume = {431}, number = {5}, pages = {970-980}, pmid = {30658055}, issn = {1089-8638}, support = {P30 ES010126/ES/NIEHS NIH HHS/United States ; T32 GM008570/GM/NIGMS NIH HHS/United States ; R01 CA161879/CA/NCI NIH HHS/United States ; R01 CA207416/CA/NCI NIH HHS/United States ; R01 CA098468/CA/NCI NIH HHS/United States ; }, mesh = {Catalytic Domain/physiology ; Clostridiales/metabolism ; Flavin Mononucleotide/*metabolism ; Gastrointestinal Microbiome/*physiology ; Glucuronidase/*metabolism ; Humans ; Kinetics ; Metagenome/physiology ; Microbiota/physiology ; Ruminococcus/metabolism ; }, abstract = {The human gut microbiota encodes β-glucuronidases (GUSs) that play key roles in health and disease via the metabolism of glucuronate-containing carbohydrates and drugs. Hundreds of putative bacterial GUS enzymes have been identified by metagenomic analysis of the human gut microbiome, but less than 10% have characterized structures and functions. Here we describe a set of unique gut microbial GUS enzymes that bind flavin mononucleotide (FMN). First, we show using mass spectrometry, isothermal titration calorimetry, and x-ray crystallography that a purified GUS from the gut commensal microbe Faecalibacterium prausnitzii binds to FMN on a surface groove located 30 Å away from the active site. Second, utilizing structural and functional data from this FMN-binding GUS, we analyzed the 279 unique GUS sequences from the Human Microbiome Project database and identified 14 putative FMN-binding GUSs. We characterized four of these hits and solved the structure of two, the GUSs from Ruminococcus gnavus and Roseburia hominis, which confirmed that these are FMN binders. Third, binding and kinetic analysis of the FMN-binding site mutants of these five GUSs show that they utilize a conserved site to bind FMN that is not essential for GUS activity, but can affect KM. Lastly, a comprehensive structural review of the PDB reveals that the FMN-binding site employed by these enzymes is unlike any structurally characterized FMN binders to date. These findings reveal the first instance of an FMN-binding glycoside hydrolase and suggest a potential link between FMN and carbohydrate metabolism in the human gut microbiota.}, }
@article {pmid30649168, year = {2019}, author = {Griffith, JC and Morgan, XC}, title = {Invited Commentary: Improving the Accessibility of Human Microbiome Project Data Through Integration With R/Bioconductor.}, journal = {American journal of epidemiology}, volume = {188}, number = {6}, pages = {1027-1030}, doi = {10.1093/aje/kwz007}, pmid = {30649168}, issn = {1476-6256}, mesh = {Computational Biology ; Humans ; Metagenome ; *Microbiota ; Phylogeny ; RNA, Ribosomal, 16S ; }, abstract = {Alterations in the composition of the microbiota have been implicated in many diseases. The Human Microbiome Project (HMP) provides a comprehensive reference data set of the "normal" human microbiome of 242 healthy adults at 5 major body sites. The HMP used both 16S ribosomal RNA gene sequencing and whole-genome metagenomic sequencing to profile the subjects' microbial communities. However, accessing and analyzing the HMP data set still presents technical and bioinformatic challenges, given that researchers must import the microbiome data, integrate phylogenetic trees, and access and merge public and restricted metadata. The HMP16SData R/Bioconductor package developed by Schiffer et al. (Am J Epidemiol. 2019;188(6):1023-1026) greatly simplifies access to the HMP data by combining 16S taxonomic abundance data, public patient metadata, and phylogenetic trees as a single data object. The authors also provide an interface for users with approved Database of Genotypes and Phenotypes (dbGaP) projects to easily retrieve and merge the controlled-access HMP metadata. This package has a broad range of appeal to researchers across disciplines and with various levels of expertise in using R and/or other statistical tools, which translates to improved data accessibility for public health research, with data from healthy individuals serving as a reference for disease-associated studies.}, }
@article {pmid30649166, year = {2019}, author = {Schiffer, L and Azhar, R and Shepherd, L and Ramos, M and Geistlinger, L and Huttenhower, C and Dowd, JB and Segata, N and Waldron, L}, title = {HMP16SData: Efficient Access to the Human Microbiome Project Through Bioconductor.}, journal = {American journal of epidemiology}, volume = {188}, number = {6}, pages = {1023-1026}, pmid = {30649166}, issn = {1476-6256}, support = {R01 HG005220/HG/NHGRI NIH HHS/United States ; R21 AI121784/AI/NIAID NIH HHS/United States ; U24 CA180996/CA/NCI NIH HHS/United States ; U54 DE023798/DE/NIDCR NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Computational Biology ; Databases, Genetic/*statistics &amp; numerical data ; Female ; Humans ; Male ; Microbiota/*physiology ; RNA, Ribosomal, 16S/*metabolism ; Young Adult ; }, abstract = {Phase 1 of the Human Microbiome Project (HMP) investigated 18 body subsites of 242 healthy American adults to produce the first comprehensive reference for the composition and variation of the "healthy" human microbiome. Publicly available data sets from amplicon sequencing of two 16S ribosomal RNA variable regions, with extensive controlled-access participant data, provide a reference for ongoing microbiome studies. However, utilization of these data sets can be hindered by the complex bioinformatic steps required to access, import, decrypt, and merge the various components in formats suitable for ecological and statistical analysis. The HMP16SData package provides count data for both 16S ribosomal RNA variable regions, integrated with phylogeny, taxonomy, public participant data, and controlled participant data for authorized researchers, using standard integrative Bioconductor data objects. By removing bioinformatic hurdles of data access and management, HMP16SData enables epidemiologists with only basic R skills to quickly analyze HMP data.}, }
@article {pmid30637337, year = {2018}, author = {Bayer, K and Jahn, MT and Slaby, BM and Moitinho-Silva, L and Hentschel, U}, title = {Marine Sponges as Chloroflexi Hot Spots: Genomic Insights and High-Resolution Visualization of an Abundant and Diverse Symbiotic Clade.}, journal = {mSystems}, volume = {3}, number = {6}, pages = {}, pmid = {30637337}, issn = {2379-5077}, abstract = {Members of the widespread bacterial phylum Chloroflexi can dominate high-microbial-abundance (HMA) sponge microbiomes. In the Sponge Microbiome Project, Chloroflexi sequences amounted to 20 to 30% of the total microbiome of certain HMA sponge genera with the classes/clades SAR202, Caldilineae, and Anaerolineae being the most prominent. We performed metagenomic and single-cell genomic analyses to elucidate the functional gene repertoire of Chloroflexi symbionts of Aplysina aerophoba. Eighteen draft genomes were reconstructed and placed into phylogenetic context of which six were investigated in detail. Common genomic features of Chloroflexi sponge symbionts were related to central energy and carbon converting pathways, amino acid and fatty acid metabolism, and respiration. Clade-specific metabolic features included a massively expanded genomic repertoire for carbohydrate degradation in Anaerolineae and Caldilineae genomes, but only amino acid utilization by SAR202. While Anaerolineae and Caldilineae import cofactors and vitamins, SAR202 genomes harbor genes encoding components involved in cofactor biosynthesis. A number of features relevant to symbiosis were further identified, including CRISPR-Cas systems, eukaryote-like repeat proteins, and secondary metabolite gene clusters. Chloroflexi symbionts were visualized in the sponge extracellular matrix at ultrastructural resolution by the fluorescence in situ hybridization-correlative light and electron microscopy (FISH-CLEM) method. Carbohydrate degradation potential was reported previously for "Candidatus Poribacteria" and SAUL, typical symbionts of HMA sponges, and we propose here that HMA sponge symbionts collectively engage in degradation of dissolved organic matter, both labile and recalcitrant. Thus, sponge microbes may not only provide nutrients to the sponge host, but they may also contribute to dissolved organic matter (DOM) recycling and primary productivity in reef ecosystems via a pathway termed the sponge loop. IMPORTANCE Chloroflexi represent a widespread, yet enigmatic bacterial phylum with few cultivated members. We used metagenomic and single-cell genomic approaches to characterize the functional gene repertoire of Chloroflexi symbionts in marine sponges. The results of this study suggest clade-specific metabolic specialization and that Chloroflexi symbionts have the genomic potential for dissolved organic matter (DOM) degradation from seawater. Considering the abundance and dominance of sponges in many benthic environments, we predict that the role of sponge symbionts in biogeochemical cycles is larger than previously thought.}, }
@article {pmid30623484, year = {2019}, author = {Zhai, J and Knox, K and Twigg, HL and Zhou, H and Zhou, JJ}, title = {Exact variance component tests for longitudinal microbiome studies.}, journal = {Genetic epidemiology}, volume = {43}, number = {3}, pages = {250-262}, pmid = {30623484}, issn = {1098-2272}, support = {R01 GM105785/GM/NIGMS NIH HHS/United States ; P30 ES006694/ES/NIEHS NIH HHS/United States ; R01 HG006139/HG/NHGRI NIH HHS/United States ; U01 HL098960/HL/NHLBI NIH HHS/United States ; HG006139/HG/NHGRI NIH HHS/United States ; K01DK106116/DK/NIDDK NIH HHS/United States ; GM053275/GM/NIGMS NIH HHS/United States ; GM105785/GM/NIGMS NIH HHS/United States ; K01 DK106116/DK/NIDDK NIH HHS/United States ; R01 GM053275/GM/NIGMS NIH HHS/United States ; U01 HL121831/HL/NHLBI NIH HHS/United States ; }, mesh = {Computer Simulation ; Humans ; Longitudinal Studies ; Lung/microbiology ; *Microbiota ; *Models, Genetic ; }, abstract = {In metagenomic studies, testing the association between microbiome composition and clinical outcomes translates to testing the nullity of variance components. Motivated by a lung human immunodeficiency virus (HIV) microbiome project, we study longitudinal microbiome data by using variance component models with more than two variance components. Current testing strategies only apply to models with exactly two variance components and when sample sizes are large. Therefore, they are not applicable to longitudinal microbiome studies. In this paper, we propose exact tests (score test, likelihood ratio test, and restricted likelihood ratio test) to (a) test the association of the overall microbiome composition in a longitudinal design and (b) detect the association of one specific microbiome cluster while adjusting for the effects from related clusters. Our approach combines the exact tests for null hypothesis with a single variance component with a strategy of reducing multiple variance components to a single one. Simulation studies demonstrate that our method has a correct type I error rate and superior power compared to existing methods at small sample sizes and weak signals. Finally, we apply our method to a longitudinal pulmonary microbiome study of HIV-infected patients and reveal two interesting genera Prevotella and Veillonella associated with forced vital capacity. Our findings shed light on the impact of the lung microbiome on HIV complexities. The method is implemented in the open-source, high-performance computing language Julia and is freely available at https://github.com/JingZhai63/VCmicrobiome.}, }
@article {pmid32422014, year = {2019}, author = {Lambring, CB and Siraj, S and Patel, K and Sankpal, UT and Mathew, S and Basha, R}, title = {Impact of the Microbiome on the Immune System.}, journal = {Critical reviews in immunology}, volume = {39}, number = {5}, pages = {313-328}, pmid = {32422014}, issn = {1040-8401}, support = {P20 CA233355/CA/NCI NIH HHS/United States ; R25 HL125447/HL/NHLBI NIH HHS/United States ; S21 MD012472/MD/NIMHD NIH HHS/United States ; U54 MD006882/MD/NIMHD NIH HHS/United States ; }, mesh = {Animals ; Autoimmune Diseases/*immunology/microbiology ; Host-Pathogen Interactions ; Humans ; Immune System/immunology/*microbiology ; Immunity ; Infections/*immunology/microbiology ; Metabolic Diseases/*immunology/microbiology ; Microbiota/immunology ; Neoplasms/*immunology/microbiology ; }, abstract = {Higher organisms are all born with general immunity as well as with, increasingly, more specific immune systems. All immune mechanisms function with the intent of aiding the body in defense against infection. Internal and external factors alike have varying effects on the immune system, and the immune response is tailored specifically to each one. Accompanying the components of the human innate and adaptive immune systems are the other intermingling systems of the human body. Increasing understanding of the body's immune interactions with other systems has opened new avenues of study, including that of the microbiome. The microbiome has become a highly active area of research over the last 10 to 20 years since the NIH began funding the Human Microbiome Project (HMP), which was established in 2007. Several publications have focused on the characterization, functions, and complex interplay of the microbiome as it relates to the rest of the body. A dysfunction between the microbiome and the host has been linked to various diseases including cancers, metabolic deficiencies, autoimmune disorders, and infectious diseases. Further understanding of the microbiome and its interaction with the host in relation to diseases is needed in order to understand the implications of microbiome dysfunction and the possible use of microbiota in the prevention of disease. In this review, we have summarized information on the immune system, the microbiome, the microbiome's interplay with other systems, and the association of the immune system and the microbiome in diseases such as diabetes and colorectal cancer.}, }
@article {pmid30578265, year = {2019}, author = {Stubbendieck, RM and May, DS and Chevrette, MG and Temkin, MI and Wendt-Pienkowski, E and Cagnazzo, J and Carlson, CM and Gern, JE and Currie, CR}, title = {Competition among Nasal Bacteria Suggests a Role for Siderophore-Mediated Interactions in Shaping the Human Nasal Microbiota.}, journal = {Applied and environmental microbiology}, volume = {85}, number = {10}, pages = {}, pmid = {30578265}, issn = {1098-5336}, support = {P01 HL070831/HL/NHLBI NIH HHS/United States ; T15 LM007359/LM/NLM NIH HHS/United States ; T32 GM008505/GM/NIGMS NIH HHS/United States ; U19 AI109673/AI/NIAID NIH HHS/United States ; }, mesh = {Actinobacteria/*physiology ; Humans ; Microbiota/*physiology ; Nasal Cavity/*microbiology ; Siderophores/*metabolism ; Staphylococcus/*physiology ; }, abstract = {Resources available in the human nasal cavity are limited. Therefore, to successfully colonize the nasal cavity, bacteria must compete for scarce nutrients. Competition may occur directly through interference (e.g., antibiotics) or indirectly by nutrient sequestration. To investigate the nature of nasal bacterial competition, we performed coculture inhibition assays between nasal Actinobacteria and Staphylococcus spp. We found that isolates of coagulase-negative staphylococci (CoNS) were sensitive to growth inhibition by Actinobacteria but that Staphylococcus aureus isolates were resistant to inhibition. Among Actinobacteria, we observed that Corynebacterium spp. were variable in their ability to inhibit CoNS. We sequenced the genomes of 10 Corynebacterium species isolates, including 3 Corynebacterium propinquum isolates that strongly inhibited CoNS and 7 other Corynebacterium species isolates that only weakly inhibited CoNS. Using a comparative genomics approach, we found that the C. propinquum genomes were enriched in genes for iron acquisition and harbored a biosynthetic gene cluster (BGC) for siderophore production, absent in the noninhibitory Corynebacterium species genomes. Using a chrome azurol S assay, we confirmed that C. propinquum produced siderophores. We demonstrated that iron supplementation rescued CoNS from inhibition by C. propinquum, suggesting that inhibition was due to iron restriction through siderophore production. Through comparative metabolomics and molecular networking, we identified the siderophore produced by C. propinquum as dehydroxynocardamine. Finally, we confirmed that the dehydroxynocardamine BGC is expressed in vivo by analyzing human nasal metatranscriptomes from the NIH Human Microbiome Project. Together, our results suggest that bacteria produce siderophores to compete for limited available iron in the nasal cavity and improve their fitness.IMPORTANCE Within the nasal cavity, interference competition through antimicrobial production is prevalent. For instance, nasal Staphylococcus species strains can inhibit the growth of other bacteria through the production of nonribosomal peptides and ribosomally synthesized and posttranslationally modified peptides. In contrast, bacteria engaging in exploitation competition modify the external environment to prevent competitors from growing, usually by hindering access to or depleting essential nutrients. As the nasal cavity is a nutrient-limited environment, we hypothesized that exploitation competition occurs in this system. We determined that Corynebacterium propinquum produces an iron-chelating siderophore, and this iron-sequestering molecule correlates with the ability to inhibit the growth of coagulase-negative staphylococci. Furthermore, we found that the genes required for siderophore production are expressed in vivo Thus, although siderophore production by bacteria is often considered a virulence trait, our work indicates that bacteria may produce siderophores to compete for limited iron in the human nasal cavity.}, }
@article {pmid30559213, year = {2018}, author = {Tedijanto, C and Olesen, SW and Grad, YH and Lipsitch, M}, title = {Estimating the proportion of bystander selection for antibiotic resistance among potentially pathogenic bacterial flora.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {51}, pages = {E11988-E11995}, pmid = {30559213}, issn = {1091-6490}, support = {R01 AI132606/AI/NIAID NIH HHS/United States ; U01 CK000538/CK/NCEZID CDC HHS/United States ; U01CK000538//ACL HHS/United States ; U54 GM088558/GM/NIGMS NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Anti-Bacterial Agents/immunology/*pharmacology ; Bacteria/classification/*drug effects/immunology ; Child ; Child, Preschool ; Drug Resistance, Bacterial/*drug effects/immunology ; Escherichia coli/drug effects ; Humans ; Infant ; Infant, Newborn ; Microbial Sensitivity Tests/methods ; Microbiota/*drug effects/immunology ; Pneumococcal Infections ; Pneumococcal Vaccines/immunology ; Species Specificity ; Staphylococcus aureus/drug effects ; Streptococcus pneumoniae/drug effects ; United States ; Vaccination ; Vaccines, Conjugate/immunology ; Young Adult ; }, abstract = {Bystander selection-the selective pressure for resistance exerted by antibiotics on microbes that are not the target pathogen of treatment-is critical to understanding the total impact of broad-spectrum antibiotic use on pathogenic bacterial species that are often carried asymptomatically. However, to our knowledge, this effect has never been quantified. We quantify bystander selection for resistance for a range of clinically relevant antibiotic-species pairs as the proportion of all antibiotic exposures received by a species for conditions in which that species was not the causative pathogen ("proportion of bystander exposures"). Data sources include the 2010-2011 National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey, the Human Microbiome Project, and additional carriage and etiological data from existing literature. For outpatient prescribing in the United States, we find that this proportion over all included antibiotic classes is over 80% for eight of nine organisms of interest. Low proportions of bystander exposure are often associated with infrequent bacterial carriage or concentrated prescribing of a particular antibiotic for conditions caused by the species of interest. Applying our results, we roughly estimate that pneumococcal conjugate vaccination programs result in nearly the same proportional reduction in total antibiotic exposures of Streptococcus pneumoniae, Staphylococcus aureus, and Escherichia coli, despite the latter two organisms not being targeted by the vaccine. These results underscore the importance of considering antibiotic exposures of bystanders, in addition to the target pathogen, in measuring the impact of antibiotic resistance interventions.}, }
@article {pmid30536921, year = {2019}, author = {Clayton, JB and Danzeisen, JL and Johnson, TJ and Trent, AM and Hayer, SS and Murphy, T and Wuenschmann, A and Elder, M and Shen, Z and Mannion, A and Bryant, E and Knights, D and Fox, JG}, title = {Characterization of Campylobacter jejuni, Campylobacter upsaliensis, and a novel Campylobacter sp. in a captive non-human primate zoological collection.}, journal = {Journal of medical primatology}, volume = {48}, number = {2}, pages = {114-122}, pmid = {30536921}, issn = {1600-0684}, support = {R01 OD011141/OD/NIH HHS/United States ; T32 DA007097/DA/NIDA NIH HHS/United States ; P30 ES002109/ES/NIEHS NIH HHS/United States ; T32 OD010978/OD/NIH HHS/United States ; }, mesh = {Animals ; Animals, Zoo ; Ape Diseases/*epidemiology/microbiology ; Campylobacter/*isolation &amp; purification ; Campylobacter Infections/epidemiology/microbiology/*veterinary ; Campylobacter jejuni/isolation &amp; purification ; Campylobacter upsaliensis/isolation &amp; purification ; Female ; Haplorhini ; Hominidae ; Male ; Minnesota/epidemiology ; Monkey Diseases/*epidemiology/microbiology ; Phylogeny ; Prevalence ; RNA, Bacterial/analysis ; RNA, Ribosomal, 16S/analysis ; Species Specificity ; }, abstract = {BACKGROUND: The aim of this study was to longitudinally investigate the prevalence and characterization of Campylobacter spp. from non-human primates primate (NHP) with a history of endemic diarrhea housed at Como Park Zoo.<br><br>METHODS: Fecal samples from 33 symptom-free NHP belonging to eight different species were collected weekly for 9&#xa0;weeks. Species-level characterization and phylogenetic analysis of isolates included biochemical testing and 16S rRNA sequencing.<br><br>RESULTS: Campylobacter spp. were isolated from the feces of 42% (14/33) of the primates. Three Campylobacter spp. (C&#xa0;upsaliensis, C&#xa0;jejuni, and novel Campylobacter sp.) were identified from three NHP species. A possible positive host Campylobacter species-specificity was observed. However, no statistical association was observed between the isolation of Campylobacter spp. and age and sex of the animal.<br><br>CONCLUSIONS: The study revealed the value of conducting repeated fecal sampling to establish the overall prevalence of Campylobacter in zoo-maintained NHP; it also importantly identifies a novel Campylobacter sp. isolated from white-faced saki monkeys.}, }
@article {pmid30534599, year = {2018}, author = {Escapa, IF and Chen, T and Huang, Y and Gajare, P and Dewhirst, FE and Lemon, KP}, title = {New Insights into Human Nostril Microbiome from the Expanded Human Oral Microbiome Database (eHOMD): a Resource for the Microbiome of the Human Aerodigestive Tract.}, journal = {mSystems}, volume = {3}, number = {6}, pages = {}, pmid = {30534599}, issn = {2379-5077}, support = {R01 AI101018/AI/NIAID NIH HHS/United States ; R01 DE024468/DE/NIDCR NIH HHS/United States ; R01 DE016937/DE/NIDCR NIH HHS/United States ; R37 DE016937/DE/NIDCR NIH HHS/United States ; UL1 TR001102/TR/NCATS NIH HHS/United States ; R01 GM117174/GM/NIGMS NIH HHS/United States ; }, abstract = {The expanded Human Oral Microbiome Database (eHOMD) is a comprehensive microbiome database for sites along the human aerodigestive tract that revealed new insights into the nostril microbiome. The eHOMD provides well-curated 16S rRNA gene reference sequences linked to available genomes and enables assignment of species-level taxonomy to most next-generation sequences derived from diverse aerodigestive tract sites, including the nasal passages, sinuses, throat, esophagus, and mouth. Using minimum entropy decomposition coupled with the RDP Classifier and our eHOMD V1-V3 training set, we reanalyzed 16S rRNA V1-V3 sequences from the nostrils of 210 Human Microbiome Project participants at the species level, revealing four key insights. First, we discovered that Lawsonella clevelandensis, a recently named bacterium, and Neisseriaceae [G-1] HMT-174, a previously unrecognized bacterium, are common in adult nostrils. Second, just 19 species accounted for 90% of the total sequences from all participants. Third, 1 of these 19 species belonged to a currently uncultivated genus. Fourth, for 94% of the participants, 2 to 10 species constituted 90% of their sequences, indicating that the nostril microbiome may be represented by limited consortia. These insights highlight the strengths of the nostril microbiome as a model system for studying interspecies interactions and microbiome function. Also, in this cohort, three common nasal species (Dolosigranulum pigrum and two Corynebacterium species) showed positive differential abundance when the pathobiont Staphylococcus aureus was absent, generating hypotheses regarding colonization resistance. By facilitating species-level taxonomic assignment to microbes from the human aerodigestive tract, the eHOMD is a vital resource enhancing clinical relevance of microbiome studies. IMPORTANCE The eHOMD (http://www.ehomd.org) is a valuable resource for researchers, from basic to clinical, who study the microbiomes and the individual microbes in body sites in the human aerodigestive tract, which includes the nasal passages, sinuses, throat, esophagus, and mouth, and the lower respiratory tract, in health and disease. The eHOMD is an actively curated, web-based, open-access resource. eHOMD provides the following: (i) species-level taxonomy based on grouping 16S rRNA gene sequences at 98.5% identity, (ii) a systematic naming scheme for unnamed and/or uncultivated microbial taxa, (iii) reference genomes to facilitate metagenomic, metatranscriptomic, and proteomic studies and (iv) convenient cross-links to other databases (e.g., PubMed and Entrez). By facilitating the assignment of species names to sequences, the eHOMD is a vital resource for enhancing the clinical relevance of 16S rRNA gene-based microbiome studies, as well as metagenomic studies.}, }
@article {pmid30521034, year = {2018}, author = {Moitinho-Silva, L and Nielsen, S and Amir, A and Gonzalez, A and Ackermann, GL and Cerrano, C and Astudillo-Garcia, C and Easson, C and Sipkema, D and Liu, F and Steinert, G and Kotoulas, G and McCormack, GP and Feng, G and Bell, JJ and Vicente, J and Björk, JR and Montoya, JM and Olson, JB and Reveillaud, J and Steindler, L and Pineda, MC and Marra, MV and Ilan, M and Taylor, MW and Polymenakou, P and Erwin, PM and Schupp, PJ and Simister, RL and Knight, R and Thacker, RW and Costa, R and Hill, RT and Lopez-Legentil, S and Dailianis, T and Ravasi, T and Hentschel, U and Li, Z and Webster, NS and Thomas, T}, title = {Erratum to: The sponge microbiome project.}, journal = {GigaScience}, volume = {7}, number = {12}, pages = {}, doi = {10.1093/gigascience/giy145}, pmid = {30521034}, issn = {2047-217X}, }
@article {pmid30510919, year = {2018}, author = {Brenner, LA and Hoisington, AJ and Stearns-Yoder, KA and Stamper, CE and Heinze, JD and Postolache, TT and Hadidi, DA and Hoffmire, CA and Stanislawski, MA and Lowry, CA}, title = {Military-Related Exposures, Social Determinants of Health, and Dysbiosis: The United States-Veteran Microbiome Project (US-VMP).}, journal = {Frontiers in cellular and infection microbiology}, volume = {8}, number = {}, pages = {400}, pmid = {30510919}, issn = {2235-2988}, mesh = {Adult ; Aged ; Cohort Studies ; *Dysbiosis ; Female ; Humans ; Male ; Mental Health ; *Microbiota ; Middle Aged ; Military Personnel/*psychology ; *Social Determinants of Health ; United States ; United States Department of Veterans Affairs ; Veterans ; *Veterans Health ; Young Adult ; }, abstract = {Significant effort has been put forth to increase understanding regarding the role of the human microbiome in health- and disease-related processes. In turn, the United States (US) Veteran Microbiome Project (US-VMP) was conceptualized as a means by which to serially collect microbiome and health-related data from those seeking care within the Veterans Health Administration (VHA). In this manuscript, exposures related to military experiences, as well as conditions and health-related factors among patients seen in VHA clinical settings are discussed in relation to common psychological and physical outcomes. Upon enrollment in the study, Veterans complete psychometrically sound (i.e., reliable and valid) measures regarding their past and current medical history. Participants also provide skin, oral, and gut microbiome samples, and permission to track their health status via the VHA electronic medical record. To date, data collection efforts have been cross-diagnostic. Within this manuscript, we describe current data collection practices and procedures, as well as highlight demographic, military, and psychiatric characteristics of the first 188 Veterans enrolled in the study. Based on these findings, we assert that this cohort is unique as compared to those enrolled in recent large-scale studies of the microbiome. To increase understanding regarding disease and health among diverse cohorts, efforts such as the US-VMP are vital. Ongoing barriers and facilitators to data collection are discussed, as well as future research directions, with an emphasis on the importance of shifting current thinking regarding the microbiome from a focus on normalcy and dysbiosis to health promotion and disease prevention.}, }
@article {pmid30481125, year = {2018}, author = {Kim, JW and Lee, JS and Kim, JH and Jeong, JW and Lee, DH and Nam, S}, title = {Comparison of Microbiota Variation in Korean Healthy Adolescents with Adults Suggests Notable Maturity Differences.}, journal = {Omics : a journal of integrative biology}, volume = {22}, number = {12}, pages = {770-778}, pmid = {30481125}, issn = {1557-8100}, mesh = {Adolescent ; Gastrointestinal Microbiome/*genetics ; Humans ; Microbiota/*genetics ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, RNA/methods ; }, abstract = {Comparative studies of microbiome variation in world populations and different developmental stages of organisms are essential to decipher the linkages among microbiome, health, and disease. Notably, the gut microbiota are believed to mature in early life. In this context, we compared the gut microbiota diversity in Korean adolescent healthy samples (KAHSs) to healthy Korean adults (HKAs) as well as the Human Microbiome Project healthy samples (HMPHSs), the latter being one of the largest adult cohorts, based on organismal composition, alpha- and beta-diversities, function/pathway prediction analysis, and co-occurrence networks. We found that the gut microbiota compositions, including the ratios of firmicutes to bacteroidetes, between KAHSs and HMPHSs were different, and the diversities of KAHSs were less than those of HMPHSs. The predicted functions, for example, secondary bile acid synthesis and insulin signaling of KAHSs and HMPHSs, were also significantly different. Genus-level networks showed that co-occurrences among different taxa more frequently happened in HMPHSs than in KAHSs. Even though both KAHSs and HMPHSs represent healthy microbiomes, comparisons showed substantial differences, likely implicating different diets, environments, and demographics. Interestingly, we observed lower microbial diversities and less frequent co-occurrences among different taxa in KAHSs than adult HMPHSs and HKAs. These new findings collectively suggest that the adolescent gut microbiota in the present Korean sample did not reach the extent of maturity of adult microbiota diversity. In all, further population studies of microbiome variation across geographies and developmental stages are warranted, and should usefully inform future diagnostics and therapeutics innovation targeting the microbiome.}, }
@article {pmid30465353, year = {2018}, author = {Wang, H and Kang, D and Zhou, XD and Li, YQ}, title = {[Prevention of infectious diseases through microecology modulation techniques].}, journal = {Hua xi kou qiang yi xue za zhi = Huaxi kouqiang yixue zazhi = West China journal of stomatology}, volume = {36}, number = {5}, pages = {564-567}, pmid = {30465353}, issn = {2618-0456}, mesh = {Humans ; *Microbiota ; Mouth/microbiology ; Skin/microbiology ; }, abstract = {The microbe is small in volume, but large in quantity and species. The symbiotic microbe, which is far more than human cells, code millions times of genes than human being. Somatic cells and these symbiotic microbe distributing in human body skin, respiratory tract, oral cavity and gastrointestinal tract, urinary tract and other parts form a complex ecosystem whose dynamic balance is highly related to body health. With the successful implementation of Human Microbiome Project, more attentions have been paid to the next generation microbiome technologies. New tools and methods for ecological regulation of human microbiome are emerging. The way we improve the world of human microbiology will be more convenient. This paper will make a review on the modulation techniques of human microbiome.}, }
@article {pmid30452039, year = {2019}, author = {Rajakovich, LJ and Balskus, EP}, title = {Metabolic functions of the human gut microbiota: the role of metalloenzymes.}, journal = {Natural product reports}, volume = {36}, number = {4}, pages = {593-625}, pmid = {30452039}, issn = {1460-4752}, mesh = {Ammonia/metabolism ; Cresols/metabolism ; Enzymes/chemistry/*metabolism ; Gastrointestinal Microbiome/*physiology ; Host-Pathogen Interactions/immunology/*physiology ; Humans ; Hydrogen Sulfide/metabolism ; Metals/chemistry/metabolism ; Methylamines/metabolism ; Nucleoside Q/biosynthesis ; Polysaccharides/metabolism ; Vitamins/biosynthesis ; Xenobiotics/pharmacokinetics ; }, abstract = {Covering: up to the end of 2017 The human body is composed of an equal number of human and microbial cells. While the microbial community inhabiting the human gastrointestinal tract plays an essential role in host health, these organisms have also been connected to various diseases. Yet, the gut microbial functions that modulate host biology are not well established. In this review, we describe metabolic functions of the human gut microbiota that involve metalloenzymes. These activities enable gut microbial colonization, mediate interactions with the host, and impact human health and disease. We highlight cases in which enzyme characterization has advanced our understanding of the gut microbiota and examples that illustrate the diverse ways in which metalloenzymes facilitate both essential and unique functions of this community. Finally, we analyze Human Microbiome Project sequencing datasets to assess the distribution of a prominent family of metalloenzymes in human-associated microbial communities, guiding future enzyme characterization efforts.}, }
@article {pmid30425147, year = {2018}, author = {Su, X and Jing, G and McDonald, D and Wang, H and Wang, Z and Gonzalez, A and Sun, Z and Huang, S and Navas, J and Knight, R and Xu, J}, title = {Identifying and Predicting Novelty in Microbiome Studies.}, journal = {mBio}, volume = {9}, number = {6}, pages = {}, pmid = {30425147}, issn = {2150-7511}, mesh = {*Computational Biology ; *Databases, Factual ; Humans ; Microbiota/*genetics ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; }, abstract = {With the expansion of microbiome sequencing globally, a key challenge is to relate new microbiome samples to the existing space of microbiome samples. Here, we present Microbiome Search Engine (MSE), which enables the rapid search of query microbiome samples against a large, well-curated reference microbiome database organized by taxonomic similarity at the whole-microbiome level. Tracking the microbiome novelty score (MNS) over 8 years of microbiome depositions based on searching in more than 100,000 global 16S rRNA gene amplicon samples, we detected that the structural novelty of human microbiomes is approaching saturation and likely bounded, whereas that in environmental habitats remains 5 times higher. Via the microbiome focus index (MFI), which is derived from the MNS and microbiome attention score (MAS), we objectively track and compare the structural-novelty and attracted-attention scores of individual microbiome samples and projects, and we predict future trends in the field. For example, marine and indoor environments and mother-baby interactions are likely to receive disproportionate additional attention based on recent trends. Therefore, MNS, MAS, and MFI are proposed "alt-metrics" for evaluating a microbiome project or prospective developments in the microbiome field, both of which are done in the context of existing microbiome big data.IMPORTANCE We introduce two concepts to quantify the novelty of a microbiome. The first, the microbiome novelty score (MNS), allows identification of microbiomes that are especially different from what is already sequenced. The second, the microbiome attention score (MAS), allows identification of microbiomes that have many close neighbors, implying that considerable scientific attention is devoted to their study. By computing a microbiome focus index based on the MNS and MAS, we objectively track and compare the novelty and attention scores of individual microbiome samples and projects over time and predict future trends in the field; i.e., we work toward yielding fundamentally new microbiomes rather than filling in the details. Therefore, MNS, MAS, and MFI can serve as "alt-metrics" for evaluating a microbiome project or prospective developments in the microbiome field, both of which are done in the context of existing microbiome big data.}, }
@article {pmid30423063, year = {2018}, author = {Frioux, C and Fremy, E and Trottier, C and Siegel, A}, title = {Scalable and exhaustive screening of metabolic functions carried out by microbial consortia.}, journal = {Bioinformatics (Oxford, England)}, volume = {34}, number = {17}, pages = {i934-i943}, pmid = {30423063}, issn = {1367-4811}, mesh = {Humans ; *Microbial Consortia ; Microbiota ; Software ; }, abstract = {MOTIVATION: The selection of species exhibiting metabolic behaviors of interest is a challenging step when switching from the investigation of a large microbiota to the study of functions effectiveness. Approaches based on a compartmentalized framework are not scalable. The output of scalable approaches based on a non-compartmentalized modeling may be so large that it has neither been explored nor handled so far.<br><br>RESULTS: We present the Miscoto tool to facilitate the selection of a community optimizing a desired function in a microbiome by reporting several possibilities which can be then sorted according to biological criteria. Communities are exhaustively identified using logical programming and by combining the non-compartmentalized and the compartmentalized frameworks. The benchmarking of 4.9 million metabolic functions associated with the Human Microbiome Project, shows that Miscoto is suited to screen and classify metabolic producibility in terms of feasibility, functional redundancy and cooperation processes involved. As an illustration of a host-microbial system, screening the Recon 2.2 human metabolism highlights the role of different consortia within a family of 773 intestinal bacteria.<br><br>Miscoto source code, instructions for use and examples are available at: https://github.com/cfrioux/miscoto.}, }
@article {pmid30419494, year = {2019}, author = {Ventura Spagnolo, E and Stassi, C and Mondello, C and Zerbo, S and Milone, L and Argo, A}, title = {Forensic microbiology applications: A systematic review.}, journal = {Legal medicine (Tokyo, Japan)}, volume = {36}, number = {}, pages = {73-80}, doi = {10.1016/j.legalmed.2018.11.002}, pmid = {30419494}, issn = {1873-4162}, mesh = {Adult ; Aged ; Body Fluids/*microbiology ; Brain/*microbiology ; Cause of Death ; Databases, Bibliographic ; Digestive System/*microbiology ; Female ; *Forensic Medicine ; Heart/*microbiology ; Humans ; Male ; *Microbiota ; Middle Aged ; *Postmortem Changes ; Skin/*microbiology ; Time Factors ; }, abstract = {According to the Human Microbiome Project (HMP), a healthy human body contains ten times more microbes than human cells. Microbial communities colonize different organs of the body, playing fundamental roles both in human health and disease. Despite the vast scientific knowledge of the role of microbial communities in a living body, little is known at present about microbial changes occurring after death, thus leading many authors to investigate the composition of the thanatomicrobiome and its potential applications in the forensic field. The aim of the following review is to provide a general overview of the advances of postmortem microbiology research, mainly focusing on the role of microbiological investigations carried out on internal organs and fluids. To this end, a total of 19 studies have been sistematically reviewed, each one chosen according to specific inclusion/exclusion criteria. The selected studies assess the contribution of contamination, postmortem transmigration and agonal spread to microbial isolation from dead body samples, and shed light on the role of postmortem microbiological investigations in several forensic fields, such as cause of death or PMI determination.}, }
@article {pmid30400268, year = {2018}, author = {Ojo-Okunola, A and Nicol, M and du Toit, E}, title = {Human Breast Milk Bacteriome in Health and Disease.}, journal = {Nutrients}, volume = {10}, number = {11}, pages = {}, pmid = {30400268}, issn = {2072-6643}, support = {U01 AI110466/AI/NIAID NIH HHS/United States ; 1U01AI110466-01A1//H3Africa U01 AWARD FROM THE NATIONAL INSTITUTES OF HEALTH OF THE USA/ ; U54HG009824//NIH Office of the Director/ ; OPP1017641; OPP1017579//Bill and Melinda Gates Foundation/ ; U54 HG009824/HG/NHGRI NIH HHS/United States ; }, mesh = {Bacteria/isolation &amp; purification ; Feces/microbiology ; Female ; HIV Infections/microbiology/therapy ; Humans ; Infant ; Mastitis/microbiology/therapy ; *Microbiota ; Milk, Human/*microbiology ; Neoplasms/microbiology/therapy ; }, abstract = {It is well-known that, beyond nutritional components, human breast milk (HBM) contains a wide variety of non-nutritive bio-factors perfectly suited for the growing infant. In the pre-2000 era, HBM was considered sterile and devoid of micro-organisms. Though HBM was not included as part of the human microbiome project launched in 2007, great strides have been made in studying the bacterial diversity of HBM in both a healthy state and diseased state, and in understanding their role in infant health. HBM provides a vast array of beneficial micro-organisms that play a key role in colonizing the infant's mucosal system, including that of the gut. They also have a role in priming the infant's immune system and supporting its maturation. In this review, we provide an in-depth and updated insight into the immunomodulatory, metabolic, and anti-infective role of HBM bacteriome (bacterial community) and its effect on infant health. We also provide key information from the literature by exploring the possible origin of microbial communities in HBM, the bacterial diversity in this niche and the determinants influencing the HBM bacteriome. Lastly, we investigate the role of the HBM bacteriome in maternal infectious disease (human immunodeficiency virus (HIV) and mastitis)), and cancer. Key gaps in HBM bacterial research are also identified.}, }
@article {pmid30397444, year = {2018}, author = {Ma, ZS}, title = {DAR (diversity-area relationship): Extending classic SAR (species-area relationship) for biodiversity and biogeography analyses.}, journal = {Ecology and evolution}, volume = {8}, number = {20}, pages = {10023-10038}, pmid = {30397444}, issn = {2045-7758}, abstract = {I extend the classic SAR, which has achieved status of ecological law and plays a critical role in global biodiversity and biogeography analyses, to general DAR (diversity-area relationship). The extension was aimed to remedy a serious application limitation of the traditional SAR that only addressed one aspect of biodiversity scaling-species richness scaling over space, but ignoring species abundance information. The extension was further inspired by a recent consensus that Hill numbers offer the most appropriate measures for alpha-diversity and multiplicative beta-diversity. In particular, Hill numbers are essentially a series of Renyi's entropy values weighted differently along the rare-common-dominant spectrum of species abundance distribution and are in the units of effective number of species (or species equivalents such as OTUs). I therefore postulate that Hill numbers should follow the same or similar law of the traditional SAR. I test the postulation with the American gut microbiome project (AGP) dataset of 1,473 healthy North American individuals. I further propose three new concepts and develop their statistical estimation formulae based on the new DAR extension, including: (i) DAR profile-z-q relationship (DAR scaling parameter z at different diversity order q), (ii) PDO (pair-wise diversity overlap) profile-g-q relationship (PDO parameter g at order q, and (iii) MAD (maximal accrual diversity: D max) profile-D max-q. While the classic SAR is a special case of our new DAR profile, the PDO and MAD profiles offer novel tools for analyzing biodiversity (including alpha-diversity and beta-diversity) and biogeography over space.}, }
@article {pmid30367598, year = {2018}, author = {Shi, JY and Huang, H and Zhang, YN and Cao, JB and Yiu, SM}, title = {BMCMDA: a novel model for predicting human microbe-disease associations via binary matrix completion.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 9}, pages = {281}, pmid = {30367598}, issn = {1471-2105}, support = {R03 AA016008/AA/NIAAA NIH HHS/United States ; }, mesh = {*Algorithms ; *Bacteria ; Bacterial Physiological Phenomena ; Computational Biology/*methods ; *Disease ; Host-Pathogen Interactions ; Humans ; *Microbiota ; *Models, Biological ; Risk Factors ; }, abstract = {BACKGROUND: Human Microbiome Project reveals the significant mutualistic influence between human body and microbes living in it. Such an influence lead to an interesting phenomenon that many noninfectious diseases are closely associated with diverse microbes. However, the identification of microbe-noninfectious disease associations (MDAs) is still a challenging task, because of both the high cost and the limitation of microbe cultivation. Thus, there is a need to develop fast approaches to screen potential MDAs. The growing number of validated MDAs enables us to meet the demand in a new insight. Computational approaches, especially machine learning, are promising to predict MDA candidates rapidly among a large number of microbe-disease pairs with the advantage of no limitation on microbe cultivation. Nevertheless, a few computational efforts at predicting MDAs are made so far.<br><br>RESULTS: In this paper, grouping a set of MDAs into a binary MDA matrix, we propose a novel predictive approach (BMCMDA) based on Binary Matrix Completion to predict potential MDAs. The proposed BMCMDA assumes that the incomplete observed MDA matrix is the summation of a latent parameterizing matrix and a noising matrix. It also assumes that the independently occurring subscripts of observed entries in the MDA matrix follows a binomial model. Adopting a standard mean-zero Gaussian distribution for the nosing matrix, we model the relationship between the parameterizing matrix and the MDA matrix under the observed microbe-disease pairs as a probit regression. With the recovered parameterizing matrix, BMCMDA deduces how likely a microbe would be associated with a particular disease. In the experiment under leave-one-out cross-validation, it exhibits the inspiring performance (AUC&#x2009;=&#x2009;0.906, AUPR =0.526) and demonstrates its superiority by ~&#x2009;7% and ~&#x2009;5% improvements in terms of AUC and AUPR respectively in the comparison with the pioneering approach KATZHMDA.<br><br>CONCLUSIONS: Our BMCMDA provides an effective approach for predicting MDAs and can be also extended to other similar predicting tasks of binary relationship (e.g. protein-protein interaction, drug-target interaction).}, }
@article {pmid30349509, year = {2018}, author = {Chaudhari, NM and Gautam, A and Gupta, VK and Kaur, G and Dutta, C and Paul, S}, title = {PanGFR-HM: A Dynamic Web Resource for Pan-Genomic and Functional Profiling of Human Microbiome With Comparative Features.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {2322}, pmid = {30349509}, issn = {1664-302X}, abstract = {The conglomerate of microorganisms inhabiting various body-sites of human, known as the human microbiome, is one of the key determinants of human health and disease. Comprehensive pan-genomic and functional analysis approach for human microbiome components can enrich our understanding about impact of microbiome on human health. By utilizing this approach we developed PanGFR-HM (http://www.bioinfo.iicb.res.in/pangfr-hm/) - a novel dynamic web-resource that integrates genomic and functional characteristics of 1293 complete microbial genomes available from Human Microbiome Project. The resource allows users to explore genomic/functional diversity and genome-based phylogenetic relationships between human associated microbial genomes, not provided by any other resource. The key features implemented here include pan-genome and functional analysis of organisms based on taxonomy or body-site, and comparative analysis between groups of organisms. The first feature can also identify probable gene-loss events and significantly over/under represented KEGG/COG categories within pan-genome. The unique second feature can perform comparative genomic, functional and pathways analysis between 4 groups of microbes. The dynamic nature of this resource enables users to define parameters for orthologous clustering and to select any set of organisms for analysis. As an application for comparative feature of PanGFR-HM, we performed a comparative analysis with 67 Lactobacillus genomes isolated from human gut, oral cavity and urogenital tract, and therefore characterized the body-site specific genes, enzymes and pathways. Altogether, PanGFR-HM, being unique in its content and functionality, is expected to provide a platform for microbiome-based comparative functional and evolutionary genomics.}, }
@article {pmid30349024, year = {2018}, author = {Chen, Z and Yeoh, YK and Hui, M and Wong, PY and Chan, MCW and Ip, M and Yu, J and Burk, RD and Chan, FKL and Chan, PKS}, title = {Diversity of macaque microbiota compared to the human counterparts.}, journal = {Scientific reports}, volume = {8}, number = {1}, pages = {15573}, pmid = {30349024}, issn = {2045-2322}, mesh = {Anal Canal/*microbiology ; Animals ; Cluster Analysis ; DNA, Bacterial/chemistry/genetics ; DNA, Ribosomal/chemistry/genetics ; Female ; Healthy Volunteers ; Humans ; Macaca mulatta ; *Microbiota ; Mouth/*microbiology ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Vagina/*microbiology ; }, abstract = {Studies on the microbial communities in non-human primate hosts provide unique insights in both evolution and function of microbes related to human health and diseases. Using 16S rRNA gene amplicon profiling, we examined the oral, anal and vaginal microbiota in a group of non-captive rhesus macaques (N = 116) and compared the compositions with the healthy communities from Human Microbiome Project. The macaque microbiota was dominated by Bacteroidetes, Firmicutes and Proteobacteria; however, there were marked differences in phylotypes enriched across body sites indicative of strong niche specialization. Compared to human gut microbiota where Bacteroides predominately enriched, the surveyed macaque anal community exhibited increased abundance of Prevotella. In contrast to the conserved human vaginal microbiota extremely dominated by Lactobacillus, the macaque vaginal microbial composition was highly diverse while lactobacilli were rare. A constant decrease of the vaginal microbiota diversity was observed among macaque samples from juvenile, adult without tubectomy, and adult with tubectomy, with the most notable distinction being the enrichment of Halomonas in juvenile and Saccharofermentans in contracepted adults. Both macaque and human oral microbiota were colonized with three most common oral bacterial genera: Streptococcus, Haemophilus and Veillonella, and shared relatively conserved communities to each other. A number of bacteria related to human pathogens were consistently detected in macaques. The findings delineate the range of structure and diversity of microbial communities in a wild macaque population, and enable the application of macaque as an animal model for future characterization of microbes in transmission, genomics and function.}, }
@article {pmid30332487, year = {2018}, author = {Wyman, SK and Avila-Herrera, A and Nayfach, S and Pollard, KS}, title = {A most wanted list of conserved microbial protein families with no known domains.}, journal = {PloS one}, volume = {13}, number = {10}, pages = {e0205749}, pmid = {30332487}, issn = {1932-6203}, mesh = {Bacterial Proteins/*chemistry/genetics ; Computational Biology ; *Databases, Nucleic Acid ; Humans ; Metagenome/*genetics ; Metagenomics ; Microbiota/*genetics ; Phylogeny ; Protein Domains/*genetics ; Sequence Homology, Nucleic Acid ; }, abstract = {The number and proportion of genes with no known function are growing rapidly. To quantify this phenomenon and provide criteria for prioritizing genes for functional characterization, we developed a bioinformatics pipeline that identifies robustly defined protein families with no annotated domains, ranks these with respect to phylogenetic breadth, and identifies them in metagenomics data. We applied this approach to 271 965 protein families from the SFams database and discovered many with no functional annotation, including >118 000 families lacking any known protein domain. From these, we prioritized 6 668 conserved protein families with at least three sequences from organisms in at least two distinct classes. These Function Unknown Families (FUnkFams) are present in Tara Oceans Expedition and Human Microbiome Project metagenomes, with distributions associated with sampling environment. Our findings highlight the extent of functional novelty in sequence databases and establish an approach for creating a "most wanted" list of genes to prioritize for further characterization.}, }
@article {pmid30275573, year = {2018}, author = {Gonzalez, A and Navas-Molina, JA and Kosciolek, T and McDonald, D and Vázquez-Baeza, Y and Ackermann, G and DeReus, J and Janssen, S and Swafford, AD and Orchanian, SB and Sanders, JG and Shorenstein, J and Holste, H and Petrus, S and Robbins-Pianka, A and Brislawn, CJ and Wang, M and Rideout, JR and Bolyen, E and Dillon, M and Caporaso, JG and Dorrestein, PC and Knight, R}, title = {Qiita: rapid, web-enabled microbiome meta-analysis.}, journal = {Nature methods}, volume = {15}, number = {10}, pages = {796-798}, pmid = {30275573}, issn = {1548-7105}, support = {P01 DK078669/DK/NIDDK NIH HHS/United States ; R01 MD011389/MD/NIMHD NIH HHS/United States ; R01 HG004872/HG/NHGRI NIH HHS/United States ; R01 HL140976/HL/NHLBI NIH HHS/United States ; P30 MH062512/MH/NIMH NIH HHS/United States ; }, mesh = {Computational Biology/*methods ; Humans ; *Internet ; *Metagenomics ; *Microbiota ; *Software ; User-Computer Interface ; }, abstract = {Multi-omic insights into microbiome function and composition typically advance one study at a time. However, in order for relationships across studies to be fully understood, data must be aggregated into meta-analyses. This makes it possible to generate new hypotheses by finding features that are reproducible across biospecimens and data layers. Qiita dramatically accelerates such integration tasks in a web-based microbiome-comparison platform, which we demonstrate with Human Microbiome Project and Integrative Human Microbiome Project (iHMP) data.}, }
@article {pmid30269615, year = {2018}, author = {Aziz, RK and Hegazy, SM and Yasser, R and Rizkallah, MR and ElRakaiby, MT}, title = {Drug pharmacomicrobiomics and toxicomicrobiomics: from scattered reports to systematic studies of drug-microbiome interactions.}, journal = {Expert opinion on drug metabolism &amp; toxicology}, volume = {14}, number = {10}, pages = {1043-1055}, doi = {10.1080/17425255.2018.1530216}, pmid = {30269615}, issn = {1744-7607}, mesh = {Animals ; Drug-Related Side Effects and Adverse Reactions/*epidemiology ; Gastrointestinal Microbiome ; Humans ; *Microbiota ; Pharmaceutical Preparations/administration &amp; dosage/*metabolism ; Pharmacogenetics/methods ; Precision Medicine/methods ; Toxicogenetics/methods ; }, abstract = {Pharmacomicrobiomics and toxicomicrobiomics study how variations within the human microbiome (the combination of human-associated microbial communities and their genomes) affect drug disposition, action, and toxicity. These emerging fields, interconnecting microbiology, bioinformatics, systems pharmacology, and toxicology, complement pharmacogenomics and toxicogenomics, expanding the scope of precision medicine. Areas covered: This article reviews some of the most recently reported pharmacomicrobiomic and toxicomicrobiomic interactions. Examples include the impact of the human gut microbiota on cardiovascular drugs, natural products, and chemotherapeutic agents, including immune checkpoint inhibitors. Although the gut microbiota has been the most extensively studied, some key drug-microbiome interactions involve vaginal, intratumoral, and environmental bacteria, and are briefly discussed here. Additionally, computational resources, moving the field from cataloging to predicting interactions, are introduced. Expert opinion: The rapid pace of discovery triggered by the Human Microbiome Project is moving pharmacomicrobiomic research from scattered observations to systematic studies focusing on screening microbiome variants against different drug classes. Better representation of all human populations will improve such studies by avoiding sampling bias, and the integration of multiomic studies with designed experiments will allow establishing causation. In the near future, pharmacomicrobiomic testing is expected to be a key step in screening novel drugs and designing precision therapeutics.}, }
@article {pmid30249275, year = {2018}, author = {He, Y and Wu, W and Wu, S and Zheng, HM and Li, P and Sheng, HF and Chen, MX and Chen, ZH and Ji, GY and Zheng, ZD and Mujagond, P and Chen, XJ and Rong, ZH and Chen, P and Lyu, LY and Wang, X and Xu, JB and Wu, CB and Yu, N and Xu, YJ and Yin, J and Raes, J and Ma, WJ and Zhou, HW}, title = {Linking gut microbiota, metabolic syndrome and economic status based on a population-level analysis.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {172}, pmid = {30249275}, issn = {2049-2618}, mesh = {Adult ; Aged ; Bacteria/classification/genetics/*isolation &amp; purification ; Economic Status ; Feces/microbiology ; Female ; *Gastrointestinal Microbiome ; Humans ; Male ; Metabolic Syndrome/*economics/metabolism/*microbiology ; Middle Aged ; Phylogeny ; }, abstract = {BACKGROUND: The metabolic syndrome (MetS) epidemic is associated with economic development, lifestyle transition and dysbiosis of gut microbiota, but these associations are rarely studied at the population scale. Here, we utilised the Guangdong Gut Microbiome Project (GGMP), the largest Eastern population-based gut microbiome dataset covering individuals with different economic statuses, to investigate the relationships between the gut microbiome and host physiology, diet, geography, physical activity and socioeconomic status.<br><br>RESULTS: At the population level, 529 OTUs were significantly associated with MetS. OTUs from Proteobacteria and Firmicutes (other than Ruminococcaceae) were mainly positively associated with MetS, whereas those from Bacteroidetes and Ruminococcaceae were negatively associated with MetS. Two hundred fourteen OTUs were significantly associated with host economic status (140 positive and 74 negative associations), and 157 of these OTUs were also MetS associated. A microbial MetS index was formulated to represent the overall gut dysbiosis of MetS. The values of this index were significantly higher in MetS subjects regardless of their economic status or geographical location. The index values did not increase with increasing personal economic status, although the prevalence of MetS was significantly higher in people of higher economic status. With increased economic status, the study population tended to consume more fruits and vegetables and fewer grains, whereas meat consumption was unchanged. Sedentary time was significantly and positively associated with higher economic status. The MetS index showed an additive effect with sedentary lifestyle, as the prevalence of MetS in individuals with high MetS index values and unhealthy lifestyles was significantly higher than that in the rest of the population.<br><br>CONCLUSIONS: The gut microbiome is associated with MetS and economic status. A prolonged sedentary lifestyle, rather than Westernised dietary patterns, was the most notable lifestyle change in our Eastern population along with economic development. Moreover, gut dysbiosis and a Western lifestyle had an additive effect on increasing MetS prevalence.}, }
@article {pmid30230652, year = {2018}, author = {Little, MS and Ervin, SM and Walton, WG and Tripathy, A and Xu, Y and Liu, J and Redinbo, MR}, title = {Active site flexibility revealed in crystal structures of Parabacteroides merdae β-glucuronidase from the human gut microbiome.}, journal = {Protein science : a publication of the Protein Society}, volume = {27}, number = {12}, pages = {2010-2022}, pmid = {30230652}, issn = {1469-896X}, support = {P30 ES010126/ES/NIEHS NIH HHS/United States ; R01 CA207416/CA/NCI NIH HHS/United States ; }, mesh = {Bacteroidaceae/*enzymology ; Catalytic Domain ; Crystallography, X-Ray ; *Gastrointestinal Microbiome ; Glucuronidase/*metabolism ; Humans ; Models, Molecular ; Protein Conformation ; }, abstract = {β-Glucuronidase (GUS) enzymes in the gastrointestinal tract are involved in maintaining mammalian-microbial symbiosis and can play key roles in drug efficacy and toxicity. Parabacteroides merdae GUS was identified as an abundant mini-Loop 2 (mL2) type GUS enzyme in the Human Microbiome Project gut metagenomic database. Here, we report the crystal structure of P. merdae GUS and highlight the differences between this enzyme and extant structures of gut microbial GUS proteins. We find that P. merdae GUS exhibits a distinct tetrameric quaternary structure and that the mL2 motif traces a unique path within the active site, which also includes two arginines distinctive to this GUS. We observe two states of the P. merdae GUS active site; a loop repositions itself by more than 50 Å to place a functionally-relevant residue into the enzyme's catalytic site. Finally, we find that P. merdae GUS is able to bind to homo and heteropolymers of the polysaccharide alginic acid. Together, these data broaden our understanding of the structural and functional diversity in the GUS family of enzymes present in the human gut microbiome and point to specialization as an important feature of microbial GUS orthologs.}, }
@article {pmid30197908, year = {2017}, author = {Xia, Y and Sun, J}, title = {Hypothesis Testing and Statistical Analysis of Microbiome.}, journal = {Genes &amp; diseases}, volume = {4}, number = {3}, pages = {138-148}, pmid = {30197908}, issn = {2352-4820}, support = {R01 DK105118/DK/NIDDK NIH HHS/United States ; R01 DK114126/DK/NIDDK NIH HHS/United States ; }, abstract = {After the initiation of Human Microbiome Project in 2008, various biostatistic and bioinformatic tools for data analysis and computational methods have been developed and applied to microbiome studies. In this review and perspective, we discuss the research and statistical hypotheses in gut microbiome studies, focusing on mechanistic concepts that underlie the complex relationships among host, microbiome, and environment. We review the current available statistic tools and highlight recent progress of newly developed statistical methods and models. Given the current challenges and limitations in biostatistic approaches and tools, we discuss the future direction in developing statistical methods and models for the microbiome studies.}, }
@article {pmid30172254, year = {2018}, author = {Lager, S and de Goffau, MC and Sovio, U and Peacock, SJ and Parkhill, J and Charnock-Jones, DS and Smith, GCS}, title = {Detecting eukaryotic microbiota with single-cell sensitivity in human tissue.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {151}, pmid = {30172254}, issn = {2049-2618}, support = {MR/K021133/1/MRC_/Medical Research Council/United Kingdom ; G1100221//Medical Research Council/United Kingdom ; //Department of Health/United Kingdom ; }, mesh = {Adult ; Eukaryota/classification/genetics/*isolation &amp; purification ; Female ; Humans ; Placenta/*microbiology/*parasitology ; Plasmodium falciparum/genetics/isolation &amp; purification ; Pregnancy ; Pregnancy Complications/*microbiology/*parasitology/physiopathology ; Pregnancy Outcome ; Saccharomyces cerevisiae/genetics/isolation &amp; purification ; Toxoplasma/genetics/isolation &amp; purification ; Young Adult ; }, abstract = {BACKGROUND: Fetal growth restriction, pre-eclampsia, and pre-term birth are major adverse pregnancy outcomes. These complications are considerable contributors to fetal/maternal morbidity and mortality worldwide. A significant proportion of these cases are thought to be due to dysfunction of the placenta. However, the underlying mechanisms of placental dysfunction are unclear. The aim of the present study was to investigate whether adverse pregnancy outcomes are associated with evidence of placental eukaryotic infection.<br><br>RESULTS: We modified the 18S Illumina Amplicon Protocol of the Earth Microbiome Project and made it capable of detecting just a single spiked-in genome copy of Plasmodium falciparum, Saccharomyces cerevisiae, or Toxoplasma gondii among more than 70,000 human cells. Using this method, we were unable to detect eukaryotic pathogens in placental biopsies in instances of adverse pregnancy outcome (n&#x2009;=&#x2009;199) or in healthy controls (n&#x2009;=&#x2009;99).<br><br>CONCLUSIONS: Eukaryotic infection of the placenta is not an underlying cause of the aforementioned pregnancy complications. Possible clinical applications for this non-targeted, yet extremely sensitive, eukaryotic screening method are manifest.}, }
@article {pmid30155556, year = {2019}, author = {Ma, ZS}, title = {Sketching the Human Microbiome Biogeography with DAR (Diversity-Area Relationship) Profiles.}, journal = {Microbial ecology}, volume = {77}, number = {3}, pages = {821-838}, pmid = {30155556}, issn = {1432-184X}, mesh = {Bacteria/classification/genetics/*isolation &amp; purification ; *Biodiversity ; Humans ; Metagenomics ; *Microbiota ; Models, Biological ; }, abstract = {SAR (species area relationship) is a classic ecological theory that has been extensively investigated and applied in the studies of global biogeography and biodiversity conservation in macro-ecology. It has also found important applications in microbial ecology in recent years thanks to the breakthroughs in metagenomic sequencing technology. Nevertheless, SAR has a serious limitation for practical applications-ignoring the species abundance and treating all species as equally abundant. This study aims to explore the biogeography discoveries of human microbiome over 18 sites of 5 major microbiome habitats, establish the baseline DAR (diversity-area scaling relationship) parameters, and perform comparisons with the classic SAR. The extension from SAR to DAR by adopting the Hill numbers as diversity measures not only overcomes the previously mentioned flaw of SAR but also allows for obtaining a series of important findings on the human microbiome biodiversity and biogeography. Specifically, two types of DAR models were built, the traditional power law (PL) and power law with exponential cutoff (PLEC), using comprehensive datasets from the HMP (human microbiome project). Furthermore, the biogeography "maps" for 18 human microbiome sites using their DAR profiles for assessing and predicting the diversity scaling across individuals, PDO profiles (pair-wise diversity overlap) for measuring diversity overlap (similarity), and MAD profile (for predicting the maximal accrual diversity in a population) were sketched out. The baseline biogeography maps for the healthy human microbiome diversity can offer guidelines for conserving human microbiome diversity and investigating the health implications of the human microbiome diversity and heterogeneity.}, }
@article {pmid30131772, year = {2018}, author = {Ma, ZS and Li, L and Li, W}, title = {Assessing and Interpreting the Within-Body Biogeography of Human Microbiome Diversity.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {1619}, pmid = {30131772}, issn = {1664-302X}, abstract = {A human body hosts a relatively independent microbiome including five major regional biomes (i.e., airway, oral, gut, skin, and urogenital). Each of them may possess different regional characteristics with important implications to our health and diseases (i.e., so-termed microbiome associated diseases). Nevertheless, these regional microbiomes are connected with each other through diffusions and migrations. Here, we investigate the within-body (intra-individual) distribution feature of microbiome diversity via diversity area relationship (DAR) modeling, which, to the best of our knowledge, has not been systematically studied previously. We utilized the Hill numbers for measuring alpha and beta-diversities and built 1,200 within-body DAR models with to date the most comprehensive human microbiome datasets of 18 sites from the human microbiome project (HMP) cohort. We established the intra-DAR profile (z-q pattern: the diversity scaling parameter z of the power law (PL) at diversity order q = 0-3), intra-PDO (pair-wise diversity overlap) profile (g-q), and intra-MAD (maximal accrual diversity) profile (D max-q) for the within-body biogeography of the human microbiome. These profiles constitute the "maps" of the within-body biogeography, and offer important insights on the within-body distribution of the human microbiome. Furthermore, we investigated the heterogeneity among individuals in their biogeography parameters and found that there is not an "average Joe" that can represent majority of individuals in a cohort or population. For example, we found that most individuals in the HMP cohort have relatively lower maximal accrual diversity (MAD) or in the "long tail" of the so-termed power law distribution. In the meantime, there are a small number of individuals in the cohort who possess disproportionally higher MAD values. These findings may have important implications for personalized medicine of the human microbiome associated diseases in practice, besides their theoretical significance in microbiome research such as establishing the baseline for the conservation of human microbiome.}, }
@article {pmid30129002, year = {2018}, author = {Lin, J and Kimura, BY and Oikarinen, S and Nykter, M}, title = {Bioinformatics Assembling and Assessment of Novel Coxsackievirus B1 Genome.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {1838}, number = {}, pages = {261-272}, doi = {10.1007/978-1-4939-8682-8_18}, pmid = {30129002}, issn = {1940-6029}, mesh = {*Computational Biology/methods ; Enterovirus B, Human/*genetics ; *Genome, Viral ; *Genomics/methods ; Humans ; Metagenome ; Metagenomics/methods/standards ; Quality Control ; }, abstract = {The human microbiome project via application of metagenomic next-generation sequencing techniques has found surprising large and diverse amounts of microbial sequences across different body sites. There is a wave of investigators studying autoimmune related diseases designing from birth case and control studies to elucidate microbial associations and potential direct triggers. Sequencing analysis, considered big data as it typically includes millions of reads, is challenging but particularly demanding and complex is virome profiling due to its lack of pan-viral genomic signature. Impressively thousands of virus complete genomes have been deposited and these high-quality references are core components of virus profiling pipelines and databases. Still it is commonly known that most viral sequences do not map to known viruses. Moreover human viruses, particularly RNA groups, are notoriously heterogeneous due to high mutation rates. Here, we present the related assembling challenges and a series of bioinformatics steps that were applied in the construction of the complete consensus genome of a novel clinical isolate of Coxsackievirus B1. We further demonstrate our effort in calling mutations between prototype Coxsackievirus B1 sequence from GenBank and serial clinical isolate genome grown in cell culture.}, }
@article {pmid30098679, year = {2018}, author = {Kroon, SJ and Ravel, J and Huston, WM}, title = {Cervicovaginal microbiota, women's health, and reproductive outcomes.}, journal = {Fertility and sterility}, volume = {110}, number = {3}, pages = {327-336}, doi = {10.1016/j.fertnstert.2018.06.036}, pmid = {30098679}, issn = {1556-5653}, support = {R01 NR014826/NR/NINR NIH HHS/United States ; R01 NR014784/NR/NINR NIH HHS/United States ; R01 AI116799/AI/NIAID NIH HHS/United States ; }, mesh = {Cervix Uteri/microbiology/*physiology ; Dysbiosis/complications/diagnosis/microbiology ; Female ; Humans ; Infertility, Female/diagnosis/etiology/microbiology ; Lactobacillus/isolation &amp; purification/physiology ; Microbiota/*physiology ; Pregnancy ; Reproduction/*physiology ; Vagina/microbiology/*physiology ; *Women's Health/trends ; }, abstract = {The human microbiome project has shown a remarkable diversity of microbial ecology within the human body. The vaginal microbiota is unique in that in many women it is most often dominated by Lactobacillus species. However, in some women it lacks Lactobacillus spp. and is comprised of a wide array of strict and facultative anaerobes, a state that broadly correlates with increased risk for infection, disease, and poor reproductive and obstetric outcomes. Interestingly, the level of protection against infection can also vary by species and strains of Lactobacillus, and some species although dominant are not always optimal. This factors into the risk of contracting sexually transmitted infections and possibly influences the occurrence of resultant adverse reproductive outcomes such as tubal factor infertility. The composition and function of the vaginal microbiota appear to play an important role in pregnancy and fertility treatment outcomes and future research in this field will shed further translational mechanistic understanding onto the interplay of the vaginal microbiota with women's health and reproduction.}, }
@article {pmid30071492, year = {2018}, author = {Hanssen, EN and Liland, KH and Gill, P and Snipen, L}, title = {Optimizing body fluid recognition from microbial taxonomic profiles.}, journal = {Forensic science international. Genetics}, volume = {37}, number = {}, pages = {13-20}, doi = {10.1016/j.fsigen.2018.07.012}, pmid = {30071492}, issn = {1878-0326}, mesh = {Bacteria/*genetics ; Discriminant Analysis ; Feces/*microbiology ; Female ; Forensic Genetics/methods ; High-Throughput Nucleotide Sequencing ; Humans ; Least-Squares Analysis ; Microbiota ; Mouth/*microbiology ; Nasal Cavity/*microbiology ; *RNA, Ribosomal, 16S ; Sensitivity and Specificity ; Sequence Analysis, DNA ; Skin/*microbiology ; Vagina/*microbiology ; }, abstract = {In forensics the DNA-profile is used to identify the person who left a biological trace, but information on body fluid can also be essential in the evidence evaluation process. Microbial composition data could potentially be used for body fluid recognition as an improved alternative to the currently used presumptive tests. We have developed a customized workflow for interpretation of bacterial 16S sequence data based on a model composed of Partial Least Squares (PLS) in combination with Linear Discriminant Analysis (LDA). Large data sets from the Human Microbiome Project (HMP) and the American Gut Project (AGP) were used to test different settings in order to optimize performance. From the initial cross-validation of body fluid recognition within the HMP data, the optimal overall accuracy was close to 98%. Sensitivity values for the fecal and oral samples were ≥0.99, followed by the vaginal samples with 0.98 and the skin and nasal samples with 0.96 and 0.81 respectively. Specificity values were high for all 5 categories, mostly >0.99. This optimal performance was achieved by using the following settings: Taxonomic profiles based on operational taxonomic units (OTUs) with 0.98 identity (OTU98), Aitchisons simplex transform with C = 1 pseudo-count and no regularization (r = 1) in the PLS step. Variable selection did not improve the performance further. To test for robustness across sequencing platforms, we also trained the classifier on HMP data and tested on the AGP data set. In this case, the standard OTU based approach showed moderately decline in accuracy. However, by using taxonomic profiles made by direct assignment of reads to a genus, we were able to nearly maintain the high accuracy levels. The optimal combination of settings was still used, except the taxonomic level being genus instead of OTU98. The performance may be improved even further by using higher resolution taxonomic bins.}, }
@article {pmid30059804, year = {2018}, author = {Tripathi, A and Marotz, C and Gonzalez, A and Vázquez-Baeza, Y and Song, SJ and Bouslimani, A and McDonald, D and Zhu, Q and Sanders, JG and Smarr, L and Dorrestein, PC and Knight, R}, title = {Are microbiome studies ready for hypothesis-driven research?.}, journal = {Current opinion in microbiology}, volume = {44}, number = {}, pages = {61-69}, pmid = {30059804}, issn = {1879-0364}, support = {R01 HG004872/HG/NHGRI NIH HHS/United States ; R01 HL140976/HL/NHLBI NIH HHS/United States ; R01 MD011389/MD/NIMHD NIH HHS/United States ; }, mesh = {Animals ; Biomedical Research/methods/*standards ; Humans ; *Microbiota ; }, abstract = {Hypothesis-driven research has led to many scientific advances, but hypotheses cannot be tested in isolation: rather, they require a framework of aggregated scientific knowledge to allow questions to be posed meaningfully. This framework is largely still lacking in microbiome studies, and the only way to create it is by discovery-driven, tool-driven, and standards-driven research projects. Here we illustrate these issues using several such non-hypothesis-driven projects from our own laboratories, including spatial mapping, the American Gut Project, the Earth Microbiome Project (which is an umbrella project integrating many smaller hypothesis-driven projects), and the knowledgebase-driven tools GNPS and Qiita. We argue that an investment of community resources in infrastructure tasks, and in the controls and standards that underpin them, will greatly enhance the investment in hypothesis-driven research programs.}, }
@article {pmid30057577, year = {2018}, author = {Riiser, ES and Haverkamp, THA and Borgan, &#xd8; and Jakobsen, KS and Jentoft, S and Star, B}, title = {A Single Vibrionales 16S rRNA Oligotype Dominates the Intestinal Microbiome in Two Geographically Separated Atlantic cod Populations.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {1561}, pmid = {30057577}, issn = {1664-302X}, abstract = {Atlantic cod (Gadus morhua) provides an interesting species for the study of host-microbe interactions because it lacks the MHC II complex that is involved in the presentation of extracellular pathogens. Nonetheless, little is known about the diversity of its microbiome in natural populations. Here, we use high-throughput sequencing of the 16S rRNA V4 region, amplified with the primer design of the Earth Microbiome Project (EMP), to investigate the microbial composition in gut content and mucosa of 22 adult individuals from two coastal populations in Norway, located 470 km apart. We identify a core microbiome of 23 OTUs (97% sequence similarity) in all individuals that comprises 93% of the total number of reads. The most abundant orders are classified as Vibrionales, Fusobacteriales, Clostridiales, and Bacteroidales. While mucosal samples show significantly lower diversity than gut content samples, no differences in OTU community composition are observed between the two geographically separated populations. All specimens share a limited number of abundant OTUs. Moreover, the most abundant OTU consists of a single oligotype (order Vibrionales, genus Photobacterium) that represents nearly 50% of the reads in both locations. Our results suggest that these microbiomes comprise a limited number of species or that the EMP V4 primers do not yield sufficient resolution to confidently separate these communities. Our study contributes to a growing body of literature that shows limited spatial differentiation of the intestinal microbiomes in marine fish based on 16S rRNA sequencing, highlighting the need for multi-gene approaches to provide more insight into the diversity of these communities.}, }
@article {pmid30042392, year = {2018}, author = {Clayton, JB and Al-Ghalith, GA and Long, HT and Tuan, BV and Cabana, F and Huang, H and Vangay, P and Ward, T and Minh, VV and Tam, NA and Dat, NT and Travis, DA and Murtaugh, MP and Covert, H and Glander, KE and Nadler, T and Toddes, B and Sha, JCM and Singer, R and Knights, D and Johnson, TJ}, title = {Associations Between Nutrition, Gut Microbiome, and Health in A Novel Nonhuman Primate Model.}, journal = {Scientific reports}, volume = {8}, number = {1}, pages = {11159}, pmid = {30042392}, issn = {2045-2322}, support = {T32 DA007097/DA/NIDA NIH HHS/United States ; }, mesh = {Animals ; Bacteroidetes/classification/genetics ; Biodiversity ; Cercopithecidae/*physiology ; Chloroplasts/genetics ; Diet, Vegan ; Dysbiosis ; Endangered Species ; Feces/microbiology ; Firmicutes/classification/genetics ; Gastrointestinal Microbiome/*genetics ; Gastrointestinal Tract/microbiology ; *Health Status ; Life Style ; Metagenome ; Models, Animal ; Nutritional Status/*physiology ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, RNA ; Statistics, Nonparametric ; }, abstract = {Red-shanked doucs (Pygathrix nemaeus) are endangered, foregut-fermenting colobine primates which are difficult to maintain in captivity. There are critical gaps in our understanding of their natural lifestyle, including dietary habits such as consumption of leaves, unripe fruit, flowers, seeds, and other plant parts. There is also a lack of understanding of enteric adaptations, including their unique microflora. To address these knowledge gaps, we used the douc as a model to study relationships between gastrointestinal microbial community structure and lifestyle. We analyzed published fecal samples as well as detailed dietary history from doucs with four distinct lifestyles (wild, semi-wild, semi-captive, and captive) and determined gastrointestinal bacterial microbiome composition using 16S rRNA sequencing. A clear gradient of microbiome composition was revealed along an axis of natural lifestyle disruption, including significant associations with diet, biodiversity, and microbial function. We also identified potential microbial biomarkers of douc dysbiosis, including Bacteroides and Prevotella, which may be related to health. Our results suggest a gradient-like shift in captivity causes an attendant shift to severe gut dysbiosis, thereby resulting in gastrointestinal issues.}, }
@article {pmid30010718, year = {2019}, author = {Zheng, W and Mao, Q and Genco, RJ and Wactawski-Wende, J and Buck, M and Cai, Y and Sun, Y}, title = {A parallel computational framework for ultra-large-scale sequence clustering analysis.}, journal = {Bioinformatics (Oxford, England)}, volume = {35}, number = {3}, pages = {380-388}, pmid = {30010718}, issn = {1367-4811}, support = {R01 DE024523/DE/NIDCR NIH HHS/United States ; R01 AI125982/AI/NIAID NIH HHS/United States ; }, mesh = {*Algorithms ; *Cluster Analysis ; Computational Biology ; *Microbiota ; *Software ; }, abstract = {MOTIVATION: The rapid development of sequencing technology has led to an explosive accumulation of genomic data. Clustering is often the first step to be performed in sequence analysis. However, existing methods scale poorly with respect to the unprecedented growth of input data size. As high-performance computing systems are becoming widely accessible, it is highly desired that a clustering method can easily scale to handle large-scale sequence datasets by leveraging the power of parallel computing.<br><br>RESULTS: In this paper, we introduce SLAD (Separation via Landmark-based Active Divisive clustering), a generic computational framework that can be used to parallelize various de novo operational taxonomic unit (OTU) picking methods and comes with theoretical guarantees on both accuracy and efficiency. The proposed framework was implemented on Apache Spark, which allows for easy and efficient utilization of parallel computing resources. Experiments performed on various datasets demonstrated that SLAD can significantly speed up a number of popular de novo OTU picking methods and meanwhile maintains the same level of accuracy. In particular, the experiment on the Earth Microbiome Project dataset (&#x223c;2.2B reads, 437 GB) demonstrated the excellent scalability of the proposed method.<br><br>Open-source software for the proposed method is freely available at https://www.acsu.buffalo.edu/~yijunsun/lab/SLAD.html.<br><br>SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.}, }
@article {pmid30006754, year = {2018}, author = {Sorbellini, E and Rucco, M and Rinaldi, F}, title = {Photodynamic and photobiological effects of light-emitting diode (LED) therapy in dermatological disease: an update.}, journal = {Lasers in medical science}, volume = {33}, number = {7}, pages = {1431-1439}, pmid = {30006754}, issn = {1435-604X}, mesh = {Aging/radiation effects ; Alopecia/drug therapy/radiotherapy ; Humans ; *Light ; *Photochemotherapy ; Photosensitizing Agents/therapeutic use ; Skin Diseases/*drug therapy ; }, abstract = {Benefit deriving from the use of light is known since ancient time, but, only in the last decades of twentieth century, we witnessed the rapid expansion of knowledge and techniques. Light-emitted diode (LED)-based devices represent the emerging and safest tool for the treatment of many conditions such as skin inflammatory conditions, aging, and disorders linked to hair growth. The present work reviews the current knowledge about LED-based therapeutic approaches in different skin and hair disorders. LED therapy represents the emerging and safest tool for the treatment of many conditions such as skin inflammatory conditions, aging, and disorders linked to hair growth. The use of LED in the treatment of such conditions has now entered common practice among dermatologists. Additional controlled studies are still needed to corroborate the efficacy of such kind of treatment.}, }
@article {pmid29984938, year = {2018}, author = {Li, BL and Cheng, L and Zhou, XD and Peng, X}, title = {[Research progress on the relationship between oral microbes and digestive system diseases].}, journal = {Hua xi kou qiang yi xue za zhi = Huaxi kouqiang yixue zazhi = West China journal of stomatology}, volume = {36}, number = {3}, pages = {331-335}, pmid = {29984938}, issn = {2618-0456}, mesh = {*Dental Caries/microbiology ; *Digestive System Diseases/microbiology ; Humans ; *Microbiota ; *Mouth Diseases/microbiology ; *Periodontal Diseases ; }, abstract = {The human microbiome project promoted further understanding on human oral microbes. Besides oral diseases such as dental caries, periodontal disease, and oral cancer, oral microbes are closely associated with systematic diseases. They have a close connection with digestive system diseases and even contribute to the origination and progression of colorectal cancer. By reviewing recent studies involving oral microbe-related digestive systemic diseases, we aim to propose the considerable role of oral microbes in relation to digestive systemic diseases and the way of oral microbes to multiple organs of digestive system.}, }
@article {pmid29974051, year = {2018}, author = {Fankhauser, M and Moser, C and Nyfeler, T}, title = {Patents as Early Indicators of Technology and Investment Trends: Analyzing the Microbiome Space as a Case Study.}, journal = {Frontiers in bioengineering and biotechnology}, volume = {6}, number = {}, pages = {84}, pmid = {29974051}, issn = {2296-4185}, abstract = {The human microbiome is the collective of microbes living in symbiosis on and within humans. Modulating its composition and function has become an attractive means for the prevention and treatment of a variety of diseases including cancer. Since the initiation of the human microbiome project in 2007, the number of academic publications and active patent families around the microbiome has grown exponentially. Screening patent databases can be useful for the early detection and the tracking of new technology trends. However, it is not sufficient to assess portfolio sizes because emerging players with small but high-quality patent portfolios will be missed within the noise of large but low-quality portfolio owners. Here we used the consolidated database and software tool PatentSight to benchmark patent portfolios, and to analyze key patent owners and innovators in the microbiome space. Our study shows how in-depth patent analyses combining qualitative and quantitative parameters can identify actionable early indicators of technology and investment trends from large patent datasets.}, }
@article {pmid29900563, year = {2018}, author = {Coleman, M and Elkins, C and Gutting, B and Mongodin, E and Solano-Aguilar, G and Walls, I}, title = {Microbiota and Dose Response: Evolving Paradigm of Health Triangle.}, journal = {Risk analysis : an official publication of the Society for Risk Analysis}, volume = {38}, number = {10}, pages = {2013-2028}, doi = {10.1111/risa.13121}, pmid = {29900563}, issn = {1539-6924}, mesh = {Animals ; *Bacteria ; *Dysbiosis ; *Gastrointestinal Microbiome ; Genomics ; Humans ; Immunity, Innate ; Immunity, Mucosal ; Intestines/immunology/microbiology ; Mice ; Models, Biological ; Prebiotics ; Probiotics/*analysis ; Risk Assessment/*methods ; }, abstract = {SRA Dose-Response and Microbial Risk Analysis Specialty Groups jointly sponsored symposia that addressed the intersections between the "microbiome revolution" and dose response. Invited speakers presented on innovations and advances in gut and nasal microbiota (normal microbial communities) in the first decade after the Human Microbiome Project began. The microbiota and their metabolites are now known to influence health and disease directly and indirectly, through modulation of innate and adaptive immune systems and barrier function. Disruption of healthy microbiota is often associated with changes in abundance and diversity of core microbial species (dysbiosis), caused by stressors including antibiotics, chemotherapy, and disease. Nucleic-acid-based metagenomic methods demonstrated that the dysbiotic host microbiota no longer provide normal colonization resistance to pathogens, a critical component of innate immunity of the superorganism. Diverse pathogens, probiotics, and prebiotics were considered in human and animal models (in vivo and in vitro). Discussion included approaches for design of future microbial dose-response studies to account for the presence of the indigenous microbiota that provide normal colonization resistance, and the absence of the protective microbiota in dysbiosis. As NextGen risk analysis methodology advances with the "microbiome revolution," a proposed new framework, the Health Triangle, may replace the old paradigm based on the Disease Triangle (focused on host, pathogen, and environment) and germophobia. Collaborative experimental designs are needed for testing hypotheses about causality in dose-response relationships for pathogens present in our environments that clearly compete in complex ecosystems with thousands of bacterial species dominating the healthy superorganism.}, }
@article {pmid29878050, year = {2018}, author = {Albayrak, L and Khanipov, K and Golovko, G and Fofanov, Y}, title = {Detection of multi-dimensional co-exclusion patterns in microbial communities.}, journal = {Bioinformatics (Oxford, England)}, volume = {34}, number = {21}, pages = {3695-3701}, doi = {10.1093/bioinformatics/bty414}, pmid = {29878050}, issn = {1367-4811}, mesh = {Humans ; *Microbiota ; Software ; }, abstract = {MOTIVATION: Identification of complex relationships among members of microbial communities is key to understand and control the microbiota. Co-exclusion is arguably one of the most important patterns reflecting micro-organisms' intolerance to each other's presence. Knowing these relations opens an opportunity to manipulate microbiotas, personalize anti-microbial and probiotic treatments as well as guide microbiota transplantation. The co-exclusion pattern however, cannot be appropriately described by a linear function nor its strength be estimated using covariance or (negative) Pearson and Spearman correlation coefficients. This manuscript proposes a way to quantify the strength and evaluate the statistical significance of co-exclusion patterns between two, three or more variables describing a microbiota and allows one to extend analysis beyond micro-organism abundance by including other microbiome associated measurements such as, pH, temperature etc., as well as estimate the expected numbers of false positive co-exclusion patterns in a co-exclusion network.<br><br>RESULTS: The implemented computational pipeline (CoEx) tested against 2380 microbial profiles (samples) from The Human Microbiome Project resulted in body-site specific pairwise co-exclusion patterns.<br><br>C++&#x2009;source code for calculation of the score and P-value for two, three and four dimensional co-exclusion patterns as well as source code and executable files for the CoEx pipeline are available at https://scsb.utmb.edu/labgroups/fofanov/co-exclusion_in_microbial_communities.asp.<br><br>SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.}, }
@article {pmid29862519, year = {2018}, author = {Clayton, JB and Gomez, A and Amato, K and Knights, D and Travis, DA and Blekhman, R and Knight, R and Leigh, S and Stumpf, R and Wolf, T and Glander, KE and Cabana, F and Johnson, TJ}, title = {The gut microbiome of nonhuman primates: Lessons in ecology and evolution.}, journal = {American journal of primatology}, volume = {80}, number = {6}, pages = {e22867}, doi = {10.1002/ajp.22867}, pmid = {29862519}, issn = {1098-2345}, mesh = {Animals ; Bacteria/classification ; *Biological Evolution ; Diet/veterinary ; Ecology ; *Gastrointestinal Microbiome ; Phylogeny ; Primates/classification/immunology/*microbiology/physiology ; }, abstract = {The mammalian gastrointestinal (GI) tract is home to trillions of bacteria that play a substantial role in host metabolism and immunity. While progress has been made in understanding the role that microbial communities play in human health and disease, much less attention has been given to host-associated microbiomes in nonhuman primates (NHPs). Here we review past and current research exploring the gut microbiome of NHPs. First, we summarize methods for characterization of the NHP gut microbiome. Then we discuss variation in gut microbiome composition and function across different NHP taxa. Finally, we highlight how studying the gut microbiome offers new insights into primate nutrition, physiology, and immune system function, as well as enhances our understanding of primate ecology and evolution. Microbiome approaches are useful tools for studying relevant issues in primate ecology. Further study of the gut microbiome of NHPs will offer new insight into primate ecology and evolution as well as human health.}, }
@article {pmid29854953, year = {2018}, author = {Cardona, C and Lax, S and Larsen, P and Stephens, B and Hampton-Marcell, J and Edwardson, CF and Henry, C and Van Bonn, B and Gilbert, JA}, title = {Environmental Sources of Bacteria Differentially Influence Host-Associated Microbial Dynamics.}, journal = {mSystems}, volume = {3}, number = {3}, pages = {}, pmid = {29854953}, issn = {2379-5077}, support = {P30 DK042086/DK/NIDDK NIH HHS/United States ; T32 EB009412/EB/NIBIB NIH HHS/United States ; }, abstract = {Host-associated microbial dynamics are influenced by dietary and immune factors, but how exogenous microbial exposure shapes host-microbe dynamics remains poorly characterized. To investigate this phenomenon, we characterized the skin, rectum, and respiratory tract-associated microbiota in four aquarium-housed dolphins daily over a period of 6 weeks, including administration of a probiotic during weeks 4 to 6. The environmental bacterial sources were also characterized, including the animals' human handlers, the aquarium air and water, and the dolphins' food supply. Continuous microbial exposure occurred between all sites, yet each environment maintained a characteristic microbiota, suggesting that the majority of exposure events do not result in colonization. Small changes in water physicochemistry had a significant but weak correlation with change in dolphin-associated bacterial richness but had no influence on phylogenetic diversity. Food and air microbiota were the richest and had the largest conditional influence on other microbiota in the absence of probiotics, but during probiotic administration, food alone had the largest influence on the stability of the dolphin microbiota. Our results suggest that respiratory tract and gastrointestinal epithelium interactions with air- and food-associated microbes had the biggest influence on host-microbiota dynamics, while other interactions, such as skin transmission, played only a minor role. Finally, direct oral stimulation with a foreign exogenous microbial source can have a profound effect on microbial stability. IMPORTANCE These results provide valuable insights into the ecological influence of exogenous microbial exposure, as well as laying the foundation for improving aquarium management practices. By comparing data for dolphins from aquaria that use natural versus artificial seawater, we demonstrate the potential influence of aquarium water disinfection procedures on dolphin microbial dynamics.}, }
@article {pmid29795809, year = {2018}, author = {McDonald, D and Hyde, E and Debelius, JW and Morton, JT and Gonzalez, A and Ackermann, G and Aksenov, AA and Behsaz, B and Brennan, C and Chen, Y and DeRight Goldasich, L and Dorrestein, PC and Dunn, RR and Fahimipour, AK and Gaffney, J and Gilbert, JA and Gogul, G and Green, JL and Hugenholtz, P and Humphrey, G and Huttenhower, C and Jackson, MA and Janssen, S and Jeste, DV and Jiang, L and Kelley, ST and Knights, D and Kosciolek, T and Ladau, J and Leach, J and Marotz, C and Meleshko, D and Melnik, AV and Metcalf, JL and Mohimani, H and Montassier, E and Navas-Molina, J and Nguyen, TT and Peddada, S and Pevzner, P and Pollard, KS and Rahnavard, G and Robbins-Pianka, A and Sangwan, N and Shorenstein, J and Smarr, L and Song, SJ and Spector, T and Swafford, AD and Thackray, VG and Thompson, LR and Tripathi, A and Vázquez-Baeza, Y and Vrbanac, A and Wischmeyer, P and Wolfe, E and Zhu, Q and ,  and Knight, R}, title = {American Gut: an Open Platform for Citizen Science Microbiome Research.}, journal = {mSystems}, volume = {3}, number = {3}, pages = {}, pmid = {29795809}, issn = {2379-5077}, support = {MR/N01183X/1/MRC_/Medical Research Council/United Kingdom ; P30 DK042086/DK/NIDDK NIH HHS/United States ; P30 DK043351/DK/NIDDK NIH HHS/United States ; MR/N030125/1/MRC_/Medical Research Council/United Kingdom ; T32 GM007752/GM/NIGMS NIH HHS/United States ; /WT_/Wellcome Trust/United Kingdom ; }, abstract = {Although much work has linked the human microbiome to specific phenotypes and lifestyle variables, data from different projects have been challenging to integrate and the extent of microbial and molecular diversity in human stool remains unknown. Using standardized protocols from the Earth Microbiome Project and sample contributions from over 10,000 citizen-scientists, together with an open research network, we compare human microbiome specimens primarily from the United States, United Kingdom, and Australia to one another and to environmental samples. Our results show an unexpected range of beta-diversity in human stool microbiomes compared to environmental samples; demonstrate the utility of procedures for removing the effects of overgrowth during room-temperature shipping for revealing phenotype correlations; uncover new molecules and kinds of molecular communities in the human stool metabolome; and examine emergent associations among the microbiome, metabolome, and the diversity of plants that are consumed (rather than relying on reductive categorical variables such as veganism, which have little or no explanatory power). We also demonstrate the utility of the living data resource and cross-cohort comparison to confirm existing associations between the microbiome and psychiatric illness and to reveal the extent of microbiome change within one individual during surgery, providing a paradigm for open microbiome research and education. IMPORTANCE We show that a citizen science, self-selected cohort shipping samples through the mail at room temperature recaptures many known microbiome results from clinically collected cohorts and reveals new ones. Of particular interest is integrating n = 1 study data with the population data, showing that the extent of microbiome change after events such as surgery can exceed differences between distinct environmental biomes, and the effect of diverse plants in the diet, which we confirm with untargeted metabolomics on hundreds of samples.}, }
@article {pmid29760467, year = {2018}, author = {Xian, P and Xuedong, Z and Xin, X and Yuqing, L and Yan, L and Jiyao, L and Xiaoquan, S and Shi, H and Jian, X and Ga, L}, title = {The Oral Microbiome Bank of China.}, journal = {International journal of oral science}, volume = {10}, number = {2}, pages = {16}, pmid = {29760467}, issn = {2049-3169}, mesh = {China ; Humans ; *Microbiota ; Mouth/*microbiology ; }, abstract = {The human microbiome project (HMP) promoted further understanding of human oral microbes. However, research on the human oral microbiota has not made as much progress as research on the gut microbiota. Currently, the causal relationship between the oral microbiota and oral diseases remains unclear, and little is known about the link between the oral microbiota and human systemic diseases. To further understand the contribution of the oral microbiota in oral diseases and systemic diseases, a Human Oral Microbiome Database (HOMD) was established in the US. The HOMD includes 619 taxa in 13 phyla, and most of the microorganisms are from American populations. Due to individual differences in the microbiome, the HOMD does not reflect the Chinese oral microbial status. Herein, we established a new oral microbiome database-the Oral Microbiome Bank of China (OMBC, http://www.sklod.org/ombc). Currently, the OMBC includes information on 289 bacterial strains and 720 clinical samples from the Chinese population, along with lab and clinical information. The OMBC is the first curated description of a Chinese-associated microbiome; it provides tools for use in investigating the role of the oral microbiome in health and diseases, and will give the community abundant data and strain information for future oral microbial studies.}, }
@article {pmid29724017, year = {2018}, author = {Avershina, E and Angell, IL and Simpson, M and Storrø, O and Øien, T and Johnsen, R and Rudi, K}, title = {Low Maternal Microbiota Sharing across Gut, Breast Milk and Vagina, as Revealed by 16S rRNA Gene and Reduced Metagenomic Sequencing.}, journal = {Genes}, volume = {9}, number = {5}, pages = {}, pmid = {29724017}, issn = {2073-4425}, abstract = {The maternal microbiota plays an important role in infant gut colonization. In this work we have investigated which bacterial species are shared across the breast milk, vaginal and stool microbiotas of 109 women shortly before and after giving birth using 16S rRNA gene sequencing and a novel reduced metagenomic sequencing (RMS) approach in a subgroup of 16 women. All the species predicted by the 16S rRNA gene sequencing were also detected by RMS analysis and there was good correspondence between their relative abundances estimated by both approaches. Both approaches also demonstrate a low level of maternal microbiota sharing across the population and RMS analysis identified only two species common to most women and in all sample types (Bifidobacterium longum and Enterococcus faecalis). Breast milk was the only sample type that had significantly higher intra- than inter- individual similarity towards both vaginal and stool samples. We also searched our RMS dataset against an in silico generated reference database derived from bacterial isolates in the Human Microbiome Project. The use of this reference-based search enabled further separation of Bifidobacterium longum into Bifidobacterium longum ssp. longum and Bifidobacterium longum ssp. infantis. We also detected the Lactobacillus rhamnosus GG strain, which was used as a probiotic supplement by some women, demonstrating the potential of RMS approach for deeper taxonomic delineation and estimation.}, }
@article {pmid29721973, year = {2018}, author = {Rowan, S and Taylor, A}, title = {The Role of Microbiota in Retinal Disease.}, journal = {Advances in experimental medicine and biology}, volume = {1074}, number = {}, pages = {429-435}, doi = {10.1007/978-3-319-75402-4_53}, pmid = {29721973}, issn = {0065-2598}, mesh = {Animals ; Conjunctiva/microbiology ; Cornea/microbiology ; Diabetic Retinopathy/microbiology/prevention &amp; control ; Disease Models, Animal ; Gastrointestinal Microbiome/drug effects/physiology ; Germ-Free Life ; Glaucoma/microbiology ; Humans ; Macular Degeneration/microbiology ; Metformin/pharmacology ; Mice ; Microbiota/*physiology ; Mouth/microbiology ; Retinal Diseases/*microbiology ; Uveitis/microbiology ; }, abstract = {The ten years since the first publications on the human microbiome project have brought enormous attention and insight into the role of the human microbiome in health and disease. Connections between populations of microbiota and ocular disease are now being established, and increased accessibility to microbiome research and insights into other diseases is expected to yield enormous information in the coming years. With the characterization of the ocular microbiome, important insights have already been made regarding corneal and conjunctival tissues. Roles for non-ocular microbiomes in complex retinal diseases are now being evaluated. For example, the gut microbiome has been implicated in the pathogenesis of uveitis. This short review will summarize the few studies linking gut or oral microbiota to diabetic retinopathy (DR), glaucoma, and age-related macular degeneration (AMD). We will also conjecture where the most significant findings still remain to be elucidated. Finally, we will propose the gut-retina axis, related but distinct from the gut-brain axis.}, }
@article {pmid29692798, year = {2018}, author = {Roche-Lima, A and Carrasquillo-Carrión, K and Gómez-Moreno, R and Cruz, JM and Velázquez-Morales, DM and Rogozin, IB and Baerga-Ortiz, A}, title = {The Presence of Genotoxic and/or Pro-inflammatory Bacterial Genes in Gut Metagenomic Databases and Their Possible Link With Inflammatory Bowel Diseases.}, journal = {Frontiers in genetics}, volume = {9}, number = {}, pages = {116}, pmid = {29692798}, issn = {1664-8021}, support = {U54 MD007600/MD/NIMHD NIH HHS/United States ; R25 GM061838/GM/NIGMS NIH HHS/United States ; G12 RR003051/RR/NCRR NIH HHS/United States ; G12 MD007600/MD/NIMHD NIH HHS/United States ; R21 CA198963/CA/NCI NIH HHS/United States ; }, abstract = {Background: The human gut microbiota is a dynamic community of microorganisms that mediate important biochemical processes. Differences in the gut microbial composition have been associated with inflammatory bowel diseases (IBD) and other intestinal disorders. In this study, we quantified and compared the frequencies of eight genotoxic and/or pro-inflammatory bacterial genes found in metagenomic Whole Genome Sequences (mWGSs) of samples from individuals with IBD vs. a cohort of healthy human subjects. Methods: The eight selected gene sequences were clbN, clbB, cif, cnf-1, usp, tcpC from Escherichia coli, gelE from Enterococcus faecalis and murB from Akkermansia muciniphila. We also included the sequences for the conserved murB genes from E. coli and E. faecalis as markers for the presence of Enterobacteriaceae or Enterococci in the samples. The gene sequences were chosen based on their previously reported ability to disrupt normal cellular processes to either promote inflammation or to cause DNA damage in cultured cells or animal models, which could be linked to a role in IBD. The selected sequences were searched in three different mWGS datasets accessed through the Human Microbiome Project (HMP): a healthy cohort (N = 251), a Crohn's disease cohort (N = 60) and an ulcerative colitis cohort (N = 17). Results: Firstly, the sequences for the murB housekeeping genes from Enterobacteriaceae and Enterococci were more frequently found in the IBD cohorts (32% E. coli in IBD vs. 12% in healthy; 13% E. faecalis in IBD vs. 3% in healthy) than in the healthy cohort, confirming earlier reports of a higher presence of both of these taxa in IBD. For some of the sequences in our study, especially usp and gelE, their frequency was even more sharply increased in the IBD cohorts than in the healthy cohort, suggesting an association with IBD that is not easily explained by the increased presence of E. coli or E. faecalis in those samples. Conclusion: Our results suggest a significant association between the presence of some of these genotoxic or pro-inflammatory gene sequences and IBDs. In addition, these results illustrate the power and limitations of the HMP database in the detection of possible clinical correlations for individual bacterial genes.}, }
@article {pmid29668831, year = {2018}, author = {Maziarz, M and Pfeiffer, RM and Wan, Y and Gail, MH}, title = {Using standard microbiome reference groups to simplify beta-diversity analyses and facilitate independent validation.}, journal = {Bioinformatics (Oxford, England)}, volume = {34}, number = {19}, pages = {3249-3257}, pmid = {29668831}, issn = {1367-4811}, mesh = {*Computational Biology ; Feces/microbiology ; Humans ; *Microbiota ; Nose/microbiology ; }, abstract = {MOTIVATION: Comparisons of microbiome communities across populations are often based on pairwise distance measures (beta-diversity). Standard analyses (principal coordinate plots, permutation tests, kernel methods) require access to primary data if another investigator wants to add or compare independent data. We propose using standard reference measurements to simplify microbiome beta-diversity analyses, to make them more transparent, and to facilitate independent validation and comparisons across studies.<br><br>RESULTS: Using stool and nasal reference sets from the Human Microbiome Project (HMP), we computed mean distances (actually Bray-Curtis or Pearson correlation dissimilarities) to each reference set for each new sample. Thus, each new sample has two mean distances that can be plotted and analyzed with classical statistical methods. To test the approach, we studied independent (not reference) HMP subjects. Simple Hotelling tests demonstrated statistically significant differences in mean distances to reference sets between all pairs of body sites (stool, skin, nasal, saliva and vagina) at the phylum, class, order, family and genus levels. Using the distance to a single reference set was usually sufficient, but using both reference sets always worked well. The use of reference sets simplifies standard analyses of beta-diversity and facilitates the independent validation and combining of such data because others can compute distances to the same reference sets. Moreover, standard statistical methods for survival analysis, logistic regression and other procedures can be applied to vectors of mean distances to reference sets, thereby greatly expanding the potential uses of beta-diversity information. More work is needed to identify the best reference sets for particular applications.<br><br>https://github.com/NCI-biostats/microbiome-fixed-reference.<br><br>SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.}, }
@article {pmid29658784, year = {2018}, author = {Popic, V and Kuleshov, V and Snyder, M and Batzoglou, S}, title = {Fast Metagenomic Binning via Hashing and Bayesian Clustering.}, journal = {Journal of computational biology : a journal of computational molecular cell biology}, volume = {25}, number = {7}, pages = {677-688}, doi = {10.1089/cmb.2017.0250}, pmid = {29658784}, issn = {1557-8666}, mesh = {*Bayes Theorem ; Cluster Analysis ; Computational Biology/*statistics &amp; numerical data ; Humans ; Metagenome/genetics ; Metagenomics/*statistics &amp; numerical data ; Microbiota/*genetics ; }, abstract = {We introduce GATTACA, a framework for fast unsupervised binning of metagenomic contigs. Similar to recent approaches, GATTACA clusters contigs based on their coverage profiles across a large cohort of metagenomic samples; however, unlike previous methods that rely on read mapping, GATTACA quickly estimates these profiles from kmer counts stored in a compact index. This approach can result in over an order of magnitude speedup, while matching the accuracy of earlier methods on synthetic and real data benchmarks. It also provides a way to index metagenomic samples (e.g., from public repositories such as the Human Microbiome Project) offline once and reuse them across experiments; furthermore, the small size of the sample indices allows them to be easily transferred and stored. Leveraging the MinHash technique, GATTACA also provides an efficient way to identify publicly available metagenomic data that can be incorporated into the set of reference metagenomes to further improve binning accuracy. Thus, enabling easy indexing and reuse of publicly available metagenomic data sets, GATTACA makes accurate metagenomic analyses accessible to a much wider range of researchers.}, }
@article {pmid29657969, year = {2018}, author = {Gilbert, JA and Jansson, JK and Knight, R}, title = {Earth Microbiome Project and Global Systems Biology.}, journal = {mSystems}, volume = {3}, number = {3}, pages = {}, pmid = {29657969}, issn = {2379-5077}, support = {P30 DK042086/DK/NIDDK NIH HHS/United States ; }, }
@article {pmid29608646, year = {2018}, author = {Sinha, R and Goedert, JJ and Vogtmann, E and Hua, X and Porras, C and Hayes, R and Safaeian, M and Yu, G and Sampson, J and Ahn, J and Shi, J}, title = {Quantification of Human Microbiome Stability Over 6 Months: Implications for Epidemiologic Studies.}, journal = {American journal of epidemiology}, volume = {187}, number = {6}, pages = {1282-1290}, pmid = {29608646}, issn = {1476-6256}, support = {R01 CA164964/CA/NCI NIH HHS/United States ; R03 CA159414/CA/NCI NIH HHS/United States ; }, mesh = {Feces/microbiology ; Female ; *Gastrointestinal Microbiome ; Humans ; Male ; Time Factors ; }, abstract = {Temporal variation in microbiome measurements can reduce statistical power in research studies. Quantification of this variation is essential for designing studies of chronic disease. We analyzed 16S ribosomal RNA profiles in paired biological specimens separated by 6 months from 3 studies conducted during 1985-2013 (a National Cancer Institute colorectal cancer study, a Costa Rica study, and the Human Microbiome Project). We evaluated temporal stability by calculating intraclass correlation coefficients (ICCs). Sample sizes needed in order to detect microbiome differences between equal numbers of cases and controls for a nested case-control design were calculated on the basis of estimated ICCs. Across body sites, 12 phylum-level ICCs were greater than 0.5. Similarly, 11 alpha-diversity ICCs were greater than 0.5. Fecal beta-diversity estimates had ICCs over 0.5. For a single collection with most microbiome metrics, detecting an odds ratio of 2.0 would require 300-500 cases when matching 1 case to 1 control at P = 0.05. Use of 2 or 3 sequential specimens reduces the number of required subjects by 40%-50% for low-ICC metrics. Relative abundances of major phyla and alpha-diversity metrics have low temporal stability. Thus, detecting associations of moderate effect size with these metrics will require large sample sizes. Because beta diversity for feces is reasonably stable over time, smaller sample sizes can detect associations with community composition. Sequential prediagnostic specimens from thousands of prospectively ascertained cases are required to detect modest disease associations with particular microbiome metrics.}, }
@article {pmid29568289, year = {2018}, author = {Flores Saiffe Farías, A and Mendizabal, AP and Morales, JA}, title = {An Ontology Systems Approach on Human Brain Expression and Metaproteomics.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {406}, pmid = {29568289}, issn = {1664-302X}, abstract = {Research in the last decade has shown growing evidence of the gut microbiota influence on brain physiology. While many mechanisms of this influence have been proposed in animal models, most studies in humans are the result of a pathology-dysbiosis association and very few have related the presence of certain taxa with brain substructures or molecular pathways. In this paper, we associated the functional ontologies in the differential expression of brain substructures from the Allen Brain Atlas database, with those of the metaproteome from the Human Microbiome Project. Our results showed several coherent clustered ontologies where many taxa could influence brain expression and physiology. A detailed analysis of psychobiotics showed specific slim ontologies functionally associated with substructures in the basal ganglia and cerebellar cortex. Some of the most relevant slim ontology groups are related to Ion transport, Membrane potential, Synapse, DNA and RNA metabolism, and Antigen processing, while the most relevant neuropathology found was Parkinson disease. In some of these cases, new hypothetical gut microbiota-brain interaction pathways are proposed.}, }
@article {pmid29492330, year = {2017}, author = {Lang, JM and Coil, DA and Neches, RY and Brown, WE and Cavalier, D and Severance, M and Hampton-Marcell, JT and Gilbert, JA and Eisen, JA}, title = {A microbial survey of the International Space Station (ISS).}, journal = {PeerJ}, volume = {5}, number = {}, pages = {e4029}, pmid = {29492330}, issn = {2167-8359}, abstract = {BACKGROUND: Modern advances in sequencing technology have enabled the census of microbial members of many natural ecosystems. Recently, attention is increasingly being paid to the microbial residents of human-made, built ecosystems, both private (homes) and public (subways, office buildings, and hospitals). Here, we report results of the characterization of the microbial ecology of a singular built environment, the International Space Station (ISS). This ISS sampling involved the collection and microbial analysis (via 16S rDNA PCR) of 15 surfaces sampled by swabs onboard the ISS. This sampling was a component of Project MERCCURI (Microbial Ecology Research Combining Citizen and University Researchers on ISS). Learning more about the microbial inhabitants of the "buildings" in which we travel through space will take on increasing importance, as plans for human exploration continue, with the possibility of colonization of other planets and moons.<br><br>RESULTS: Sterile swabs were used to sample 15 surfaces onboard the ISS. The sites sampled were designed to be analogous to samples collected for (1) the Wildlife of Our Homes project and (2) a study of cell phones and shoes that were concurrently being collected for another component of Project MERCCURI. Sequencing of the 16S rDNA genes amplified from DNA extracted from each swab was used to produce a census of the microbes present on each surface sampled. We compared the microbes found on the ISS swabs to those from both homes on Earth and data from the Human Microbiome Project.<br><br>CONCLUSIONS: While significantly different from homes on Earth and the Human Microbiome Project samples analyzed here, the microbial community composition on the ISS was more similar to home surfaces than to the human microbiome samples. The ISS surfaces are species-rich with 1,036-4,294 operational taxonomic units (OTUs per sample). There was no discernible biogeography of microbes on the 15 ISS surfaces, although this may be a reflection of the small sample size we were able to obtain.}, }
@article {pmid29490879, year = {2019}, author = {Wu, WK and Chen, CC and Panyod, S and Chen, RA and Wu, MS and Sheen, LY and Chang, SC}, title = {Optimization of fecal sample processing for microbiome study - The journey from bathroom to bench.}, journal = {Journal of the Formosan Medical Association = Taiwan yi zhi}, volume = {118}, number = {2}, pages = {545-555}, doi = {10.1016/j.jfma.2018.02.005}, pmid = {29490879}, issn = {0929-6646}, mesh = {DNA/*isolation &amp; purification ; Feces/*microbiology ; *Gastrointestinal Microbiome ; Humans ; Metagenomics ; Reagent Kits, Diagnostic ; Sequence Analysis, DNA ; Specimen Handling/*methods/*standards ; }, abstract = {Although great interest has been displayed by researchers in the contribution of gut microbiota to human health, there is still no standard protocol with consensus to guarantee the sample quality of metagenomic analysis. Here we reviewed existing methodology studies and present suggestions for optimizing research pipeline from fecal sample collection to DNA extraction. First, we discuss strategies of clinical metadata collection as common confounders for microbiome research. Second, we propose general principles for freshly collected fecal sample and its storage and share a DIY stool collection kit protocol based on the manual procedure of Human Microbiome Project (HMP). Third, we provide a useful information of collection kit with DNA stabilization buffers and compare their pros and cons for multi-omic study. Fourth, we offer technical strategies as well as information of novel tools for sample aliquoting before long-term storage. Fifth, we discuss the substantial impact of different DNA extraction protocols on technical variations of metagenomic analysis. And lastly, we point out the limitation of current methods and the unmet needs for better quality control of metagenomic analysis. We hope the information provided here will help investigators in this exciting field to advance their studies while avoiding experimental artifacts.}, }
@article {pmid29378630, year = {2018}, author = {Kolde, R and Franzosa, EA and Rahnavard, G and Hall, AB and Vlamakis, H and Stevens, C and Daly, MJ and Xavier, RJ and Huttenhower, C}, title = {Host genetic variation and its microbiome interactions within the Human Microbiome Project.}, journal = {Genome medicine}, volume = {10}, number = {1}, pages = {6}, pmid = {29378630}, issn = {1756-994X}, support = {U54 DK102557/DK/NIDDK NIH HHS/United States ; U54 HG003067/HG/NHGRI NIH HHS/United States ; P30 DK043351/DK/NIDDK NIH HHS/United States ; 5U54HG003067-13/HG/NHGRI NIH HHS/United States ; U54 DE023798/DE/NIDCR NIH HHS/United States ; }, mesh = {*Genetic Variation ; Genotype ; Humans ; Metagenome ; Microbiota/*genetics ; Principal Component Analysis ; Sequence Analysis, DNA ; Tissue Donors ; }, abstract = {BACKGROUND: Despite the increasing recognition that microbial communities within the human body are linked to health, we have an incomplete understanding of the environmental and molecular interactions that shape the composition of these communities. Although host genetic factors play a role in these interactions, these factors have remained relatively unexplored given the requirement for large population-based cohorts in which both genotyping and microbiome characterization have been performed.<br><br>METHODS: We performed whole-genome sequencing of 298 donors from the Human Microbiome Project (HMP) healthy cohort study to accompany existing deep characterization of their microbiomes at various body sites. This analysis yielded an average sequencing depth of 32x, with which we identified 27 million (M) single nucleotide variants and 2.3&#xa0;M insertions-deletions.<br><br>RESULTS: Taxonomic composition and functional potential of the microbiome covaried significantly with genetic principal components in the gastrointestinal tract and oral communities, but not in the nares or vaginal microbiota. Example associations included validation of known associations between FUT2 secretor status, as well as a variant conferring hypolactasia near the LCT gene, with Bifidobacterium longum abundance in stool. The associations of microbial features with both high-level genetic attributes and single variants were specific to particular body sites, highlighting the opportunity to find unique genetic mechanisms controlling microbiome properties in the microbial communities from multiple body sites.<br><br>CONCLUSIONS: This study adds deep sequencing of host genomes to the body-wide microbiome sequences already extant from the HMP healthy cohort, creating a unique, versatile, and well-controlled reference for future studies seeking to identify host genetic modulators of the microbiome.}, }
@article {pmid29373999, year = {2018}, author = {Fuks, G and Elgart, M and Amir, A and Zeisel, A and Turnbaugh, PJ and Soen, Y and Shental, N}, title = {Combining 16S rRNA gene variable regions enables high-resolution microbial community profiling.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {17}, pmid = {29373999}, issn = {2049-2618}, support = {R01 HL122593/HL/NHLBI NIH HHS/United States ; 3-11174//Ministry of Science and Technology, Israel/International ; }, mesh = {Algorithms ; Animals ; Bacteria/classification ; Computer Simulation ; DNA Probes/genetics ; DNA, Bacterial/genetics ; Drosophila melanogaster/*microbiology ; Microbiota ; Phylogeny ; Polymerase Chain Reaction/*methods ; RNA, Ribosomal, 16S/*genetics ; Sequence Analysis, DNA/*methods ; }, abstract = {BACKGROUND: Most of our knowledge about the remarkable microbial diversity on Earth comes from sequencing the 16S rRNA gene. The use of next-generation sequencing methods has increased sample number and sequencing depth, but the read length of the most widely used sequencing platforms today is quite short, requiring the researcher to choose a subset of the gene to sequence (typically 16-33% of the total length). Thus, many bacteria may share the same amplified region, and the resolution of profiling is inherently limited. Platforms that offer ultra-long read lengths, whole genome shotgun sequencing approaches, and computational frameworks formerly suggested by us and by others all allow different ways to circumvent this problem yet suffer various shortcomings. There is a need for a simple and low-cost 16S rRNA gene-based profiling approach that harnesses the short read length to provide a much larger coverage of the gene to allow for high resolution, even in harsh conditions of low bacterial biomass and fragmented DNA.<br><br>RESULTS: This manuscript suggests Short MUltiple Regions Framework (SMURF), a method to combine sequencing results from different PCR-amplified regions to provide one coherent profiling. The de facto amplicon length is the total length of all amplified regions, thus providing much higher resolution compared to current techniques. Computationally, the method solves a convex optimization problem that allows extremely fast reconstruction and requires only moderate memory. We demonstrate the increase in resolution by in silico simulations and by profiling two mock mixtures and real-world biological samples. Reanalyzing a mock mixture from the Human Microbiome Project achieved about twofold improvement in resolution when combing two independent regions. Using a custom set of six primer pairs spanning about 1200&#xa0;bp (80%) of the 16S rRNA gene, we were able to achieve ~&#x2009;100-fold improvement in resolution compared to a single region, over a mock mixture of common human gut bacterial isolates. Finally, the profiling of a Drosophila melanogaster microbiome using the set of six primer pairs provided a ~&#x2009;100-fold increase in resolution and thus enabling efficient downstream analysis.<br><br>CONCLUSIONS: SMURF enables the identification of near full-length 16S rRNA gene sequences in microbial communities, having resolution superior compared to current techniques. It may be applied to standard sample preparation protocols with very little modifications. SMURF also paves the way to high-resolution profiling of low-biomass and fragmented DNA, e.g., in the case of formalin-fixed and paraffin-embedded samples, fossil-derived DNA, or DNA exposed to other degrading conditions. The approach is not restricted to combining amplicons of the 16S rRNA gene and may be applied to any set of amplicons, e.g., in multilocus sequence typing (MLST).}, }
@article {pmid29340028, year = {2017}, author = {Guerrero-Preston, R and White, JR and Godoy-Vitorino, F and Rodríguez-Hilario, A and Navarro, K and González, H and Michailidi, C and Jedlicka, A and Canapp, S and Bondy, J and Dziedzic, A and Mora-Lagos, B and Rivera-Alvarez, G and Ili-Gangas, C and Brebi-Mieville, P and Westra, W and Koch, W and Kang, H and Marchionni, L and Kim, Y and Sidransky, D}, title = {High-resolution microbiome profiling uncovers Fusobacterium nucleatum, Lactobacillus gasseri/johnsonii, and Lactobacillus vaginalis associated to oral and oropharyngeal cancer in saliva from HPV positive and HPV negative patients treated with surgery and chemo-radiation.}, journal = {Oncotarget}, volume = {8}, number = {67}, pages = {110931-110948}, pmid = {29340028}, issn = {1949-2553}, support = {RC2 DE020957/DE/NIDCR NIH HHS/United States ; P50 DE019032/DE/NIDCR NIH HHS/United States ; R01 CA121113/CA/NCI NIH HHS/United States ; K01 CA164092/CA/NCI NIH HHS/United States ; U01 CA084986/CA/NCI NIH HHS/United States ; P20 GM103475/GM/NIGMS NIH HHS/United States ; }, abstract = {Microbiome studies show altered microbiota in head and neck squamous cell carcinoma (HNSCC), both in terms of taxonomic composition and metabolic capacity. These studies utilized a traditional bioinformatics methodology, which allows for accurate taxonomic assignment down to the genus level, but cannot accurately resolve species level membership. We applied Resphera Insight, a high-resolution methodology for 16S rRNA taxonomic assignment that is able to provide species-level context in its assignments of 16S rRNA next generation sequencing (NGS) data. Resphera Insight applied to saliva samples from HNSCC patients and healthy controls led to the discovery that a subset of HNSCC saliva samples is significantly enriched with commensal species from the vaginal flora, including Lactobacillus gasseri/johnsonii (710x higher in saliva) and Lactobacillus vaginalis (52x higher in saliva). These species were not observed in normal saliva from Johns Hopkins patients, nor in 16S rRNA NGS saliva samples from the Human Microbiome Project (HMP). Interestingly, both species were only observed in saliva from Human Papilloma Virus (HPV) positive and HPV negative oropharyngeal cancer patients. We confirmed the representation of both species in HMP data obtained from mid-vagina (n=128) and vaginal introitus (n=121) samples. Resphera Insight also led to the discovery that Fusobacterium nucleatum, an oral cavity flora commensal bacterium linked to colon cancer, is enriched (600x higher) in saliva from a subset of HNSCC patients with advanced tumors stages. Together, these high-resolution analyses on 583 samples suggest a possible role for bacterial species in the therapeutic outcome of HPV positive and HPV negative HNSCC patients.}, }
@article {pmid29311644, year = {2018}, author = {Schirmer, M and Franzosa, EA and Lloyd-Price, J and McIver, LJ and Schwager, R and Poon, TW and Ananthakrishnan, AN and Andrews, E and Barron, G and Lake, K and Prasad, M and Sauk, J and Stevens, B and Wilson, RG and Braun, J and Denson, LA and Kugathasan, S and McGovern, DPB and Vlamakis, H and Xavier, RJ and Huttenhower, C}, title = {Dynamics of metatranscription in the inflammatory bowel disease gut microbiome.}, journal = {Nature microbiology}, volume = {3}, number = {3}, pages = {337-346}, pmid = {29311644}, issn = {2058-5276}, support = {U54 DK102557/DK/NIDDK NIH HHS/United States ; U01 DK062413/DK/NIDDK NIH HHS/United States ; P30 DK043351/DK/NIDDK NIH HHS/United States ; P01 DK046763/DK/NIDDK NIH HHS/United States ; UL1 TR001881/TR/NCATS NIH HHS/United States ; P30 DK078392/DK/NIDDK NIH HHS/United States ; R01 DK092405/DK/NIDDK NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Child ; Colitis, Ulcerative/microbiology ; Crohn Disease/microbiology ; Dysbiosis ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*genetics ; Gene Expression Profiling ; Humans ; Inflammatory Bowel Diseases/*microbiology ; Longitudinal Studies ; Male ; *Metagenomics ; Phenotype ; *Transcription, Genetic ; Young Adult ; }, abstract = {Inflammatory bowel disease (IBD) is a group of chronic diseases of the digestive tract that affects millions of people worldwide. Genetic, environmental and microbial factors have been implicated in the onset and exacerbation of IBD. However, the mechanisms associating gut microbial dysbioses and aberrant immune responses remain largely unknown. The integrative Human Microbiome Project seeks to close these gaps by examining the dynamics of microbiome functionality in disease by profiling the gut microbiomes of >100 individuals sampled over a 1-year period. Here, we present the first results based on 78 paired faecal metagenomes and metatranscriptomes, and 222 additional metagenomes from 59 patients with Crohn's disease, 34 with ulcerative colitis and 24 non-IBD control patients. We demonstrate several cases in which measures of microbial gene expression in the inflamed gut can be informative relative to metagenomic profiles of functional potential. First, although many microbial organisms exhibited concordant DNA and RNA abundances, we also detected species-specific biases in transcriptional activity, revealing predominant transcription of pathways by individual microorganisms per host (for example, by Faecalibacterium prausnitzii). Thus, a loss of these organisms in disease may have more far-reaching consequences than suggested by their genomic abundances. Furthermore, we identified organisms that were metagenomically abundant but inactive or dormant in the gut with little or no expression (for example, Dialister invisus). Last, certain disease-specific microbial characteristics were more pronounced or only detectable at the transcript level, such as pathways that were predominantly expressed by different organisms in patients with IBD (for example, Bacteroides vulgatus and Alistipes putredinis). This provides potential insights into gut microbial pathway transcription that can vary over time, inducing phenotypical changes that are complementary to those linked to metagenomic abundances. The study's results highlight the strength of analysing both the activity and the presence of gut microorganisms to provide insight into the role of the microbiome in IBD.}, }
@article {pmid29281638, year = {2017}, author = {Lo, C and Marculescu, R}, title = {MPLasso: Inferring microbial association networks using prior microbial knowledge.}, journal = {PLoS computational biology}, volume = {13}, number = {12}, pages = {e1005915}, pmid = {29281638}, issn = {1553-7358}, mesh = {Algorithms ; Computational Biology ; Data Mining ; Databases, Genetic ; Humans ; Machine Learning ; Microbial Consortia/genetics/*physiology ; Microbial Interactions/*physiology ; Microbiota/genetics/*physiology ; Models, Biological ; }, abstract = {Due to the recent advances in high-throughput sequencing technologies, it becomes possible to directly analyze microbial communities in human body and environment. To understand how microbial communities adapt, develop, and interact with the human body and the surrounding environment, one of the fundamental challenges is to infer the interactions among different microbes. However, due to the compositional and high-dimensional nature of microbial data, statistical inference cannot offer reliable results. Consequently, new approaches that can accurately and robustly estimate the associations (putative interactions) among microbes are needed to analyze such compositional and high-dimensional data. We propose a novel framework called Microbial Prior Lasso (MPLasso) which integrates graph learning algorithm with microbial co-occurrences and associations obtained from scientific literature by using automated text mining. We show that MPLasso outperforms existing models in terms of accuracy, microbial network recovery rate, and reproducibility. Furthermore, the association networks we obtain from the Human Microbiome Project datasets show credible results when compared against laboratory data.}, }
@article {pmid29277868, year = {2018}, author = {Maltez Thomas, A and Prata Lima, F and Maria Silva Moura, L and Maria da Silva, A and Dias-Neto, E and Setubal, JC}, title = {Comparative Metagenomics.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {1704}, number = {}, pages = {243-260}, doi = {10.1007/978-1-4939-7463-4_8}, pmid = {29277868}, issn = {1940-6029}, mesh = {Computational Biology ; Humans ; Metagenomics/*methods ; *Microbiota ; Mouth Mucosa/*microbiology ; Sequence Analysis, DNA/methods ; Software ; Tongue/*microbiology ; }, abstract = {Thanks in large part to newer, better, and cheaper DNA sequencing technologies, an enormous number of metagenomic sequence datasets have been and continue to be generated, covering a huge variety of environmental niches, including several different human body sites. Comparing these metagenomes and identifying their commonalities and differences is a challenging task, due not only to the large amounts of data, but also because there are several methodological considerations that need to be taken into account to ensure an appropriate and sound comparison between datasets. In this chapter, we describe current techniques aimed at comparing metagenomes generated by 16S ribosomal RNA and shotgun DNA sequencing, emphasizing methodological issues that arise in these comparative studies. We provide a detailed case study to illustrate some of these techniques using data from the Human Microbiome Project comparing the microbial communities from ten buccal mucosa samples with ten tongue dorsum samples in terms of alpha diversity, beta diversity, and their taxonomic and functional profiles.}, }
@article {pmid29253074, year = {2018}, author = {Huang, L and Krüger, J and Sczyrba, A}, title = {Analyzing large scale genomic data on the cloud with Sparkhit.}, journal = {Bioinformatics (Oxford, England)}, volume = {34}, number = {9}, pages = {1457-1465}, pmid = {29253074}, issn = {1367-4811}, mesh = {Algorithms ; High-Throughput Nucleotide Sequencing/*methods ; Humans ; Metagenomics/*methods ; Microbiota/genetics ; Sequence Analysis, DNA/methods ; *Software ; }, abstract = {MOTIVATION: The increasing amount of next-generation sequencing data poses a fundamental challenge on large scale genomic analytics. Existing tools use different distributed computational platforms to scale-out bioinformatics workloads. However, the scalability of these tools is not efficient. Moreover, they have heavy run time overheads when pre-processing large amounts of data. To address these limitations, we have developed Sparkhit: a distributed bioinformatics framework built on top of the Apache Spark platform.<br><br>RESULTS: Sparkhit integrates a variety of analytical methods. It is implemented in the Spark extended MapReduce model. It runs 92-157 times faster than MetaSpark on metagenomic fragment recruitment and 18-32 times faster than Crossbow on data pre-processing. We analyzed 100 terabytes of data across four genomic projects in the cloud in 21&#x2009;h, which includes the run times of cluster deployment and data downloading. Furthermore, our application on the entire Human Microbiome Project shotgun sequencing data was completed in 2&#x2009;h, presenting an approach to easily associate large amounts of public datasets with reference data.<br><br>Sparkhit is freely available at: https://rhinempi.github.io/sparkhit/.<br><br>CONTACT: asczyrba@cebitec.uni-bielefeld.de.<br><br>SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.}, }
@article {pmid29232932, year = {2017}, author = {Vitetta, L and Saltzman, ET and Thomsen, M and Nikov, T and Hall, S}, title = {Adjuvant Probiotics and the Intestinal Microbiome: Enhancing Vaccines and Immunotherapy Outcomes.}, journal = {Vaccines}, volume = {5}, number = {4}, pages = {}, pmid = {29232932}, issn = {2076-393X}, abstract = {Immune defence against pathogenic agents comprises the basic premise for the administration of vaccines. Vaccinations have hence prevented millions of infectious illnesses, hospitalizations and mortality. Acquired immunity comprises antibody and cell mediated responses and is characterized by its specificity and memory. Along a similar congruent yet diverse mode of disease prevention, the human host has negotiated from in utero and at birth with the intestinal commensal bacterial cohort to maintain local homeostasis in order to achieve immunological tolerance in the new born. The advent of the Human Microbiome Project has redefined an appreciation of the interactions between the host and bacteria in the intestines from one of a collection of toxic waste to one of a symbiotic existence. Probiotics comprise bacterial genera thought to provide a health benefit to the host. The intestinal microbiota has profound effects on local and extra-intestinal end organ physiology. As such, we further posit that the adjuvant administration of dedicated probiotic formulations can encourage the intestinal commensal cohort to beneficially participate in the intestinal microbiome-intestinal epithelia-innate-cell mediated immunity axes and cell mediated cellular immunity with vaccines aimed at preventing infectious diseases whilst conserving immunological tolerance. The strength of evidence for the positive effect of probiotic administration on acquired immune responses has come from various studies with viral and bacterial vaccines. We posit that the introduction early of probiotics may provide significant beneficial immune outcomes in neonates prior to commencing a vaccination schedule or in elderly adults prior to the administration of vaccinations against influenza viruses.}, }
@article {pmid29196353, year = {2017}, author = {Moffatt, MF and Cookson, WO}, title = {The lung microbiome in health and disease.}, journal = {Clinical medicine (London, England)}, volume = {17}, number = {6}, pages = {525-529}, pmid = {29196353}, issn = {1473-4893}, mesh = {Asthma/microbiology ; Bronchiectasis/microbiology ; Cystic Fibrosis/microbiology ; Humans ; Lung/*microbiology ; Lung Diseases/*microbiology ; Metagenomics ; *Microbiota/genetics ; Pulmonary Disease, Chronic Obstructive/microbiology ; RNA, Ribosomal, 16S/genetics ; }, abstract = {The Human Microbiome Project began 10 years ago, leading to a significant growth in understanding of the role the human microbiome plays in health and disease. In this article, we explain with an emphasis on the lung, the origins of microbiome research. We discuss how 16S rRNA gene sequencing became the first major molecular tool to examine the bacterial communities present within the human body. We highlight the pitfalls of molecular-based studies, such as false findings resulting from contamination, and the limitations of 16S rRNA gene sequencing. Knowledge about the lung microbiome has evolved from initial scepticism to the realisation that it might have a significant influence on many illnesses. We also discuss the lung microbiome in the context of disease by giving examples of important respiratory conditions. In addition, we draw attention to the challenges for metagenomic studies of respiratory samples and the importance of systematic bacterial isolation to enable host-microbiome interactions to be understood. We conclude by discussing how knowledge of the lung microbiome impacts current clinical diagnostics.}, }
@article {pmid29178920, year = {2017}, author = {Nash, AK and Auchtung, TA and Wong, MC and Smith, DP and Gesell, JR and Ross, MC and Stewart, CJ and Metcalf, GA and Muzny, DM and Gibbs, RA and Ajami, NJ and Petrosino, JF}, title = {The gut mycobiome of the Human Microbiome Project healthy cohort.}, journal = {Microbiome}, volume = {5}, number = {1}, pages = {153}, pmid = {29178920}, issn = {2049-2618}, support = {P30 DK056338/DK/NIDDK NIH HHS/United States ; U54 HG003273/HG/NHGRI NIH HHS/United States ; 2 U54 HG003273//National Human Genome Research Institute/ ; }, mesh = {Candida/classification/genetics/isolation &amp; purification ; Cohort Studies ; DNA, Ribosomal Spacer/genetics ; Feces/microbiology ; Fungi/classification/genetics/*isolation &amp; purification ; Gastrointestinal Microbiome/*genetics ; Genetic Variation ; *Healthy Volunteers ; High-Throughput Nucleotide Sequencing/methods ; Humans ; Malassezia/classification/genetics/isolation &amp; purification ; Metagenomics/methods ; *Microbiota ; *Mycobiome ; RNA, Ribosomal, 18S/genetics ; Saccharomyces/classification/genetics/isolation &amp; purification ; Sequence Analysis, DNA ; }, abstract = {BACKGROUND: Most studies describing the human gut microbiome in healthy and diseased states have emphasized the bacterial component, but the fungal microbiome (i.e., the mycobiome) is beginning to gain recognition as a fundamental part of our microbiome. To date, human gut mycobiome studies have primarily been disease centric or in small cohorts of healthy individuals. To contribute to existing knowledge of the human mycobiome, we investigated the gut mycobiome of the Human Microbiome Project (HMP) cohort by sequencing the Internal Transcribed Spacer 2 (ITS2) region as well as the 18S rRNA gene.<br><br>RESULTS: Three hundred seventeen HMP stool samples were analyzed by ITS2 sequencing. Fecal fungal diversity was significantly lower in comparison to bacterial diversity. Yeast dominated the samples, comprising eight of the top 15 most abundant genera. Specifically, fungal communities were characterized by a high prevalence of Saccharomyces, Malassezia, and Candida, with S. cerevisiae, M. restricta, and C. albicans operational taxonomic units (OTUs) present in 96.8, 88.3, and 80.8% of samples, respectively. There was a high degree of inter- and intra-volunteer variability in fungal communities. However, S. cerevisiae, M. restricta, and C. albicans OTUs were found in 92.2, 78.3, and 63.6% of volunteers, respectively, in all samples donated over an approximately 1-year period. Metagenomic and 18S rRNA gene sequencing data agreed with ITS2 results; however, ITS2 sequencing provided greater resolution of the relatively low abundance mycobiome constituents.<br><br>CONCLUSIONS: Compared to bacterial communities, the human gut mycobiome is low in diversity and dominated by yeast including Saccharomyces, Malassezia, and Candida. Both inter- and intra-volunteer variability in the HMP cohort were high, revealing that unlike bacterial communities, an individual's mycobiome is no more similar to itself over time than to another person's. Nonetheless, several fungal species persisted across a majority of samples, evidence that a core gut mycobiome may exist. ITS2 sequencing data provided greater resolution of the mycobiome membership compared to metagenomic and 18S rRNA gene sequencing data, suggesting that it is a more sensitive method for studying the mycobiome of stool samples.}, }
@article {pmid29177026, year = {2017}, author = {Jackson, WJ and Agarwal, I and Pe'er, I}, title = {2-Way k-Means as a Model for Microbiome Samples.}, journal = {Journal of healthcare engineering}, volume = {2017}, number = {}, pages = {5284145}, pmid = {29177026}, issn = {2040-2295}, mesh = {Algorithms ; Female ; Humans ; *Microbiota ; *Normal Distribution ; Sequence Analysis, DNA ; Vagina/microbiology ; }, abstract = {Motivation. Microbiome sequencing allows defining clusters of samples with shared composition. However, this paradigm poorly accounts for samples whose composition is a mixture of cluster-characterizing ones and which therefore lie in between them in the cluster space. This paper addresses unsupervised learning of 2-way clusters. It defines a mixture model that allows 2-way cluster assignment and describes a variant of generalized k-means for learning such a model. We demonstrate applicability to microbial 16S rDNA sequencing data from the Human Vaginal Microbiome Project.}, }
@article {pmid29152585, year = {2017}, author = {d'Hennezel, E and Abubucker, S and Murphy, LO and Cullen, TW}, title = {Total Lipopolysaccharide from the Human Gut Microbiome Silences Toll-Like Receptor Signaling.}, journal = {mSystems}, volume = {2}, number = {6}, pages = {}, pmid = {29152585}, issn = {2379-5077}, abstract = {Cohabitation of microbial communities with the host enables the formation of a symbiotic relationship that maintains homeostasis in the gut and beyond. One prevailing model suggests that this relationship relies on the capacity of host cells and tissues to remain tolerant to the strong immune stimulation generated by the microbiota such as the activation of Toll-like receptor 4 (TLR4) pathways by lipopolysaccharide (LPS). Indeed, gut microbial LPS is thought to be one of the most potent activators of innate immune signaling and an important mediator of the microbiome's influence on host physiology. In this study, we performed computational and experimental analyses of healthy human fecal samples to examine the TLR4 signaling capacity of the gut microbiota. These analyses revealed that an immunoinhibitory activity of LPS, conserved across the members of the order Bacteroidales and derived from an underacylated structural feature, silences TLR4 signaling for the entire consortium of organisms inhabiting the human gut. Comparative analysis of metagenomic data from the Human Microbiome Project and healthy-donor samples indicates that immune silencing via LPS is a microbe-intrinsic feature in all healthy adults. These findings challenge the current belief that robust TLR4 signaling is a feature of the microbiome and demonstrate that microbiome-derived LPS has the ability to facilitate host tolerance of gut microbes. These findings have broad implications for how we model host-microbe interactions and for our understanding of microbiome-linked disease. IMPORTANCE While the ability for humans to host a complex microbial ecosystem is an essential property of life, the mechanisms allowing for immune tolerance of such a large microbial load are not completely understood and are currently the focus of intense research. This study shows that an important proinflammatory pathway that is commonly triggered by pathogenic bacteria upon interaction with the host is, in fact, actively repressed by the bacteria of the gut microbiome, supporting the idea that beneficial microbes themselves contribute to the immune tolerance in support of homeostasis. These findings are important for two reasons. First, many currently assume that proinflammatory signaling by lipopolysaccharide is a fundamental feature of the gut flora. This assumption influences greatly how host-microbiome interactions are theoretically modeled but also how they are experimentally studied, by using robust TLR signaling conditions to simulate commensals. Second, elucidation of the mechanisms that support host-microbe tolerance is key to the development of therapeutics for both intestinal and systemic inflammatory disorders.}, }
@article {pmid29140991, year = {2017}, author = {Schwager, E and Mallick, H and Ventz, S and Huttenhower, C}, title = {A Bayesian method for detecting pairwise associations in compositional data.}, journal = {PLoS computational biology}, volume = {13}, number = {11}, pages = {e1005852}, pmid = {29140991}, issn = {1553-7358}, support = {R01 HG005220/HG/NHGRI NIH HHS/United States ; T32 GM074897/GM/NIGMS NIH HHS/United States ; U54 DE023798/DE/NIDCR NIH HHS/United States ; U54 DK102557/DK/NIDDK NIH HHS/United States ; }, mesh = {Algorithms ; *Bayes Theorem ; Computational Biology/*methods ; *Computer Simulation ; Ecology ; Humans ; Markov Chains ; Microbiota ; *Models, Biological ; Proteobacteria ; }, abstract = {Compositional data consist of vectors of proportions normalized to a constant sum from a basis of unobserved counts. The sum constraint makes inference on correlations between unconstrained features challenging due to the information loss from normalization. However, such correlations are of long-standing interest in fields including ecology. We propose a novel Bayesian framework (BAnOCC: Bayesian Analysis of Compositional Covariance) to estimate a sparse precision matrix through a LASSO prior. The resulting posterior, generated by MCMC sampling, allows uncertainty quantification of any function of the precision matrix, including the correlation matrix. We also use a first-order Taylor expansion to approximate the transformation from the unobserved counts to the composition in order to investigate what characteristics of the unobserved counts can make the correlations more or less difficult to infer. On simulated datasets, we show that BAnOCC infers the true network as well as previous methods while offering the advantage of posterior inference. Larger and more realistic simulated datasets further showed that BAnOCC performs well as measured by type I and type II error rates. Finally, we apply BAnOCC to a microbial ecology dataset from the Human Microbiome Project, which in addition to reproducing established ecological results revealed unique, competition-based roles for Proteobacteria in multiple distinct habitats.}, }
@article {pmid29136663, year = {2017}, author = {Zhang, Y and Alekseyenko, AV}, title = {Phylogenic inference using alignment-free methods for applications in microbial community surveys using 16s rRNA gene.}, journal = {PloS one}, volume = {12}, number = {11}, pages = {e0187940}, pmid = {29136663}, issn = {1932-6203}, support = {R01 CA164964/CA/NCI NIH HHS/United States ; R21 AR067459/AR/NIAMS NIH HHS/United States ; }, mesh = {Microbiota/*genetics ; *Phylogeny ; RNA, Ribosomal, 16S/*genetics ; }, abstract = {The diversity of microbiota is best explored by understanding the phylogenetic structure of the microbial communities. Traditionally, sequence alignment has been used for phylogenetic inference. However, alignment-based approaches come with significant challenges and limitations when massive amounts of data are analyzed. In the recent decade, alignment-free approaches have enabled genome-scale phylogenetic inference. Here we evaluate three alignment-free methods: ACS, CVTree, and Kr for phylogenetic inference with 16s rRNA gene data. We use a taxonomic gold standard to compare the accuracy of alignment-free phylogenetic inference with that of common microbiome-wide phylogenetic inference pipelines based on PyNAST and MUSCLE alignments with FastTree and RAxML. We re-simulate fecal communities from Human Microbiome Project data to evaluate the performance of the methods on datasets with properties of real data. Our comparisons show that alignment-free methods are not inferior to alignment-based methods in giving accurate and robust phylogenic trees. Moreover, consensus ensembles of alignment-free phylogenies are superior to those built from alignment-based methods in their ability to highlight community differences in low power settings. In addition, the overall running times of alignment-based and alignment-free phylogenetic inference are comparable. Taken together our empirical results suggest that alignment-free methods provide a viable approach for microbiome-wide phylogenetic inference.}, }
@article {pmid29129355, year = {2018}, author = {Li, J and Fu, R and Yang, Y and Horz, HP and Guan, Y and Lu, Y and Lou, H and Tian, L and Zheng, S and Liu, H and Shi, M and Tang, K and Wang, S and Xu, S}, title = {A metagenomic approach to dissect the genetic composition of enterotypes in Han Chinese and two Muslim groups.}, journal = {Systematic and applied microbiology}, volume = {41}, number = {1}, pages = {1-12}, doi = {10.1016/j.syapm.2017.09.006}, pmid = {29129355}, issn = {1618-0984}, mesh = {Asian People ; Bacteria/*classification/*genetics ; Cluster Analysis ; DNA, Bacterial/chemistry/genetics ; DNA, Ribosomal/chemistry/genetics ; Ethnicity ; *Gastrointestinal Microbiome ; Genetic Association Studies ; Healthy Volunteers ; Humans ; Islam ; Lysophospholipase/genetics ; *Metagenomics ; *Microbiota ; Phylogeny ; Polymorphism, Single Nucleotide ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; }, abstract = {Distinct enterotypes have been observed in the human gut but little is known about the genetic basis of the microbiome. Moreover, it is not clear how many genetic differences exist between enterotypes within or between populations. In this study, both the 16S rRNA gene and the metagenomes of the gut microbiota were sequenced from 48 Han Chinese, 48 Kazaks, and 96 Uyghurs, and taxonomies were assigned after de novo assembly. Single nucleotide polymorphisms were also identified by referring to data from the Human Microbiome Project. Systematic analysis of the gut communities in terms of their abundance and genetic composition was also performed, together with a genome-wide association study of the host genomes. The gut microbiota of 192 subjects was clearly classified into two enterotypes (Bacteroides and Prevotella). Interestingly, both enterotypes showed a clear genetic differentiation in terms of their functional catalogue of genes, especially for genes involved in amino acid and carbohydrate metabolism. In addition, several differentiated genera and genes were found among the three populations. Notably, one human variant (rs878394) was identified that showed significant association with the abundance of Prevotella, which is linked to LYPLAL1, a gene associated with body fat distribution, the waist-hip ratio and insulin sensitivity. Taken together, considerable differentiation was observed in gut microbes between enterotypes and among populations that was reflected in both the taxonomic composition and the genetic makeup of their functional genes, which could have been influenced by a variety of factors, such as diet and host genetic variation.}, }
@article {pmid29122007, year = {2017}, author = {Li, S and Fuhler, GM and Bn, N and Jose, T and Bruno, MJ and Peppelenbosch, MP and Konstantinov, SR}, title = {Pancreatic cyst fluid harbors a unique microbiome.}, journal = {Microbiome}, volume = {5}, number = {1}, pages = {147}, pmid = {29122007}, issn = {2049-2618}, mesh = {Aged ; Bacteria/classification/genetics/*isolation &amp; purification ; Bacterial Translocation ; Bacteroides/genetics/isolation &amp; purification ; DNA, Bacterial/genetics/*isolation &amp; purification ; Female ; Fusobacterium/genetics/isolation &amp; purification ; Gastrointestinal Tract/microbiology ; High-Throughput Nucleotide Sequencing ; Humans ; Male ; Microbiota/*genetics ; Middle Aged ; Neoplastic Processes ; Pancreas/microbiology/physiopathology ; Pancreatic Cyst/*microbiology ; Phylogeny ; Polymerase Chain Reaction ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Staphylococcus/genetics/isolation &amp; purification ; }, abstract = {BACKGROUND: It is clear that specific intestinal bacteria are involved in the development of different premalignant conditions along the gastrointestinal tract. An analysis of the microbial constituents in the context of pancreatic cystic lesions has, however, as yet not been performed. This consideration prompted us to explore whether endoscopically obtained pancreatic cyst fluids (PCF) contain bacterial DNA and to determine the genera of bacteria present in such material.<br><br>METHODS: Total DNA was isolated from 69 PCF samples. Bacterial 16S rRNA gene-specific PCR was performed followed by Sanger sequencing and de novo deep sequencing for the V3-V4 variable region of 16S rRNA&#xa0;gene.<br><br>RESULTS: We observed that 98.2% of the samples were positive in conventional PCR, and that 100% of selected PCF samples (n&#xa0;=&#xa0;33) were positive for bacterial microbiota as determined by next generation sequencing (NGS). Comprehensive NGS data analysis of PCF showed the presence of 408 genera of bacteria, of which 17 bacterial genera were uniquely abundant to PCF, when compared to the Human Microbiome Project (HMP) database and 15 bacterial microbiota were uniquely abundant in HMP only. Bacteroides spp., Escherichia/Shigella spp., and Acidaminococcus spp. which were predominant in PCF, while also a substantial Staphylococcus spp. and Fusobacterium spp. component was detected.<br><br>CONCLUSION: These results reveal and characterize an apparently specific bacterial ecosystem in pancreatic cyst fluid samples and may reflect the local microbiota in the pancreas. Some taxa with potential deleterious functions are present in the bacterial abundance profiles, suggesting that the unique microbiome in this specific niche may contribute to neoplastic processes in the pancreas. Further studies are needed to explore the intricate relationship between pathophysiological status in the host pancreas and its microbiota.}, }
@article {pmid29106667, year = {2018}, author = {Oliveira, FS and Brestelli, J and Cade, S and Zheng, J and Iodice, J and Fischer, S and Aurrecoechea, C and Kissinger, JC and Brunk, BP and Stoeckert, CJ and Fernandes, GR and Roos, DS and Beiting, DP}, title = {MicrobiomeDB: a systems biology platform for integrating, mining and analyzing microbiome experiments.}, journal = {Nucleic acids research}, volume = {46}, number = {D1}, pages = {D684-D691}, pmid = {29106667}, issn = {1362-4962}, mesh = {Animals ; Computer Simulation ; Data Mining/*methods ; *Databases, Genetic ; Datasets as Topic ; Environmental Microbiology ; Genetic Variation ; Humans ; Internet ; *Microbiota ; Mobile Applications ; *Systems Biology ; User-Computer Interface ; Workflow ; }, abstract = {MicrobiomeDB (http://microbiomeDB.org) is a data discovery and analysis platform that empowers researchers to fully leverage experimental variables to interrogate microbiome datasets. MicrobiomeDB was developed in collaboration with the Eukaryotic Pathogens Bioinformatics Resource Center (http://EuPathDB.org) and leverages the infrastructure and user interface of EuPathDB, which allows users to construct in silico experiments using an intuitive graphical 'strategy' approach. The current release of the database integrates microbial census data with sample details for nearly 14 000 samples originating from human, animal and environmental sources, including over 9000 samples from healthy human subjects in the Human Microbiome Project (http://portal.ihmpdcc.org/). Query results can be statistically analyzed and graphically visualized via interactive web applications launched directly in the browser, providing insight into microbial community diversity and allowing users to identify taxa associated with any experimental covariate.}, }
@article {pmid29088705, year = {2017}, author = {Thompson, LR and Sanders, JG and McDonald, D and Amir, A and Ladau, J and Locey, KJ and Prill, RJ and Tripathi, A and Gibbons, SM and Ackermann, G and Navas-Molina, JA and Janssen, S and Kopylova, E and Vázquez-Baeza, Y and González, A and Morton, JT and Mirarab, S and Zech Xu, Z and Jiang, L and Haroon, MF and Kanbar, J and Zhu, Q and Jin Song, S and Kosciolek, T and Bokulich, NA and Lefler, J and Brislawn, CJ and Humphrey, G and Owens, SM and Hampton-Marcell, J and Berg-Lyons, D and McKenzie, V and Fierer, N and Fuhrman, JA and Clauset, A and Stevens, RL and Shade, A and Pollard, KS and Goodwin, KD and Jansson, JK and Gilbert, JA and Knight, R and , }, title = {A communal catalogue reveals Earth's multiscale microbial diversity.}, journal = {Nature}, volume = {551}, number = {7681}, pages = {457-463}, pmid = {29088705}, issn = {1476-4687}, support = {R01 AI123037/AI/NIAID NIH HHS/United States ; R01 DE024463/DE/NIDCR NIH HHS/United States ; }, mesh = {Animals ; Archaea/genetics/isolation &amp; purification ; Bacteria/genetics/isolation &amp; purification ; *Biodiversity ; *Earth, Planet ; Ecology/methods ; Gene Dosage ; Geographic Mapping ; Humans ; Microbiota/*genetics ; Plants/microbiology ; RNA, Ribosomal, 16S/analysis/genetics ; }, abstract = {Our growing awareness of the microbial world's importance and diversity contrasts starkly with our limited understanding of its fundamental structure. Despite recent advances in DNA sequencing, a lack of standardized protocols and common analytical frameworks impedes comparisons among studies, hindering the development of global inferences about microbial life on Earth. Here we present a meta-analysis of microbial community samples collected by hundreds of researchers for the Earth Microbiome Project. Coordinated protocols and new analytical methods, particularly the use of exact sequences instead of clustered operational taxonomic units, enable bacterial and archaeal ribosomal RNA gene sequences to be followed across multiple studies and allow us to explore patterns of diversity at an unprecedented scale. The result is both a reference database giving global context to DNA sequence data and a framework for incorporating data from future studies, fostering increasingly complete characterization of Earth's microbial diversity.}, }
@article {pmid29062070, year = {2018}, author = {Cookson, WOCM and Cox, MJ and Moffatt, MF}, title = {New opportunities for managing acute and chronic lung infections.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {2}, pages = {111-120}, pmid = {29062070}, issn = {1740-1534}, support = {G1000758/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Acute Disease ; Anti-Bacterial Agents/*therapeutic use ; Bacterial Infections/*drug therapy/*microbiology ; Chronic Disease ; Drug Resistance, Bacterial ; Global Health ; Humans ; Lung/microbiology ; Lung Diseases/*drug therapy/*microbiology ; Microbiota ; }, abstract = {Lung diseases caused by microbial infections affect hundreds of millions of children and adults throughout the world. In Western populations, the treatment of lung infections is a primary driver of antibiotic resistance. Traditional therapeutic strategies have been based on the premise that the healthy lung is sterile and that infections grow in a pristine environment. As a consequence, rapid advances in our understanding of the composition of the microbiota of the skin and bowel have not yet been matched by studies of the respiratory tree. The recognition that the lungs are as populated with microorganisms as other mucosal surfaces provides the opportunity to reconsider the mechanisms and management of lung infections. Molecular analyses of the lung microbiota are revealing profound adverse responses to widespread antibiotic use, urbanization and globalization. This Opinion article proposes how technologies and concepts flowing from the Human Microbiome Project can transform the diagnosis and treatment of common lung diseases.}, }
@article {pmid29038470, year = {2017}, author = {Ma, ZS and Ye, D}, title = {Trios-promising in silico biomarkers for differentiating the effect of disease on the human microbiome network.}, journal = {Scientific reports}, volume = {7}, number = {1}, pages = {13259}, pmid = {29038470}, issn = {2045-2322}, mesh = {Biomarkers/*metabolism ; Humans ; Microbiota/genetics/*physiology ; *Models, Theoretical ; }, abstract = {Recent advances in the HMP (human microbiome project) research have revealed profound implications of the human microbiome to our health and diseases. We postulated that there should be distinctive features associated with healthy and/or diseased microbiome networks. Following Occam's razor principle, we further hypothesized that triangle motifs or trios, arguably the simplest motif in a complex network of the human microbiome, should be sufficient to detect changes that occurred in the diseased microbiome. Here we test our hypothesis with six HMP datasets that cover five major human microbiome sites (gut, lung, oral, skin, and vaginal). The tests confirm our hypothesis and demonstrate that the trios involving the special nodes (e.g., most abundant OTU or MAO, and most dominant OTU or MDO, etc.) and interactions types (positive vs. negative) can be a powerful tool to differentiate between healthy and diseased microbiome samples. Our findings suggest that 12 kinds of trios (especially, dominantly inhibitive trio with mixed strategy, dominantly inhibitive trio with pure strategy, and fully facilitative strategy) may be utilized as in silico biomarkers for detecting disease-associated changes in the human microbiome, and may play an important role in personalized precision diagnosis of the human microbiome associated diseases.}, }
@article {pmid29028892, year = {2018}, author = {Weber, N and Liou, D and Dommer, J and MacMenamin, P and Quiñones, M and Misner, I and Oler, AJ and Wan, J and Kim, L and Coakley McCarthy, M and Ezeji, S and Noble, K and Hurt, DE}, title = {Nephele: a cloud platform for simplified, standardized and reproducible microbiome data analysis.}, journal = {Bioinformatics (Oxford, England)}, volume = {34}, number = {8}, pages = {1411-1413}, pmid = {29028892}, issn = {1367-4811}, mesh = {*Cloud Computing ; Computational Biology/*methods ; Humans ; Metagenomics/methods ; Microbiota/*genetics ; Sequence Analysis, DNA/methods ; Sequence Analysis, RNA ; *Software ; }, abstract = {MOTIVATION: Widespread interest in the study of the microbiome has resulted in data proliferation and the development of powerful computational tools. However, many scientific researchers lack the time, training, or infrastructure to work with large datasets or to install and use command line tools.<br><br>RESULTS: The National Institute of Allergy and Infectious Diseases (NIAID) has created Nephele, a cloud-based microbiome data analysis platform with standardized pipelines and a simple web interface for transforming raw data into biological insights. Nephele integrates common microbiome analysis tools as well as valuable reference datasets like the healthy human subjects cohort of the Human Microbiome Project (HMP). Nephele is built on the Amazon Web Services cloud, which provides centralized and automated storage and compute capacity, thereby reducing the burden on researchers and their institutions.<br><br>https://nephele.niaid.nih.gov and https://github.com/niaid/Nephele.<br><br>CONTACT: darrell.hurt@nih.gov.}, }
@article {pmid29022944, year = {2017}, author = {Lloyd-Price, J and Mahurkar, A and Rahnavard, G and Crabtree, J and Orvis, J and Hall, AB and Brady, A and Creasy, HH and McCracken, C and Giglio, MG and McDonald, D and Franzosa, EA and Knight, R and White, O and Huttenhower, C}, title = {Erratum: Strains, functions and dynamics in the expanded Human Microbiome Project.}, journal = {Nature}, volume = {551}, number = {7679}, pages = {256}, pmid = {29022944}, issn = {1476-4687}, abstract = {This corrects the article DOI: 10.1038/nature23889.}, }
@article {pmid29020741, year = {2017}, author = {Moitinho-Silva, L and Nielsen, S and Amir, A and Gonzalez, A and Ackermann, GL and Cerrano, C and Astudillo-Garcia, C and Easson, C and Sipkema, D and Liu, F and Steinert, G and Kotoulas, G and McCormack, GP and Feng, G and Bell, JJ and Vicente, J and Björk, JR and Montoya, JM and Olson, JB and Reveillaud, J and Steindler, L and Pineda, MC and Marra, MV and Ilan, M and Taylor, MW and Polymenakou, P and Erwin, PM and Schupp, PJ and Simister, RL and Knight, R and Thacker, RW and Costa, R and Hill, RT and Lopez-Legentil, S and Dailianis, T and Ravasi, T and Hentschel, U and Li, Z and Webster, NS and Thomas, T}, title = {The sponge microbiome project.}, journal = {GigaScience}, volume = {6}, number = {10}, pages = {1-7}, pmid = {29020741}, issn = {2047-217X}, mesh = {Animals ; *Microbiota ; Porifera/*microbiology ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; }, abstract = {Marine sponges (phylum Porifera) are a diverse, phylogenetically deep-branching clade known for forming intimate partnerships with complex communities of microorganisms. To date, 16S rRNA gene sequencing studies have largely utilised different extraction and amplification methodologies to target the microbial communities of a limited number of sponge species, severely limiting comparative analyses of sponge microbial diversity and structure. Here, we provide an extensive and standardised dataset that will facilitate sponge microbiome comparisons across large spatial, temporal, and environmental scales. Samples from marine sponges (n = 3569 specimens), seawater (n = 370), marine sediments (n = 65) and other environments (n = 29) were collected from different locations across the globe. This dataset incorporates at least 268 different sponge species, including several yet unidentified taxa. The V4 region of the 16S rRNA gene was amplified and sequenced from extracted DNA using standardised procedures. Raw sequences (total of 1.1 billion sequences) were processed and clustered with (i) a standard protocol using QIIME closed-reference picking resulting in 39 543 operational taxonomic units (OTU) at 97% sequence identity, (ii) a de novo clustering using Mothur resulting in 518 246 OTUs, and (iii) a new high-resolution Deblur protocol resulting in 83 908 unique bacterial sequences. Abundance tables, representative sequences, taxonomic classifications, and metadata are provided. This dataset represents a comprehensive resource of sponge-associated microbial communities based on 16S rRNA gene sequences that can be used to address overarching hypotheses regarding host-associated prokaryotes, including host specificity, convergent evolution, environmental drivers of microbiome structure, and the sponge-associated rare biosphere.}, }
@article {pmid28978331, year = {2017}, author = {Shamarina, D and Stoyantcheva, I and Mason, CE and Bibby, K and Elhaik, E}, title = {Communicating the promise, risks, and ethics of large-scale, open space microbiome and metagenome research.}, journal = {Microbiome}, volume = {5}, number = {1}, pages = {132}, pmid = {28978331}, issn = {2049-2618}, support = {R01 ES021006/ES/NIEHS NIH HHS/United States ; R25 EB020393/EB/NIBIB NIH HHS/United States ; }, mesh = {Environment Design ; *Ethics, Research ; Humans ; *Metagenome ; Metagenomics ; *Microbiota ; Public Opinion ; *Public Relations ; *Research ; }, abstract = {The public commonly associates microorganisms with pathogens. This suspicion of microorganisms is understandable, as historically microorganisms have killed more humans than any other agent while remaining largely unknown until the late seventeenth century with the works of van Leeuwenhoek and Kircher. Despite our improved understanding regarding microorganisms, the general public are apt to think of diseases rather than of the majority of harmless or beneficial species that inhabit our bodies and the built and natural environment. As long as microbiome research was confined to labs, the public's exposure to microbiology was limited. The recent launch of global microbiome surveys, such as the Earth Microbiome Project and MetaSUB (Metagenomics and Metadesign of Subways and Urban Biomes) project, has raised ethical, financial, feasibility, and sustainability concerns as to the public's level of understanding and potential reaction to the findings, which, done improperly, risk negative implications for ongoing and future investigations, but done correctly, can facilitate a new vision of "smart cities." To facilitate improved future research, we describe here the major concerns that our discussions with ethics committees, community leaders, and government officials have raised, and we expound on how to address them. We further discuss ethical considerations of microbiome surveys and provide practical recommendations for public engagement.}, }
@article {pmid28961122, year = {2020}, author = {Ma, Y and Hu, X and He, T and Jiang, X}, title = {Clustering and Integrating of Heterogeneous Microbiome Data by Joint Symmetric Nonnegative Matrix Factorization with Laplacian Regularization.}, journal = {IEEE/ACM transactions on computational biology and bioinformatics}, volume = {17}, number = {3}, pages = {788-795}, doi = {10.1109/TCBB.2017.2756628}, pmid = {28961122}, issn = {1557-9964}, mesh = {*Cluster Analysis ; Computational Biology/*methods ; Databases, Genetic ; Humans ; Microbiota/*genetics ; Phylogeny ; Statistics as Topic ; }, abstract = {Many datasets that exists in the real world are often comprised of different representations or views which provide complementary information to each other. To integrate information from multiple views, data integration approaches such as nonnegative matrix factorization (NMF) have been developed to combine multiple heterogeneous data simultaneously to obtain a comprehensive representation. In this paper, we proposed a novel variant of symmetric nonnegative matrix factorization (SNMF), called Laplacian regularization based joint symmetric nonnegative matrix factorization (LJ-SNMF) for clustering multi-view data. We conduct extensive experiments on several realistic datasets including Human Microbiome Project data. The experimental results show that the proposed method outperforms other variants of NMF, which suggests the potential application of LJ-SNMF in clustering multi-view datasets. Additionally, we also demonstrate the capability of LJ-SNMF in community finding.}, }
@article {pmid28953883, year = {2017}, author = {Lloyd-Price, J and Mahurkar, A and Rahnavard, G and Crabtree, J and Orvis, J and Hall, AB and Brady, A and Creasy, HH and McCracken, C and Giglio, MG and McDonald, D and Franzosa, EA and Knight, R and White, O and Huttenhower, C}, title = {Strains, functions and dynamics in the expanded Human Microbiome Project.}, journal = {Nature}, volume = {550}, number = {7674}, pages = {61-66}, pmid = {28953883}, issn = {1476-4687}, support = {U54 HG004973/HG/NHGRI NIH HHS/United States ; U54 DK102557/DK/NIDDK NIH HHS/United States ; P30 DK043351/DK/NIDDK NIH HHS/United States ; U01 HG006537/HG/NHGRI NIH HHS/United States ; U54 AI084844/AI/NIAID NIH HHS/United States ; U01 HG004866/HG/NHGRI NIH HHS/United States ; U54 HG004968/HG/NHGRI NIH HHS/United States ; R01 HG004872/HG/NHGRI NIH HHS/United States ; U54 HG003079/HG/NHGRI NIH HHS/United States ; U54 HG004969/HG/NHGRI NIH HHS/United States ; }, mesh = {Datasets as Topic ; Humans ; Metagenome/genetics/physiology ; Microbiota/genetics/*physiology ; Molecular Sequence Annotation ; National Institutes of Health (U.S.) ; Organ Specificity ; *Phylogeny ; Spatio-Temporal Analysis ; Time Factors ; United States ; }, abstract = {The characterization of baseline microbial and functional diversity in the human microbiome has enabled studies of microbiome-related disease, diversity, biogeography, and molecular function. The National Institutes of Health Human Microbiome Project has provided one of the broadest such characterizations so far. Here we introduce a second wave of data from the study, comprising 1,631 new metagenomes (2,355 total) targeting diverse body sites with multiple time points in 265 individuals. We applied updated profiling and assembly methods to provide new characterizations of microbiome personalization. Strain identification revealed subspecies clades specific to body sites; it also quantified species with phylogenetic diversity under-represented in isolate genomes. Body-wide functional profiling classified pathways into universal, human-enriched, and body site-enriched subsets. Finally, temporal analysis decomposed microbial variation into rapidly variable, moderately variable, and stable subsets. This study furthers our knowledge of baseline human microbial diversity and enables an understanding of personalized microbiome function and dynamics.}, }
@article {pmid28915922, year = {2017}, author = {Winglee, K and Howard, AG and Sha, W and Gharaibeh, RZ and Liu, J and Jin, D and Fodor, AA and Gordon-Larsen, P}, title = {Recent urbanization in China is correlated with a Westernized microbiome encoding increased virulence and antibiotic resistance genes.}, journal = {Microbiome}, volume = {5}, number = {1}, pages = {121}, pmid = {28915922}, issn = {2049-2618}, support = {R01 DK104371/DK/NIDDK NIH HHS/United States ; R01 HL108427/HL/NHLBI NIH HHS/United States ; R24 HD050924/HD/NICHD NIH HHS/United States ; UL1 TR001111/TR/NCATS NIH HHS/United States ; P30 ES010126/ES/NIEHS NIH HHS/United States ; }, mesh = {Aged ; Bacteria/*genetics/pathogenicity ; China ; *Diet, Western ; Drug Resistance, Microbial/*genetics ; Escherichia coli/genetics/pathogenicity ; Feeding Behavior ; Female ; *Gastrointestinal Microbiome/genetics ; Genetic Variation ; High-Throughput Nucleotide Sequencing ; Humans ; Male ; *Metabolome ; Metagenomics ; Middle Aged ; Shigella/genetics/pathogenicity ; *Urbanization ; Virulence/genetics ; }, abstract = {BACKGROUND: Urbanization is associated with an increased risk for a number of diseases, including obesity, diabetes, and cancer, which all also show associations with the microbiome. While microbial community composition has been shown to vary across continents and in traditional versus Westernized societies, few studies have examined urban-rural differences in neighboring communities within a single country undergoing rapid urbanization. In this study, we compared the gut microbiome, plasma metabolome, dietary habits, and health biomarkers of rural and urban people from a single Chinese province.<br><br>RESULTS: We identified significant differences in the microbiota and microbiota-related plasma metabolites in rural versus recently urban subjects from the Hunan province of China. Microbes with higher relative abundance in Chinese urban samples have been associated with disease in other studies and were substantially more prevalent in the Human Microbiome Project cohort of American subjects. Furthermore, using whole metagenome sequencing, we found that urbanization was associated with a loss of microbial diversity and changes in the relative abundances of Viruses, Archaea, and Bacteria. Gene diversity, however, increased with urbanization, along with the proportion of reads associated with antibiotic resistance and virulence, which were strongly correlated with the presence of Escherichia and Shigella.<br><br>CONCLUSIONS: Our data suggest that urbanization has produced convergent evolution of the gut microbial composition in American and urban Chinese populations, resulting in similar compositional patterns of abundant microbes through similar lifestyles on different continents, including a loss of potentially beneficial bacteria and an increase in potentially harmful genes via increased relative abundance of Escherichia and Shigella.}, }
@article {pmid28846702, year = {2017}, author = {Abdelmaksoud, AA and Girerd, PH and Garcia, EM and Brooks, JP and Leftwich, LM and Sheth, NU and Bradley, SP and Serrano, MG and Fettweis, JM and Huang, B and Strauss, JF and Buck, GA and Jefferson, KK}, title = {Association between statin use, the vaginal microbiome, and Gardnerella vaginalis vaginolysin-mediated cytotoxicity.}, journal = {PloS one}, volume = {12}, number = {8}, pages = {e0183765}, pmid = {28846702}, issn = {1932-6203}, support = {P60 MD002256/MD/NIMHD NIH HHS/United States ; U54 DE023786/DE/NIDCR NIH HHS/United States ; UH3 AI083263/AI/NIAID NIH HHS/United States ; }, mesh = {Bacterial Proteins/*physiology ; Bacterial Toxins ; Cell Survival/*physiology ; Colony Count, Microbial ; Epithelial Cells/metabolism ; Female ; Gardnerella vaginalis/isolation &amp; purification/*metabolism ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/*pharmacology ; Microbiota/*drug effects/genetics ; Middle Aged ; RNA, Ribosomal, 16S/genetics ; Simvastatin/*pharmacology ; Vagina/*microbiology ; }, abstract = {BACKGROUND: Bacterial vaginosis (BV) is the leading dysbiosis of the vaginal microbiome. The pathways leading towards the development of BV are not well understood. Gardnerella vaginalis is frequently associated with BV. G. vaginalis produces the cholesterol-dependent cytolysin (CDC), vaginolysin, which can lyse a variety of human cells and is thought to play a role in pathogenesis. Because membrane cholesterol is required for vaginolysin to function, and because HMG-CoA reductase inhibitors (statins) affect not only serum levels of cholesterol but membrane levels as well, we hypothesized that statins might affect the vaginal microbiome.<br><br>METHODS: To investigate the relationship between use of the statins and the vaginal microbiome, we analyzed 16S rRNA gene taxonomic surveys performed on vaginal samples from 133 women who participated in the Vaginal Human Microbiome Project and who were taking statins at the time of sampling, 152 women who reported high cholesterol levels but were not taking statins, and 316 women who did not report high cholesterol. To examine the effect of statins on the cytolytic effect of vaginolysin, the cholesterol-dependent cytolysin (CDC) produced by Gardnerella vaginalis, we assessed the effect of simvastatin pretreatment of VK2E6/E7 vaginal epithelial cells on vaginolysin-mediated cytotoxicity.<br><br>RESULTS: The mean proportion of G. vaginalis among women taking statins was significantly lower relative to women not using statins. Women using statins had higher mean proportions of Lactobacillus crispatus relative to women with normal cholesterol levels, and higher levels of Lactobacillus jensenii relative to women with high cholesterol but not taking statins. In vitro, vaginal epithelial cells pretreated with simvastatin were relatively resistant to vaginolysin and this effect was inhibited by cholesterol.<br><br>CONCLUSIONS: In this cross-sectional study, statin use was associated with reduced proportions of G. vaginalis and greater proportions of beneficial lactobacilli within the vaginal microbiome. The negative association between statin use and G. vaginalis may be related to inhibition of vaginolysin function.}, }
@article {pmid28842845, year = {2017}, author = {Li, DY and Tang, WHW}, title = {Gut Microbiota and Atherosclerosis.}, journal = {Current atherosclerosis reports}, volume = {19}, number = {10}, pages = {39}, doi = {10.1007/s11883-017-0675-9}, pmid = {28842845}, issn = {1534-6242}, mesh = {Animals ; *Atherosclerosis/drug therapy/metabolism/microbiology ; Bile Acids and Salts/metabolism ; Carnitine/metabolism ; Diet ; Disease Models, Animal ; *Gastrointestinal Microbiome/immunology ; Humans ; Methylamines/*metabolism ; }, abstract = {PURPOSE OF REVIEW: Studies in microbiota-mediated health risks have gained traction in recent years since the compilation of the Human Microbiome Project. No longer do we believe that our gut microbiota is an inert set of microorganisms that reside in the body without consequence. In this review, we discuss the recent findings which further our understanding of the connection between the gut microbiota and the atherosclerosis.<br><br>RECENT FINDINGS: We evaluate studies which illustrate the current understanding of the relationship between infection, immunity, altered metabolism, and bacterial products such as immune activators or dietary metabolites and their contributions to the development of atherosclerosis. In particular, we critically examine rec ent clinical and mechanistic findings for the novel microbiota-dependent dietary metabolite, trimethylamine N-oxide (TMAO), which has been implicated in atherosclerosis. These discoveries are now becoming integrated with advances in microbiota profiling which enhance our ability to interrogate the functional role of the gut microbiome and develop strategies for targeted therapeutics. The gut microbiota is a multi-faceted system that is unraveling novel contributors to the development and progression of atherosclerosis. In this review, we discuss historic and novel contributors while highlighting the TMAO story mainly as an example of the various paths taken beyond deciphering microbial composition to elucidate downstream mechanisms that promote (or protect from) atherogenesis in the hopes of translating these findings from bench to bedside.}, }
@article {pmid28771841, year = {2017}, author = {Boost, M and Cho, P and Wang, Z}, title = {Disturbing the balance: effect of contact lens use on the ocular proteome and microbiome.}, journal = {Clinical &amp; experimental optometry}, volume = {100}, number = {5}, pages = {459-472}, doi = {10.1111/cxo.12582}, pmid = {28771841}, issn = {1444-0938}, mesh = {Contact Lenses/*statistics &amp; numerical data ; Cornea/*metabolism ; Humans ; Microbiota/*physiology ; Proteome/*metabolism ; Proteostasis/*physiology ; Refractive Errors/therapy ; Tears/*metabolism ; Vision Disorders/therapy ; }, abstract = {Contact lens wear is a popular, convenient and effective method for vision correction. In recent years, contact lens practice has expanded to include new paradigms, including orthokeratology; however, their use is not entirely without risk, as the incidence of infection has consistently been reported to be higher in contact lens wearers. The explanations for this increased susceptibility have largely focused on physical damage, especially to the cornea, due to a combination of hypoxia, mechanical trauma, deposits and solution cytotoxicity, as well as poor compliance with care routines leading to introduction of pathogens into the ocular environment. However, in recent years, with the increasing availability and reduced cost of molecular techniques, the ocular environment has received greater attention with in-depth studies of proteins and other components. Numerous proteins were found to be present in the tears and their functions and interactions indicate that the tears are far more complex than formerly presumed. In addition, the concept of a sterile or limited microbial population on the ocular surface has been challenged by analysis of the microbiome. Ocular microbiome was not considered as one of the key sites for the Human Microbiome Project, as it was thought to be limited compared to other body sites. This was proven to be fallacious, as a wide variety of micro-organisms were identified in the analyses of human tears. Thus, the ocular environment is now recognised to be more complicated and interference with this ecological balance may lead to adverse effects. The use of contact lenses clearly changes the situation at the ocular surface, which may result in consequences which disturb the balance in the healthy eye.}, }
@article {pmid28769875, year = {2017}, author = {Vecchio-Pagan, B and Bewick, S and Mainali, K and Karig, DK and Fagan, WF}, title = {A Stoichioproteomic Analysis of Samples from the Human Microbiome Project.}, journal = {Frontiers in microbiology}, volume = {8}, number = {}, pages = {1119}, pmid = {28769875}, issn = {1664-302X}, abstract = {Ecological stoichiometry (ES) uses organism-specific elemental content to explain differences in species life histories, species interactions, community organization, environmental constraints and even ecosystem function. Although ES has been successfully applied to a range of different organisms, most emphasis on microbial ecological stoichiometry focuses on lake, ocean, and soil communities. With the recent advances in human microbiome research, however, large amounts of data are being generated that describe differences in community composition across body sites and individuals. We suggest that ES may provide a framework for beginning to understand the structure, organization, and function of human microbial communities, including why certain organisms exist at certain locations, and how they interact with both the other microbes in their environment and their human host. As a first step, we undertake a stoichioproteomic analysis of microbial communities from different body sites. Specifically, we compare and contrast the elemental composition of microbial protein samples using annotated sequencing data from 690 gut, vaginal, oral, nares, and skin samples currently available through the Human Microbiome Project. Our results suggest significant differences in both the median and variance of the carbon, oxygen, nitrogen, and sulfur contents of microbial protein samples from different locations. For example, whereas proteins from vaginal sites are high in carbon, proteins from skin and nasal sites are high in nitrogen and oxygen. Meanwhile, proteins from stool (the gut) are particularly high in sulfur content. We interpret these differences in terms of the local environments at different human body sites, including atmospheric exposure and food intake rates.}, }
@article {pmid28761932, year = {2017}, author = {Dheilly, NM and Bolnick, D and Bordenstein, S and Brindley, PJ and Figuères, C and Holmes, EC and Martínez Martínez, J and Phillips, AJ and Poulin, R and Rosario, K}, title = {Parasite Microbiome Project: Systematic Investigation of Microbiome Dynamics within and across Parasite-Host Interactions.}, journal = {mSystems}, volume = {2}, number = {4}, pages = {}, pmid = {28761932}, issn = {2379-5077}, support = {P30 DK058404/DK/NIDDK NIH HHS/United States ; }, abstract = {Understanding how microbiomes affect host resistance, parasite virulence, and parasite-associated diseases requires a collaborative effort between parasitologists, microbial ecologists, virologists, and immunologists. We hereby propose the Parasite Microbiome Project to bring together researchers with complementary expertise and to study the role of microbes in host-parasite interactions. Data from the Parasite Microbiome Project will help identify the mechanisms driving microbiome variation in parasites and infected hosts and how that variation is associated with the ecology and evolution of parasites and their disease outcomes. This is a call to arms to prevent fragmented research endeavors, encourage best practices in experimental approaches, and allow reliable comparative analyses across model systems. It is also an invitation to foundations and national funding agencies to propel the field of parasitology into the microbiome/metagenomic era.}, }
@article {pmid28730144, year = {2017}, author = {Yu, G and Torres, J and Hu, N and Medrano-Guzman, R and Herrera-Goepfert, R and Humphrys, MS and Wang, L and Wang, C and Ding, T and Ravel, J and Taylor, PR and Abnet, CC and Goldstein, AM}, title = {Molecular Characterization of the Human Stomach Microbiota in Gastric Cancer Patients.}, journal = {Frontiers in cellular and infection microbiology}, volume = {7}, number = {}, pages = {302}, pmid = {28730144}, issn = {2235-2988}, mesh = {Adult ; Aged ; Bacteria/classification/genetics/*isolation &amp; purification ; China ; Female ; *Gastrointestinal Microbiome ; Helicobacter pylori/classification/genetics/isolation &amp; purification ; Humans ; Male ; Mexico ; Middle Aged ; Stomach/*microbiology ; Stomach Neoplasms/*microbiology ; Young Adult ; }, abstract = {Helicobacter pylori (Hp) is the primary cause of gastric cancer but we know little of its relative abundance and other microbes in the stomach, especially at the time of gastric cancer diagnosis. Here we characterized the taxonomic and derived functional profiles of gastric microbiota in two different sets of gastric cancer patients, and compared them with microbial profiles in other body sites. Paired non-malignant and tumor tissues were sampled from 160 gastric cancer patients with 80 from China and 80 from Mexico. The 16S rRNA gene V3-V4 region was sequenced using MiSeq platform for taxonomic profiles. PICRUSt was used to predict functional profiles. Human Microbiome Project was used for comparison. We showed that Hp is the most abundant member of gastric microbiota in both Chinese and Mexican samples (51 and 24%, respectively), followed by oral-associated bacteria. Taxonomic (phylum-level) profiles of stomach microbiota resembled oral microbiota, especially when the Helicobacter reads were removed. The functional profiles of stomach microbiota, however, were distinct from those found in other body sites and had higher inter-subject dissimilarity. Gastric microbiota composition did not differ by Hp colonization status or stomach anatomic sites, but did differ between paired non-malignant and tumor tissues in either Chinese or Mexican samples. Our study showed that Hp is the dominant member of the non-malignant gastric tissue microbiota in many gastric cancer patients. Our results provide insights on the gastric microbiota composition and function in gastric cancer patients, which may have important clinical implications.}, }
@article {pmid28578872, year = {2017}, author = {Pollet, RM and D'Agostino, EH and Walton, WG and Xu, Y and Little, MS and Biernat, KA and Pellock, SJ and Patterson, LM and Creekmore, BC and Isenberg, HN and Bahethi, RR and Bhatt, AP and Liu, J and Gharaibeh, RZ and Redinbo, MR}, title = {An Atlas of β-Glucuronidases in the Human Intestinal Microbiome.}, journal = {Structure (London, England : 1993)}, volume = {25}, number = {7}, pages = {967-977.e5}, pmid = {28578872}, issn = {1878-4186}, support = {P30 ES010126/ES/NIEHS NIH HHS/United States ; T32 GM008570/GM/NIGMS NIH HHS/United States ; R01 CA161879/CA/NCI NIH HHS/United States ; R01 HL094463/HL/NHLBI NIH HHS/United States ; R01 CA207416/CA/NCI NIH HHS/United States ; T32 DK007737/DK/NIDDK NIH HHS/United States ; U01 GM102137/GM/NIGMS NIH HHS/United States ; R01 CA098468/CA/NCI NIH HHS/United States ; }, mesh = {Bacterial Proteins/*chemistry/classification/genetics/metabolism ; *Gastrointestinal Microbiome ; Glucuronidase/*chemistry/classification/genetics/metabolism ; Humans ; }, abstract = {Microbiome-encoded β-glucuronidase (GUS) enzymes play important roles in human health by metabolizing drugs in the gastrointestinal (GI) tract. The numbers, types, and diversity of these proteins in the human GI microbiome, however, remain undefined. We present an atlas of GUS enzymes comprehensive for the Human Microbiome Project GI database. We identify 3,013 total and 279 unique microbiome-encoded GUS proteins clustered into six unique structural categories. We assign their taxonomy, assess cellular localization, reveal the inter-individual variability within the 139 individuals sampled, and discover 112 novel microbial GUS enzymes. A representative in vitro panel of the most common GUS proteins by read abundances highlights structural and functional variabilities within the family, including their differential processing of smaller glucuronides and larger carbohydrates. These data provide a sequencing-to-molecular roadmap for examining microbiome-encoded enzymes essential to human health.}, }
@article {pmid28533766, year = {2017}, author = {Moitinho-Silva, L and Steinert, G and Nielsen, S and Hardoim, CCP and Wu, YC and McCormack, GP and López-Legentil, S and Marchant, R and Webster, N and Thomas, T and Hentschel, U}, title = {Predicting the HMA-LMA Status in Marine Sponges by Machine Learning.}, journal = {Frontiers in microbiology}, volume = {8}, number = {}, pages = {752}, pmid = {28533766}, issn = {1664-302X}, abstract = {The dichotomy between high microbial abundance (HMA) and low microbial abundance (LMA) sponges has been observed in sponge-microbe symbiosis, although the extent of this pattern remains poorly unknown. We characterized the differences between the microbiomes of HMA (n = 19) and LMA (n = 17) sponges (575 specimens) present in the Sponge Microbiome Project. HMA sponges were associated with richer and more diverse microbiomes than LMA sponges, as indicated by the comparison of alpha diversity metrics. Microbial community structures differed between HMA and LMA sponges considering Operational Taxonomic Units (OTU) abundances and across microbial taxonomic levels, from phylum to species. The largest proportion of microbiome variation was explained by the host identity. Several phyla, classes, and OTUs were found differentially abundant in either group, which were considered "HMA indicators" and "LMA indicators." Machine learning algorithms (classifiers) were trained to predict the HMA-LMA status of sponges. Among nine different classifiers, higher performances were achieved by Random Forest trained with phylum and class abundances. Random Forest with optimized parameters predicted the HMA-LMA status of additional 135 sponge species (1,232 specimens) without a priori knowledge. These sponges were grouped in four clusters, from which the largest two were composed of species consistently predicted as HMA (n = 44) and LMA (n = 74). In summary, our analyses shown distinct features of the microbial communities associated with HMA and LMA sponges. The prediction of the HMA-LMA status based on the microbiome profiles of sponges demonstrates the application of machine learning to explore patterns of host-associated microbial communities.}, }
@article {pmid28506279, year = {2017}, author = {Rath, S and Heidrich, B and Pieper, DH and Vital, M}, title = {Uncovering the trimethylamine-producing bacteria of the human gut microbiota.}, journal = {Microbiome}, volume = {5}, number = {1}, pages = {54}, pmid = {28506279}, issn = {2049-2618}, mesh = {Bacteria/*classification/enzymology/isolation &amp; purification/metabolism ; Bacterial Proteins/genetics ; Biosynthetic Pathways ; Feces/microbiology ; *Gastrointestinal Microbiome ; Humans ; Metagenomics/*methods ; Methylamines/*metabolism ; Multilocus Sequence Typing ; Phylogeny ; Sequence Analysis, DNA/methods ; }, abstract = {BACKGROUND: Trimethylamine (TMA), produced by the gut microbiota from dietary quaternary amines (mainly choline and carnitine), is associated with atherosclerosis and severe cardiovascular disease. Currently, little information on the composition of TMA producers in the gut is available due to their low abundance and the requirement of specific functional-based detection methods as many taxa show disparate abilities to produce that compound.<br><br>RESULTS: In order to examine the TMA-forming potential of microbial communities, we established databases for the key genes of the main TMA-synthesis pathways, encoding choline TMA-lyase (cutC) and carnitine oxygenase (cntA), using a multi-level screening approach on 67,134 genomes revealing 1107 and 6738 candidates to exhibit cutC and cntA, respectively. Gene-targeted assays enumerating the TMA-producing community by quantitative PCR and characterizing its composition via Illumina sequencing were developed and applied on human fecal samples (n&#x2009;=&#x2009;50) where all samples contained potential&#xa0;TMA producers (cutC was detected in all individuals, whereas only 26% harbored cntA) constituting, however, only a minor part of the total community (below 1% in most samples). Obtained cutC amplicons were associated with various taxa, in particular with Clostridium XIVa strains and Eubacterium sp. strain AB3007, though a bulk of sequences displayed low nucleotide identities to references (average 86%&#x2009;&#xb1;&#x2009;7%) indicating that key human TMA producers are yet to be isolated. Co-occurrence analysis revealed specific groups governing the community structure of cutC-exhibiting taxa across samples. CntA amplicons displayed high identities (~99%) to Gammaproteobacteria-derived references, primarily from Escherichia coli. Metagenomic analysis of samples provided by the Human Microbiome Project (n&#x2009;=&#x2009;154) confirmed the abundance patterns as well as overall taxonomic compositions obtained with our assays, though at much lower resolution, whereas 16S ribosomal RNA gene sequence analysis could not adequately uncover the TMA-producing potential.<br><br>CONCLUSIONS: In this study, we developed a diagnostic framework that enabled the quantification and comprehensive characterization of the TMA-producing potential in human fecal samples. The key players were identified, and together with predictions on their environmental niches using functional genomics on most closely related reference strains, we provide crucial information for the development of specific treatment strategies to restrain TMA producers and limit their proliferation.}, }
@article {pmid28480145, year = {2017}, author = {Santiago-Rodriguez, TM and Narganes-Storde, Y and Chanlatte-Baik, L and Toranzos, GA and Cano, RJ}, title = {Insights of the dental calculi microbiome of pre-Columbian inhabitants from Puerto Rico.}, journal = {PeerJ}, volume = {5}, number = {}, pages = {e3277}, pmid = {28480145}, issn = {2167-8359}, abstract = {BACKGROUND: The study of ancient microorganisms in mineralized dental plaque or calculi is providing insights into microbial evolution, as well as lifestyles and disease states of extinct cultures; yet, little is still known about the oral microbial community structure and function of pre-Columbian Caribbean cultures. In the present study, we investigated the dental calculi microbiome and predicted function of one of these cultures, known as the Saladoid. The Saladoids were horticulturalists that emphasized root-crop production. Fruits, as well as small marine and terrestrial animals were also part of the Saladoid diet.<br><br>METHODS: Dental calculi samples were recovered from the archaeological site of Sorc&#xe9;, in the municipal island of Vieques, Puerto Rico, characterized using 16S rRNA gene high-throughput sequencing, and compared to the microbiome of previously characterized coprolites of the same culture, as well modern plaque, saliva and stool microbiomes available from the Human Microbiome Project.<br><br>RESULTS: Actinobacteria, Proteobacteria and Firmicutes comprised the majority of the Saladoid dental calculi microbiome. The Saladoid dental calculi microbiome was distinct when compared to those of modern saliva and dental plaque, but showed the presence of common inhabitants of modern oral cavities including Streptococcus sp., Veillonella dispar and Rothia mucilaginosa. Cell motility, signal transduction and biosynthesis of other secondary metabolites may be unique features of the Saladoid microbiome.<br><br>DISCUSSION: Results suggest that the Saladoid dental calculi microbiome structure and function may possibly reflect a horticulturalist lifestyle and distinct dietary habits. Results also open the opportunity to further elucidate oral disease states in extinct Caribbean cultures and extinct indigenous cultures with similar lifestyles.}, }
@article {pmid28473000, year = {2017}, author = {Lee, STM and Kahn, SA and Delmont, TO and Shaiber, A and Esen, &#xd6;C and Hubert, NA and Morrison, HG and Antonopoulos, DA and Rubin, DT and Eren, AM}, title = {Tracking microbial colonization in fecal microbiota transplantation experiments via genome-resolved metagenomics.}, journal = {Microbiome}, volume = {5}, number = {1}, pages = {50}, pmid = {28473000}, issn = {2049-2618}, support = {P30 DK042086/DK/NIDDK NIH HHS/United States ; T32 EB009412/EB/NIBIB NIH HHS/United States ; }, mesh = {Adult ; Bacteria/classification/*growth &amp; development ; Clostridium Infections/microbiology/*therapy ; DNA, Bacterial/genetics ; Fecal Microbiota Transplantation/*methods ; Female ; Gastrointestinal Tract/*microbiology ; Humans ; Living Donors ; Male ; Metagenomics/*methods ; Phylogeny ; Sequence Analysis, DNA/methods ; Young Adult ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridium difficile infection and shows promise for treating other medical conditions associated with intestinal dysbioses. However, we lack a sufficient understanding of which microbial populations successfully colonize the recipient gut, and the widely used approaches to study the microbial ecology of FMT experiments fail to provide enough resolution to identify populations that are likely responsible for FMT-derived benefits.<br><br>METHODS: We used shotgun metagenomics together with assembly and binning strategies to reconstruct metagenome-assembled genomes (MAGs) from fecal samples of a single FMT donor. We then used metagenomic mapping to track the occurrence and distribution patterns of donor MAGs in two FMT recipients.<br><br>RESULTS: Our analyses revealed that 22% of the 92 highly complete bacterial MAGs that we identified from the donor successfully colonized and remained abundant in two recipients for at least 8&#xa0;weeks. Most MAGs with a high colonization rate belonged to the order Bacteroidales. The vast majority of those that lacked evidence of colonization belonged to the order Clostridiales, and colonization success was negatively correlated with the number of genes related to sporulation. Our analysis of 151 publicly available gut metagenomes showed that the donor MAGs that colonized both recipients were prevalent, and the ones that colonized neither were rare across the participants of the Human Microbiome Project. Although our dataset showed a link between taxonomy and the colonization ability of a given MAG, we also identified MAGs that belong to the same taxon with different colonization properties, highlighting the importance of an appropriate level of resolution to explore the functional basis of colonization and to identify targets for cultivation, hypothesis generation, and testing in model systems.<br><br>CONCLUSIONS: The analytical strategy adopted in our study can provide genomic insights into bacterial populations that may be critical to the efficacy of FMT due to their success in gut colonization and metabolic properties, and guide cultivation efforts to investigate mechanistic underpinnings of this procedure beyond associations.}, }
@article {pmid28462050, year = {2017}, author = {Walsh, CJ and Guinane, CM and O' Toole, PW and Cotter, PD}, title = {A Profile Hidden Markov Model to investigate the distribution and frequency of LanB-encoding lantibiotic modification genes in the human oral and gut microbiome.}, journal = {PeerJ}, volume = {5}, number = {}, pages = {e3254}, pmid = {28462050}, issn = {2167-8359}, abstract = {BACKGROUND: The human microbiota plays a key role in health and disease, and bacteriocins, which are small, bacterially produced, antimicrobial peptides, are likely to have an important function in the stability and dynamics of this community. Here we examined the density and distribution of the subclass I lantibiotic modification protein, LanB, in human oral and stool microbiome datasets using a specially constructed profile Hidden Markov Model (HMM).<br><br>METHODS: The model was validated by correctly identifying known lanB genes in the genomes of known bacteriocin producers more effectively than other methods, while being sensitive enough to differentiate between different subclasses of lantibiotic modification proteins. This approach was compared with two existing methods to screen both genomic and metagenomic datasets obtained from the Human Microbiome Project (HMP).<br><br>RESULTS: Of the methods evaluated, the new profile HMM identified the greatest number of putative LanB proteins in the stool and oral metagenome data while BlastP identified the fewest. In addition, the model identified more LanB proteins than a pre-existing Pfam lanthionine dehydratase model. Searching the gastrointestinal tract subset of the HMP reference genome database with the new HMM identified seven putative subclass I lantibiotic producers, including two members of the Coprobacillus genus.<br><br>CONCLUSIONS: These findings establish custom profile HMMs as a potentially powerful tool in the search for novel bioactive producers with the power to benefit human health, and reinforce the repertoire of apparent bacteriocin-encoding gene clusters that may have been overlooked by culture-dependent mining efforts to date.}, }
@article {pmid28448493, year = {2017}, author = {Fisher, CK and Mora, T and Walczak, AM}, title = {Variable habitat conditions drive species covariation in the human microbiota.}, journal = {PLoS computational biology}, volume = {13}, number = {4}, pages = {e1005435}, pmid = {28448493}, issn = {1553-7358}, mesh = {Computational Biology ; *Ecosystem ; Humans ; Microbiota/*genetics/*physiology ; Models, Biological ; Species Specificity ; }, abstract = {Two species with similar resource requirements respond in a characteristic way to variations in their habitat-their abundances rise and fall in concert. We use this idea to learn how bacterial populations in the microbiota respond to habitat conditions that vary from person-to-person across the human population. Our mathematical framework shows that habitat fluctuations are sufficient for explaining intra-bodysite correlations in relative species abundances from the Human Microbiome Project. We explicitly show that the relative abundances of closely related species are positively correlated and can be predicted from taxonomic relationships. We identify a small set of functional pathways related to metabolism and maintenance of the cell wall that form the basis of a common resource sharing niche space of the human microbiota.}, }
@article {pmid28437450, year = {2017}, author = {Cai, Y and Zheng, W and Yao, J and Yang, Y and Mai, V and Mao, Q and Sun, Y}, title = {ESPRIT-Forest: Parallel clustering of massive amplicon sequence data in subquadratic time.}, journal = {PLoS computational biology}, volume = {13}, number = {4}, pages = {e1005518}, pmid = {28437450}, issn = {1553-7358}, support = {R01 AI125982/AI/NIAID NIH HHS/United States ; }, mesh = {*Algorithms ; *Cluster Analysis ; Computational Biology ; Databases, Genetic ; Humans ; Microbiota/genetics ; RNA, Ribosomal, 16S/genetics ; Sequence Alignment/*methods ; Sequence Analysis, RNA/*methods ; }, abstract = {The rapid development of sequencing technology has led to an explosive accumulation of genomic sequence data. Clustering is often the first step to perform in sequence analysis, and hierarchical clustering is one of the most commonly used approaches for this purpose. However, it is currently computationally expensive to perform hierarchical clustering of extremely large sequence datasets due to its quadratic time and space complexities. In this paper we developed a new algorithm called ESPRIT-Forest for parallel hierarchical clustering of sequences. The algorithm achieves subquadratic time and space complexity and maintains a high clustering accuracy comparable to the standard method. The basic idea is to organize sequences into a pseudo-metric based partitioning tree for sub-linear time searching of nearest neighbors, and then use a new multiple-pair merging criterion to construct clusters in parallel using multiple threads. The new algorithm was tested on the human microbiome project (HMP) dataset, currently one of the largest published microbial 16S rRNA sequence dataset. Our experiment demonstrated that with the power of parallel computing it is now compu- tationally feasible to perform hierarchical clustering analysis of tens of millions of sequences. The software is available at http://www.acsu.buffalo.edu/∼yijunsun/lab/ESPRIT-Forest.html.}, }
@article {pmid28435844, year = {2016}, author = {Stanley, N and Shai, S and Taylor, D and Mucha, PJ}, title = {Clustering network layers with the strata multilayer stochastic block model.}, journal = {IEEE transactions on network science and engineering}, volume = {3}, number = {2}, pages = {95-105}, pmid = {28435844}, issn = {2327-4697}, support = {R01 HD075712/HD/NICHD NIH HHS/United States ; T32 CA201159/CA/NCI NIH HHS/United States ; T32 GM067553/GM/NIGMS NIH HHS/United States ; }, abstract = {Multilayer networks are a useful data structure for simultaneously capturing multiple types of relationships between a set of nodes. In such networks, each relational definition gives rise to a layer. While each layer provides its own set of information, community structure across layers can be collectively utilized to discover and quantify underlying relational patterns between nodes. To concisely extract information from a multilayer network, we propose to identify and combine sets of layers with meaningful similarities in community structure. In this paper, we describe the "strata multilayer stochastic block model" (sMLSBM), a probabilistic model for multilayer community structure. The central extension of the model is that there exist groups of layers, called "strata", which are defined such that all layers in a given stratum have community structure described by a common stochastic block model (SBM). That is, layers in a stratum exhibit similar node-to-community assignments and SBM probability parameters. Fitting the sMLSBM to a multilayer network provides a joint clustering that yields node-to-community and layer-to-stratum assignments, which cooperatively aid one another during inference. We describe an algorithm for separating layers into their appropriate strata and an inference technique for estimating the SBM parameters for each stratum. We demonstrate our method using synthetic networks and a multilayer network inferred from data collected in the Human Microbiome Project.}, }
@article {pmid28391505, year = {2017}, author = {Somboonna, N and Wilantho, A and Srisuttiyakorn, C and Assawamakin, A and Tongsima, S}, title = {Bacterial communities on facial skin of teenage and elderly Thai females.}, journal = {Archives of microbiology}, volume = {199}, number = {7}, pages = {1035-1042}, doi = {10.1007/s00203-017-1375-0}, pmid = {28391505}, issn = {1432-072X}, support = {RSA58-80061//Thailand Research Fund/ ; }, mesh = {Acne Vulgaris/*microbiology ; Adult ; *Bacteria/classification/genetics/isolation &amp; purification ; Base Sequence ; Female ; Humans ; Microbiota/*genetics ; Middle Aged ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; Skin/*microbiology ; Thailand ; Young Adult ; }, abstract = {The Human Microbiome Project was first established to understand the roles of human-associated microbes to human health and disease. This study presents preliminary findings of Thai female facial skin microbiome using three pooled samples from groups of skin microbiome profiles, namely (1) healthy and (2) acne-prone young adults (teenage.hea and teenage.acn) and (3) healthy elderly adults (elderly.hea) based on standard dermatological criteria. These samples were sequenced using 454-pyrosequencing targeting 16S rRNA (V3-V4 regions). Good's coverage index of greater than 92% shows sufficient sampling of our data for each group. Three unique OTUs for each microbiome profile (43, 258 and 59 for teenage.hea, teenage.acn and ederly.hea, respectively) were obtained with 134 shared OTUs among the three datasets. Based on Morisita-Horn similarity coefficient, age is the major factor that brings the community relationship factor closer. The comparison among the three datasets reveal majority of Gemmatimonadetes, Planctomycetes and Nitrospirae in the teenage.hea, whereas Firmicutes are more prevalent in teenage.acn and elderly.hea skin types. In addition, when comparing Thai facial microbial diversity with the 16S data from U.S. forehead female database, significant differences were found among orders of bacteria, pointing to possible differences in human ecto-flora.}, }
@article {pmid28383789, year = {2017}, author = {Acharya, A and Chan, Y and Kheur, S and Kheur, M and Gopalakrishnan, D and Watt, RM and Mattheos, N}, title = {Salivary microbiome of an urban Indian cohort and patterns linked to subclinical inflammation.}, journal = {Oral diseases}, volume = {23}, number = {7}, pages = {926-940}, doi = {10.1111/odi.12676}, pmid = {28383789}, issn = {1601-0825}, mesh = {Adult ; Aged ; *Asymptomatic Diseases ; Female ; Humans ; India ; Inflammation/*microbiology ; Interleukin-1beta/metabolism ; Male ; *Microbiota ; Middle Aged ; Saliva/metabolism/*microbiology ; Urban Population ; }, abstract = {OBJECTIVE: To profile salivary microbiomes of an urban-living, healthy Indian cohort and explore associations with proinflammatory status.<br><br>METHODS: Fifty-one clinically healthy Indian subjects' salivary microbiomes were analyzed using 16S rRNA Illumina MiSeq sequencing. Community distribution was compared with salivary data from the Human Microbiome Project (HMP). Indian subjects were clustered using microbiome-based "partitioning along medoids" (PAM), and relationships of interleukin-1 beta levels with community composition were analyzed.<br><br>RESULTS: Indian subjects presented higher phylogenetic diversity than HMP. Several taxa associated with traditional societies gut microbiomes (Bacteroidales, Paraprevotellaceae, and Spirochaetaceae) were raised. Bifidobacteriaceae and Lactobacillaceae were approximately fourfold greater. A PAM cluster enriched in several Proteobacteria, Actinobacteria, and Bacilli taxa and having almost twofold higher Prevotella to Bacteroides ratio showed significant overrepresentation of subjects within the highest quartile of salivary interleukin-1 beta levels. Abiotrophia, Anaerobacillus, Micrococcus, Aggregatibacter, Halomonas, Propionivivrio, Paracoccus, Mannhemia, unclassified Bradyrhizobiaceae, and Caulobacteraceae were each significant indicators of presence in the highest interleukin-1 beta quartile. 2 OTUs representing Lactobacillus fermentum and Cardiobacterium hominis significantly correlated with interleukin-1 beta levels.<br><br>CONCLUSION: The salivary microbiome of this urban-dwelling Indian cohort differed significantly from that of a well-studied Western cohort. Specific community patterns were putatively associated with subclinical inflammation levels.}, }
@article {pmid28375407, year = {2017}, author = {Lacy, BE}, title = {Hot Topics in Primary Care: Role of the Microbiome in Disease: Implications for Treatment of Irritable Bowel Syndrome.}, journal = {The Journal of family practice}, volume = {66}, number = {4 Suppl}, pages = {S40-S45}, pmid = {28375407}, issn = {1533-7294}, mesh = {Anti-Bacterial Agents/*therapeutic use ; Education, Medical, Continuing ; Gastrointestinal Microbiome/*drug effects ; Humans ; Irritable Bowel Syndrome/*diagnosis/*drug therapy/microbiology/physiopathology ; *Practice Guidelines as Topic ; Primary Health Care/*standards ; Probiotics/*therapeutic use ; United States ; }, abstract = {Dietary and some other treatments for IBS are supported by a growing body of evidence, much of which comes from programs such as the Human Microbiome Project and Human Gut Microbiome Initiative, which were intended to identify and characterize microorganisms found in association with both healthy and diseased humans. These programs used state-of-the-art technology to characterize the human microbiome from multiple body sites. This evidence indicates that the gut microbiome plays an important role in IBS and some other gastrointestinal (GI) disorders.}, }
@article {pmid28357466, year = {2017}, author = {Steinhagen, PR and Baumgart, DC}, title = {[Fundamentals of the microbiome].}, journal = {Der Internist}, volume = {58}, number = {5}, pages = {429-434}, pmid = {28357466}, issn = {1432-1289}, mesh = {Disease ; Humans ; *Microbial Consortia ; }, abstract = {Until the middle of the 20th century, clinical microbiology was limited to bacterial cultures enabling the detection of pathogenic microorganisms. Knowledge about the mutual relationship between humans and microorganisms has increased slowly. With the introduction of culture-independent analysis methods, comprehensive cataloging of the human microbiome was possible for the first time. Since then, compositional changes in relation to diseases have been studied. The goals of the Human Microbiome Project and MetaHIT include comparative studies of healthy and diseased individuals. Numerous libraries on time- and location-dependent changes of the microbiota composition in human diseases have been created. However, a mathematical correlation does not equal biological or medical relevance. Future research needs to validate the hypotheses generated in these studies in functional experiments and evaluate their true impact on clinical practice.}, }
@article {pmid28337070, year = {2017}, author = {Tighe, S and Afshinnekoo, E and Rock, TM and McGrath, K and Alexander, N and McIntyre, A and Ahsanuddin, S and Bezdan, D and Green, SJ and Joye, S and Stewart Johnson, S and Baldwin, DA and Bivens, N and Ajami, N and Carmical, JR and Herriott, IC and Colwell, R and Donia, M and Foox, J and Greenfield, N and Hunter, T and Hoffman, J and Hyman, J and Jorgensen, E and Krawczyk, D and Lee, J and Levy, S and Garcia-Reyero, N and Settles, M and Thomas, K and Gómez, F and Schriml, L and Kyrpides, N and Zaikova, E and Penterman, J and Mason, CE}, title = {Genomic Methods and Microbiological Technologies for Profiling Novel and Extreme Environments for the Extreme Microbiome Project (XMP).}, journal = {Journal of biomolecular techniques : JBT}, volume = {28}, number = {1}, pages = {31-39}, pmid = {28337070}, issn = {1943-4731}, support = {R01 AI125416/AI/NIAID NIH HHS/United States ; R01 ES021006/ES/NIEHS NIH HHS/United States ; R01 NS076465/NS/NINDS NIH HHS/United States ; R25 EB020393/EB/NIBIB NIH HHS/United States ; }, mesh = {DNA, Bacterial/genetics/isolation &amp; purification ; *Environmental Microbiology ; Extreme Environments ; Metagenome ; Microbiota/*genetics ; Molecular Typing/standards ; RNA, Bacterial/genetics/isolation &amp; purification ; Reference Standards ; Sequence Analysis, DNA/standards ; }, abstract = {The Extreme Microbiome Project (XMP) is a project launched by the Association of Biomolecular Resource Facilities Metagenomics Research Group (ABRF MGRG) that focuses on whole genome shotgun sequencing of extreme and unique environments using a wide variety of biomolecular techniques. The goals are multifaceted, including development and refinement of new techniques for the following: 1) the detection and characterization of novel microbes, 2) the evaluation of nucleic acid techniques for extremophilic samples, and 3) the identification and implementation of the appropriate bioinformatics pipelines. Here, we highlight the different ongoing projects that we have been working on, as well as details on the various methods we use to characterize the microbiome and metagenome of these complex samples. In particular, we present data of a novel multienzyme extraction protocol that we developed, called Polyzyme or MetaPolyZyme. Presently, the XMP is characterizing sample sites around the world with the intent of discovering new species, genes, and gene clusters. Once a project site is complete, the resulting data will be publically available. Sites include Lake Hillier in Western Australia, the "Door to Hell" crater in Turkmenistan, deep ocean brine lakes of the Gulf of Mexico, deep ocean sediments from Greenland, permafrost tunnels in Alaska, ancient microbial biofilms from Antarctica, Blue Lagoon Iceland, Ethiopian toxic hot springs, and the acidic hypersaline ponds in Western Australia.}, }
@article {pmid28216014, year = {2017}, author = {Bhattacharyya, M and Ghosh, T and Shankar, S and Tomar, N}, title = {The conserved phylogeny of blood microbiome.}, journal = {Molecular phylogenetics and evolution}, volume = {109}, number = {}, pages = {404-408}, doi = {10.1016/j.ympev.2017.02.001}, pmid = {28216014}, issn = {1095-9513}, mesh = {Archaea/classification ; Bacteria/*classification ; Bacterial Proteins/genetics ; *Biological Evolution ; Blood/*microbiology ; Fungal Proteins/genetics ; Humans ; *Microbiota ; Phylogeny ; }, abstract = {The proliferation and intensification of diseases have forced every researcher to take actions for a robust understanding of the organisms. This demands deep knowledge about the cells and tissues in an organ and its entire surroundings, more precisely the microbiome community which involves viruses, bacteria, archaea, among others. They play an important role in the function of our body, and act both as a deterrent as well as shelter for diseases. Therefore, it is pertinent to study the relation within the microbiome in a human body. In this work, we analyze the sequence data provided through the Human Microbiome Project to explore evolutionary relations within blood microbiome. The objective is to analyze the common proteins present in the different microbes in the blood and find their phylogeny. The analysis of the phylogenetic relation between these species provides important insights about the conservedness of phylogeny of blood microbiome. Interestingly, the co-existence of five of those common proteins is observed in human too.}, }
@article {pmid28178947, year = {2017}, author = {Wadsworth, WD and Argiento, R and Guindani, M and Galloway-Pena, J and Shelburne, SA and Vannucci, M}, title = {An integrative Bayesian Dirichlet-multinomial regression model for the analysis of taxonomic abundances in microbiome data.}, journal = {BMC bioinformatics}, volume = {18}, number = {1}, pages = {94}, pmid = {28178947}, issn = {1471-2105}, support = {L30 CA209245/CA/NCI NIH HHS/United States ; P30 CA016672/CA/NCI NIH HHS/United States ; T32 CA096520/CA/NCI NIH HHS/United States ; }, mesh = {Algorithms ; Bacteria/*classification ; Bayes Theorem ; Computer Simulation ; Humans ; *Linear Models ; Markov Chains ; *Microbiota ; Monte Carlo Method ; }, abstract = {BACKGROUND: The Human Microbiome has been variously associated with the immune-regulatory mechanisms involved in the prevention or development of many non-infectious human diseases such as autoimmunity, allergy and cancer. Integrative approaches which aim at associating the composition of the human microbiome with other available information, such as clinical covariates and environmental predictors, are paramount to develop a more complete understanding of the role of microbiome in disease development.<br><br>RESULTS: In this manuscript, we propose a Bayesian Dirichlet-Multinomial regression model which uses spike-and-slab priors for the selection of significant associations between a set of available covariates and taxa from a microbiome abundance table. The approach allows straightforward incorporation of the covariates through a log-linear regression parametrization of the parameters of the Dirichlet-Multinomial likelihood. Inference is conducted through a Markov Chain Monte Carlo algorithm, and selection of the significant covariates is based upon the assessment of posterior probabilities of inclusions and the thresholding of the Bayesian false discovery rate. We design a simulation study to evaluate the performance of the proposed method, and then apply our model on a publicly available dataset obtained from the Human Microbiome Project which associates taxa abundances with KEGG orthology pathways. The method is implemented in specifically developed R code, which has been made publicly available.<br><br>CONCLUSIONS: Our method compares favorably in simulations to several recently proposed approaches for similarly structured data, in terms of increased accuracy and reduced false positive as well as false negative rates. In the application to the data from the Human Microbiome Project, a close evaluation of the biological significance of our findings confirms existing associations in the literature.}, }
@article {pmid28146577, year = {2017}, author = {Traykova, D and Schneider, B and Chojkier, M and Buck, M}, title = {Blood Microbiome Quantity and the Hyperdynamic Circulation in Decompensated Cirrhotic Patients.}, journal = {PloS one}, volume = {12}, number = {2}, pages = {e0169310}, pmid = {28146577}, issn = {1932-6203}, support = {R01 DK084139/DK/NIDDK NIH HHS/United States ; R41 HL122022/HL/NHLBI NIH HHS/United States ; R41 HL127919/HL/NHLBI NIH HHS/United States ; RC1 DK087031/DK/NIDDK NIH HHS/United States ; }, mesh = {Aged ; Bacteria/classification/genetics ; Biomarkers ; Case-Control Studies ; Cytokines/genetics/metabolism ; Gastrointestinal Microbiome ; Gene Expression Regulation ; *Hemodynamics ; Humans ; Liver Cirrhosis/*complications/diagnosis/etiology/*physiopathology ; Liver Function Tests ; Macrophages/immunology/metabolism ; Male ; Metagenome ; Metagenomics/methods ; *Microbiota ; Middle Aged ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; Nitric Oxide/metabolism ; Sepsis/*etiology ; }, abstract = {BACKGROUND: Recently, a complex microbiome was comprehensibly characterized in the serum and ascitic fluid of cirrhotic patients. In the current study, we investigated for the first time the induction of inflammatory pathways and Nitric Oxide, as well as the systemic hemodynamics in conjunction with the blood microbiome in a Child-Pugh class B cirrhotic cohort.<br><br>METHODS AND FINDINGS: We used the Intestinal Infections Microbial DNA qPCR Array to screen for 53 bacterial DNA from the gut in the blood. Assays were designed using the 16S rRNA gene as a target, and PCR amplification primers (based on the Human Microbiome Project) and hydrolysis-probe detection. Eighteen systemic hemodynamic parameters were measured non-invasively by impedance cardiography using the BioZ ICG monitor. The inflammatory response was assessed by measuring blood cytokines, Nitric Oxide RNA arrays, and Nitric Oxide. In the blood of this cirrhotic cohort, we detected 19 of 53 bacterial species tested. The number of bacterial species was markedly increased in the blood of cirrhotic patients compared to control individuals (0.2+/-0.4 vs 3.1+/-2.3; 95% CI: 1.3 to 4.9; P = 0.0030). The total bacterial DNA was also increased in the blood of cirrhotic subjects compared to control subjects (0.2+/- 1.1 vs 41.8+/-132.1; 95% CI: 6.0 to 77.2; P = 0.0022). In the cirrhotic cohort, the Cardiac Output increased by 37% and the Systemic Vascular Resistance decreased by 40% (P< 0.00001 for both compared to control subjects). Systemic Vascular Resistance was inversely correlated to blood bacterial DNA quantity (- 0.621; 95% CI -0.843 to -0.218; P = 0.0060), blood bacterial species number (- 0.593; 95% CI -0.83 to -0.175; P = 0.0095; logistic regression: Chi Square = 5.8877; P = 0.0152), and serum Nitric Oxide (- 0.705; 95% CI -0.881 to -0.355; P = 0.0011). Many members of the Nitric Oxide signaling pathway gene family were increased in cirrhotic subjects.<br><br>CONCLUSIONS: Our study identified blood bacterial DNA in ~ 90% of the cirrhotic patients without clinical evidences of infection, and suggests that the quantity of bacterial DNA in blood may stimulate signaling pathways, including Nitric Oxide, that could decrease systemic vascular resistance and increase cardiac output.}, }
@article {pmid28111075, year = {2017}, author = {Guo, CJ and Chang, FY and Wyche, TP and Backus, KM and Acker, TM and Funabashi, M and Taketani, M and Donia, MS and Nayfach, S and Pollard, KS and Craik, CS and Cravatt, BF and Clardy, J and Voigt, CA and Fischbach, MA}, title = {Discovery of Reactive Microbiota-Derived Metabolites that Inhibit Host Proteases.}, journal = {Cell}, volume = {168}, number = {3}, pages = {517-526.e18}, pmid = {28111075}, issn = {1097-4172}, support = {R01 GM104659/GM/NIGMS NIH HHS/United States ; R37 CA087660/CA/NCI NIH HHS/United States ; R01 DK101674/DK/NIDDK NIH HHS/United States ; R01 AT009874/AT/NCCIH NIH HHS/United States ; T32 GM067547/GM/NIGMS NIH HHS/United States ; F32 GM111012/GM/NIGMS NIH HHS/United States ; R01 DK110174/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Bacillus subtilis/genetics ; Bacteria/classification/genetics/*metabolism ; Escherichia coli/genetics ; Feces/microbiology ; *Gastrointestinal Microbiome ; Humans ; *Microbiota ; Peptide Synthases/genetics/*metabolism ; Phylogeny ; Pyrazines/*metabolism ; }, abstract = {The gut microbiota modulate host biology in numerous ways, but little is known about the molecular mediators of these interactions. Previously, we found a widely distributed family of nonribosomal peptide synthetase gene clusters in gut bacteria. Here, by expressing a subset of these clusters in Escherichia coli or Bacillus subtilis, we show that they encode pyrazinones and dihydropyrazinones. At least one of the 47 clusters is present in 88% of the National Institutes of Health Human Microbiome Project (NIH HMP) stool samples, and they are transcribed under conditions of host colonization. We present evidence that the active form of these molecules is the initially released peptide aldehyde, which bears potent protease inhibitory activity and selectively targets a subset of cathepsins in human cell proteomes. Our findings show that an approach combining bioinformatics, synthetic biology, and heterologous gene cluster expression can rapidly expand our knowledge of the metabolic potential of the microbiota while avoiding the challenges of cultivating fastidious commensals.}, }
@article {pmid28028549, year = {2016}, author = {Lynch, MD and Neufeld, JD}, title = {SSUnique: Detecting Sequence Novelty in Microbiome Surveys.}, journal = {mSystems}, volume = {1}, number = {6}, pages = {}, pmid = {28028549}, issn = {2379-5077}, abstract = {High-throughput sequencing of small-subunit (SSU) rRNA genes has revolutionized understanding of microbial communities and facilitated investigations into ecological dynamics at unprecedented scales. Such extensive SSU rRNA gene sequence libraries, constructed from DNA extracts of environmental or host-associated samples, often contain a substantial proportion of unclassified sequences, many representing organisms with novel taxonomy (taxonomic "blind spots") and potentially unique ecology. Indeed, these novel taxonomic lineages are associated with so-called microbial "dark matter," which is the genomic potential of these lineages. Unfortunately, characterization beyond "unclassified" is challenging due to relatively short read lengths and large data set sizes. Here we demonstrate how mining of phylogenetically novel sequences from microbial ecosystems can be automated using SSUnique, a software pipeline that filters unclassified and/or rare operational taxonomic units (OTUs) from 16S rRNA gene sequence libraries by screening against consensus structural models for SSU rRNA. Phylogenetic position is inferred against a reference data set, and additional characterization of novel clades is also included, such as targeted probe/primer design and mining of assembled metagenomes for genomic context. We show how SSUnique reproduced a previous analysis of phylogenetic novelty from an Arctic tundra soil and demonstrate the recovery of highly novel clades from data sets associated with both the Earth Microbiome Project (EMP) and Human Microbiome Project (HMP). We anticipate that SSUnique will add to the expanding computational toolbox supporting high-throughput sequencing approaches for the study of microbial ecology and phylogeny. IMPORTANCE Extensive SSU rRNA gene sequence libraries, constructed from DNA extracts of environmental or host-associated samples, often contain many unclassified sequences, many representing organisms with novel taxonomy (taxonomic "blind spots") and potentially unique ecology. This novelty is poorly explored in standard workflows, which narrows the breadth and discovery potential of such studies. Here we present the SSUnique analysis pipeline, which will promote the exploration of unclassified diversity in microbiome research and, importantly, enable the discovery of substantial novel taxonomic lineages through the analysis of a large variety of existing data sets.}, }
@article {pmid27997751, year = {2017}, author = {Jackrel, SL and Owens, SM and Gilbert, JA and Pfister, CA}, title = {Identifying the plant-associated microbiome across aquatic and terrestrial environments: the effects of amplification method on taxa discovery.}, journal = {Molecular ecology resources}, volume = {17}, number = {5}, pages = {931-942}, doi = {10.1111/1755-0998.12645}, pmid = {27997751}, issn = {1755-0998}, mesh = {Bacteria/*classification/*genetics ; DNA, Bacterial/chemistry/genetics ; DNA, Ribosomal/chemistry/genetics ; Metagenomics/*methods ; *Microbiota ; Plants/*microbiology ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; }, abstract = {Plants in terrestrial and aquatic environments contain a diverse microbiome. Yet, the chloroplast and mitochondria organelles of the plant eukaryotic cell originate from free-living cyanobacteria and Rickettsiales. This represents a challenge for sequencing the plant microbiome with universal primers, as ~99% of 16S rRNA sequences may consist of chloroplast and mitochondrial sequences. Peptide nucleic acid clamps offer a potential solution by blocking amplification of host-associated sequences. We assessed the efficacy of chloroplast and mitochondria-blocking clamps against a range of microbial taxa from soil, freshwater and marine environments. While we found that the mitochondrial blocking clamps appear to be a robust method for assessing animal-associated microbiota, Proteobacterial 16S rRNA binds to the chloroplast-blocking clamp, resulting in a strong sequencing bias against this group. We attribute this bias to a conserved 14-bp sequence in the Proteobacteria that matches the 17-bp chloroplast-blocking clamp sequence. By scanning the Greengenes database, we provide a reference list of nearly 1500 taxa that contain this 14-bp sequence, including 48 families such as the Rhodobacteraceae, Phyllobacteriaceae, Rhizobiaceae, Kiloniellaceae and Caulobacteraceae. To determine where these taxa are found in nature, we mapped this taxa reference list against the Earth Microbiome Project database. These taxa are abundant in a variety of environments, particularly aquatic and semiaquatic freshwater and marine habitats. To facilitate informed decisions on effective use of organelle-blocking clamps, we provide a searchable database of microbial taxa in the Greengenes and Silva databases matching various n-mer oligonucleotides of each PNA sequence.}, }
@article {pmid27913230, year = {2017}, author = {Brooks, JP and Edwards, DJ and Blithe, DL and Fettweis, JM and Serrano, MG and Sheth, NU and Strauss, JF and Buck, GA and Jefferson, KK}, title = {Effects of combined oral contraceptives, depot medroxyprogesterone acetate and the levonorgestrel-releasing intrauterine system on the vaginal microbiome.}, journal = {Contraception}, volume = {95}, number = {4}, pages = {405-413}, pmid = {27913230}, issn = {1879-0518}, support = {P60 MD002256/MD/NIMHD NIH HHS/United States ; U54 DE023786/DE/NIDCR NIH HHS/United States ; UH3 AI083263/AI/NIAID NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Condoms ; Contraception/*methods ; Contraceptives, Oral, Combined/*pharmacology ; Female ; Humans ; Intrauterine Devices ; Levonorgestrel/*pharmacology ; Medroxyprogesterone Acetate/*pharmacology ; Microbiota/*drug effects ; Polymerase Chain Reaction ; RNA, Ribosomal, 16S ; Retrospective Studies ; Sexually Transmitted Diseases, Bacterial/prevention &amp; control ; Vagina/*drug effects ; Vaginosis, Bacterial/prevention &amp; control ; Young Adult ; }, abstract = {OBJECTIVES: Prior studies suggest that the composition of the vaginal microbiome may positively or negatively affect susceptibility to sexually transmitted infections (STIs) and bacterial vaginosis (BV). Some female hormonal contraceptive methods also appear to positively or negatively influence STI transmission and BV. Therefore, changes in the vaginal microbiome that are associated with different contraceptive methods may explain, in part, effects on STI transmission and BV.<br><br>STUDY DESIGN: We performed a retrospective study of 16S rRNA gene survey data of vaginal samples from a subset of participants from the Human Vaginal Microbiome Project at Virginia Commonwealth University. The subset included 682 women who reported using a single form of birth control that was condoms, combined oral contraceptives (COCs), depot medroxyprogesterone acetate (DMPA) or the levonorgestrel-releasing intrauterine system (LNG-IUS).<br><br>RESULTS: Women using COCs [adjusted odds ratio (aOR) 0.29, 95% confidence interval (CI) 0.13-0.64] and DMPA (aOR 0.34, 95% CI 0.13-0.89), but not LNG-IUS (aOR 1.55, 95% CI 0.72-3.35), were less likely to be colonized by BV-associated bacteria relative to women who used condoms. Women using COCs (aOR 1.94, 95% CI 1.25-3.02) were more likely to be colonized by beneficial H2O2-producing Lactobacillus species compared with women using condoms, while women using DMPA (aOR 1.09, 95% CI 0.63-1.86) and LNG-IUS (aOR 0.74, 95% CI 0.48-1.15) were not.<br><br>CONCLUSIONS: Use of COCs is significantly associated with increased vaginal colonization by healthy lactobacilli and reduced BV-associated taxa.<br><br>IMPLICATIONS: COC use may positively influence gynecologic health through an increase in healthy lactobacilli and a decrease in BV-associated bacterial taxa.}, }
@article {pmid27856569, year = {2016}, author = {Hartman, MR and Harrington, KT and Etson, CM and Fierman, MB and Slonim, DK and Walt, DR}, title = {Personal microbiomes and next-generation sequencing for laboratory-based education.}, journal = {FEMS microbiology letters}, volume = {363}, number = {23}, pages = {}, pmid = {27856569}, issn = {1574-6968}, support = {K12 GM074869/GM/NIGMS NIH HHS/United States ; R25 OD010547/OD/NIH HHS/United States ; }, mesh = {Computational Biology/*education ; *Curriculum ; High-Throughput Nucleotide Sequencing/*methods ; Humans ; Microbiota/*genetics ; Schools ; Students ; }, abstract = {Sequencing and bioinformatics technologies have advanced rapidly in recent years, driven largely by developments in next-generation sequencing (NGS) technology. Given the increasing importance of these advances, there is a growing need to incorporate concepts and practices relating to NGS into undergraduate and high school science curricula. We believe that direct access to sequencing and bioinformatics will improve the ability of students to understand the information obtained through these increasingly ubiquitous research tools. In this commentary, we discuss approaches and challenges for bringing NGS into the classroom based on our experiences in developing and running a microbiome project in high school and undergraduate courses. We describe strategies for maximizing student engagement through establishing personal relevance and utilizing an inquiry-based structure. Additionally, we address the practical issues of incorporating cutting edge technologies into an established curriculum. Looking forward, we anticipate that NGS educational experiments will become more commonplace as sequencing costs continue to decrease and the workflow becomes more user friendly.}, }
@article {pmid27822515, year = {2016}, author = {Kopylova, E and Navas-Molina, JA and Mercier, C and Xu, ZZ and Mahé, F and He, Y and Zhou, HW and Rognes, T and Caporaso, JG and Knight, R}, title = {Open-Source Sequence Clustering Methods Improve the State Of the Art.}, journal = {mSystems}, volume = {1}, number = {1}, pages = {}, pmid = {27822515}, issn = {2379-5077}, abstract = {Sequence clustering is a common early step in amplicon-based microbial community analysis, when raw sequencing reads are clustered into operational taxonomic units (OTUs) to reduce the run time of subsequent analysis steps. Here, we evaluated the performance of recently released state-of-the-art open-source clustering software products, namely, OTUCLUST, Swarm, SUMACLUST, and SortMeRNA, against current principal options (UCLUST and USEARCH) in QIIME, hierarchical clustering methods in mothur, and USEARCH's most recent clustering algorithm, UPARSE. All the latest open-source tools showed promising results, reporting up to 60% fewer spurious OTUs than UCLUST, indicating that the underlying clustering algorithm can vastly reduce the number of these derived OTUs. Furthermore, we observed that stringent quality filtering, such as is done in UPARSE, can cause a significant underestimation of species abundance and diversity, leading to incorrect biological results. Swarm, SUMACLUST, and SortMeRNA have been included in the QIIME 1.9.0 release. IMPORTANCE Massive collections of next-generation sequencing data call for fast, accurate, and easily accessible bioinformatics algorithms to perform sequence clustering. A comprehensive benchmark is presented, including open-source tools and the popular USEARCH suite. Simulated, mock, and environmental communities were used to analyze sensitivity, selectivity, species diversity (alpha and beta), and taxonomic composition. The results demonstrate that recent clustering algorithms can significantly improve accuracy and preserve estimated diversity without the application of aggressive filtering. Moreover, these tools are all open source, apply multiple levels of multithreading, and scale to the demands of modern next-generation sequencing data, which is essential for the analysis of massive multidisciplinary studies such as the Earth Microbiome Project (EMP) (J. A. Gilbert, J. K. Jansson, and R. Knight, BMC Biol 12:69, 2014, http://dx.doi.org/10.1186/s12915-014-0069-1).}, }
@article {pmid27612939, year = {2016}, author = {Nelson, DB and Rockwell, LC and Prioleau, MD and Goetzl, L}, title = {The role of the bacterial microbiota on reproductive and pregnancy health.}, journal = {Anaerobe}, volume = {42}, number = {}, pages = {67-73}, doi = {10.1016/j.anaerobe.2016.09.001}, pmid = {27612939}, issn = {1095-8274}, mesh = {Actinobacteria/growth &amp; development/pathogenicity ; Female ; Humans ; Lactobacillus/*physiology ; Leptotrichia/growth &amp; development/pathogenicity ; Male ; Microbiota/physiology ; Pregnancy ; Pregnancy Complications, Infectious/*microbiology/pathology/prevention &amp; control ; Reproduction/*physiology ; Sexual Behavior/physiology ; Sexual Partners ; Urethritis/*microbiology/pathology/prevention &amp; control ; Vagina/*microbiology ; Vaginosis, Bacterial/*microbiology/pathology/prevention &amp; control ; }, abstract = {Recent assessments have examined the composition of bacterial communities influencing reproductive, pregnancy and infant health. The Microbiome Project has made great strides in sequencing the microbiome and identifying the vast communities of microorganisms that inhabit our bodies and much work continues to examine the individual contribution of bacteria on health and disease to inform future therapies. This review explores the current literature outlining the contribution of important bacteria on reproductive health among sexually active men and women, outlines gaps in current research to determine causal and interventional relationships, and suggests future research initiatives. Novel treatments options to reduce adverse outcomes must recognize the heterogeneity of the bacteria within the microbiome and adequately assess long-term benefits in reducing disease burden and re-establishing a healthy Lactobacillus-dominant state. Recognizing other reservoirs outside of the lower genital track and within sexual partners as well as genetic and individual moderators may be most important for long-term cure and reduction of disease. It will be important to develop useful screening tools and comprehensively examine novel therapeutic options to promote the long-term reduction of high-risk bacteria and the re-establishment of healthy bacterial levels to considerably improve outcomes among pregnant women and sexually active men and women.}, }
@article {pmid27781166, year = {2016}, author = {Joseph, SJ and Li, B and Petit Iii, RA and Qin, ZS and Darrow, L and Read, TD}, title = {The single-species metagenome: subtyping Staphylococcus aureus core genome sequences from shotgun metagenomic data.}, journal = {PeerJ}, volume = {4}, number = {}, pages = {e2571}, pmid = {27781166}, issn = {2167-8359}, support = {R21 AI121860/AI/NIAID NIH HHS/United States ; }, abstract = {In this study we developed a genome-based method for detecting Staphylococcus aureus subtypes from metagenome shotgun sequence data. We used a binomial mixture model and the coverage counts at >100,000 known S. aureus SNP (single nucleotide polymorphism) sites derived from prior comparative genomic analysis to estimate the proportion of 40 subtypes in metagenome samples. We were able to obtain >87% sensitivity and >94% specificity at 0.025X coverage for S. aureus. We found that 321 and 149 metagenome samples from the Human Microbiome Project and metaSUB analysis of the New York City subway, respectively, contained S. aureus at genome coverage >0.025. In both projects, CC8 and CC30 were the most common S. aureus clonal complexes encountered. We found evidence that the subtype composition at different body sites of the same individual were more similar than random sampling and more limited evidence that certain body sites were enriched for particular subtypes. One surprising finding was the apparent high frequency of CC398, a lineage often associated with livestock, in samples from the tongue dorsum. Epidemiologic analysis of the HMP subject population suggested that high BMI (body mass index) and health insurance are possibly associated with S. aureus carriage but there was limited power to identify factors linked to carriage of even the most common subtype. In the NYC subway data, we found a small signal of geographic distance affecting subtype clustering but other unknown factors influence taxonomic distribution of the species around the city.}, }
@article {pmid27770008, year = {2017}, author = {Yu, G and Phillips, S and Gail, MH and Goedert, JJ and Humphrys, M and Ravel, J and Ren, Y and Caporaso, NE}, title = {Evaluation of Buccal Cell Samples for Studies of Oral Microbiota.}, journal = {Cancer epidemiology, biomarkers &amp; prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology}, volume = {26}, number = {2}, pages = {249-253}, doi = {10.1158/1055-9965.EPI-16-0538}, pmid = {27770008}, issn = {1538-7755}, mesh = {Adult ; Aged ; Feasibility Studies ; Female ; Follow-Up Studies ; Healthy Volunteers ; Humans ; Male ; Microbiota/*genetics ; Middle Aged ; Mouth Diseases/diagnosis/genetics/microbiology ; Mouth Mucosa/cytology/*microbiology ; Prospective Studies ; RNA, Bacterial/*analysis ; RNA, Ribosomal, 16S/analysis/*genetics ; }, abstract = {BACKGROUND: The human microbiota is postulated to affect cancer risk, but collecting microbiota specimens with prospective follow-up for diseases will take time. Buccal cell samples have been obtained from mouthwash for the study of human genomic DNA in many cohort studies. Here, we evaluate the feasibility of using buccal cell samples to examine associations of human microbiota and disease risk.<br><br>METHODS: We obtained buccal cells from mouthwash in 41 healthy participants using a protocol that is widely employed to obtain buccal cells for the study of human DNA. We compared oral microbiota from buccal cells with that from eight other oral sample types collected by following the protocols of the Human Microbiome Project. Microbiota profiles were determined by sequencing 16S rRNA gene V3-V4 region.<br><br>RESULTS: Compared with each of the eight other oral samples, the buccal cell samples had significantly more observed species (P < 0.002) and higher alpha diversity (Shannon index, P < 0.02). The microbial communities were more similar (smaller beta diversity) among buccal cells samples than in the other samples (P < 0.001 for 12 of 16 weighted and unweighted UniFrac distance comparisons). Buccal cell microbial profiles closely resembled saliva but were distinct from dental plaque and tongue dorsum.<br><br>CONCLUSIONS: Stored buccal cell samples in prospective cohort studies are a promising resource to study associations of oral microbiota with disease.<br><br>IMPACT: The feasibility of using existing buccal cell collections in large prospective cohorts allows investigations of the role of oral microbiota in chronic disease etiology in large population studies possible today. Cancer Epidemiol Biomarkers Prev; 26(2); 249-53. &#xa9;2016 AACR.}, }
@article {pmid27734124, year = {2017}, author = {Tu, Q and Li, J and Shi, Z and Chen, Y and Lin, L and Li, J and Wang, H and Yan, J and Zhou, Q and Li, X and Li, L and Zhou, J and He, Z}, title = {HuMiChip2 for strain level identification and functional profiling of human microbiomes.}, journal = {Applied microbiology and biotechnology}, volume = {101}, number = {1}, pages = {423-435}, doi = {10.1007/s00253-016-7910-0}, pmid = {27734124}, issn = {1432-0614}, mesh = {Humans ; Liver Cirrhosis ; Metagenomics/*methods ; Microarray Analysis/*methods ; Microbiological Techniques/*methods ; *Microbiota ; Nucleic Acid Hybridization/*methods ; Sensitivity and Specificity ; }, abstract = {With the massive data generated by the Human Microbiome Project, how to transform such data into useful information and knowledge remains challenging. Here, with currently available sequencing information (reference genomes and metagenomes), we have developed a comprehensive microarray, HuMiChip2, for strain-level identification and functional characterization of human microbiomes. HuMiChip2 was composed of 29,467 strain-specific probes targeting 2063 microbial strains/species and 133,924 sequence- and group-specific probes targeting 157 key functional gene families involved in various metabolic pathways and host-microbiome interaction processes. Computational evaluation of strain-specific probes suggested that they were not only specific to mock communities of sequenced microorganisms and metagenomes from different human body sites but also to non-sequenced microbial strains. Experimental evaluation of strain-specific probes using single strains/species and mock communities suggested a high specificity of these probes with their corresponding targets. Application of HuMiChip2 to human gut microbiome samples showed the patient microbiomes of alcoholic liver cirrhosis significantly (p < 0.05) shifted their functional structure from the healthy individuals, and the relative abundance of 21 gene families significantly (p < 0.1) differed between the liver cirrhosis patients and healthy individuals. At the strain level, five Bacteroides strains were significantly (p < 0.1) and more frequently detected in liver cirrhosis patients. These results suggest that the developed HuMiChip2 is a useful microbial ecological microarray for both strain-level identification and functional profiling of human microbiomes.}, }
@article {pmid27698613, year = {2016}, author = {Jones, RM}, title = {The Influence of the Gut Microbiota on Host Physiology: In Pursuit of Mechanisms.}, journal = {The Yale journal of biology and medicine}, volume = {89}, number = {3}, pages = {285-297}, pmid = {27698613}, issn = {1551-4056}, support = {R01 DK098391/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Bacteria/metabolism ; Gastrointestinal Microbiome/*physiology ; Humans ; Intestines/microbiology ; Probiotics/metabolism ; Stem Cells/immunology/metabolism ; }, abstract = {The results generated from the NIH funded Human Microbiome Project (HMP) are necessarily tied to the overall mission of the agency, which is to foster scientific discoveries as a basis for protecting and improving health. The investment in the HMP phase 1 accomplished many of its goals including the preliminary characterization of the human microbiome and the identification of links between microbiome diversity and disease states. Going forward, the next step in these studies must involve the identification of the functional molecular elements that mediate the positive influence of a eubiotic microbiome on health and disease. This review will focus on recent advances describing mechanistic events in the intestine elicited by the microbiome. These include symbiotic bacteria-induced activation of redox-dependent cell signaling, the bacterial production of short chain fatty acids and ensuing cellular responses, and the secretion of bacteriocins by bacteria that have anti-microbial activities against potential pathogens.}, }
@article {pmid27697111, year = {2016}, author = {Moon, JH and Lee, JH}, title = {Probing the diversity of healthy oral microbiome with bioinformatics approaches.}, journal = {BMB reports}, volume = {49}, number = {12}, pages = {662-670}, pmid = {27697111}, issn = {1976-670X}, mesh = {Aging ; Bacteria/genetics ; Climate ; *Computational Biology ; Databases, Genetic ; Humans ; *Microbiota ; Mouth/*microbiology ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; }, abstract = {The human oral cavity contains a highly personalized microbiome essential to maintaining health, but capable of causing oral and systemic diseases. Thus, an in-depth definition of "healthy oral microbiome" is critical to understanding variations in disease states from preclinical conditions, and disease onset through progressive states of disease. With rapid advances in DNA sequencing and analytical technologies, population-based studies have documented the range and diversity of both taxonomic compositions and functional potentials observed in the oral microbiome in healthy individuals. Besides factors specific to the host, such as age and race/ethnicity, environmental factors also appear to contribute to the variability of the healthy oral microbiome. Here, we review bioinformatic techniques for metagenomic datasets, including their strengths and limitations. In addition, we summarize the interpersonal and intrapersonal diversity of the oral microbiome, taking into consideration the recent large-scale and longitudinal studies, including the Human Microbiome Project. [BMB Reports 2016; 49(12): 662-670].}, }
@article {pmid27668170, year = {2016}, author = {Sung, J and Hale, V and Merkel, AC and Kim, PJ and Chia, N}, title = {Metabolic modeling with Big Data and the gut microbiome.}, journal = {Applied &amp; translational genomics}, volume = {10}, number = {}, pages = {10-15}, pmid = {27668170}, issn = {2212-0661}, support = {R01 CA179243/CA/NCI NIH HHS/United States ; }, abstract = {The recent advances in high-throughput omics technologies have enabled researchers to explore the intricacies of the human microbiome. On the clinical front, the gut microbial community has been the focus of many biomarker-discovery studies. While the recent deluge of high-throughput data in microbiome research has been vastly informative and groundbreaking, we have yet to capture the full potential of omics-based approaches. Realizing the promise of multi-omics data will require integration of disparate omics data, as well as a biologically relevant, mechanistic framework - or metabolic model - on which to overlay these data. Also, a new paradigm for metabolic model evaluation is necessary. Herein, we outline the need for multi-omics data integration, as well as the accompanying challenges. Furthermore, we present a framework for characterizing the ecology of the gut microbiome based on metabolic network modeling.}, }
@article {pmid27602409, year = {2016}, author = {McDonald, D and Ackermann, G and Khailova, L and Baird, C and Heyland, D and Kozar, R and Lemieux, M and Derenski, K and King, J and Vis-Kampen, C and Knight, R and Wischmeyer, PE}, title = {Extreme Dysbiosis of the Microbiome in Critical Illness.}, journal = {mSphere}, volume = {1}, number = {4}, pages = {}, pmid = {27602409}, issn = {2379-5042}, abstract = {Critical illness is hypothesized to associate with loss of "health-promoting" commensal microbes and overgrowth of pathogenic bacteria (dysbiosis). This dysbiosis is believed to increase susceptibility to nosocomial infections, sepsis, and organ failure. A trial with prospective monitoring of the intensive care unit (ICU) patient microbiome using culture-independent techniques to confirm and characterize this dysbiosis is thus urgently needed. Characterizing ICU patient microbiome changes may provide first steps toward the development of diagnostic and therapeutic interventions using microbiome signatures. To characterize the ICU patient microbiome, we collected fecal, oral, and skin samples from 115 mixed ICU patients across four centers in the United States and Canada. Samples were collected at two time points: within 48 h of ICU admission, and at ICU discharge or on ICU day 10. Sample collection and processing were performed according to Earth Microbiome Project protocols. We applied SourceTracker to assess the source composition of ICU patient samples by using Qiita, including samples from the American Gut Project (AGP), mammalian corpse decomposition samples, childhood (Global Gut study), and house surfaces. Our results demonstrate that critical illness leads to significant and rapid dysbiosis. Many taxons significantly depleted from ICU patients versus AGP healthy controls are key "health-promoting" organisms, and overgrowth of known pathogens was frequent. Source compositions of ICU patient samples are largely uncharacteristic of the expected community type. Between time points and within a patient, the source composition changed dramatically. Our initial results show great promise for microbiome signatures as diagnostic markers and guides to therapeutic interventions in the ICU to repopulate the normal, "health-promoting" microbiome and thereby improve patient outcomes. IMPORTANCE Critical illness may be associated with the loss of normal, "health promoting" bacteria, allowing overgrowth of disease-promoting pathogenic bacteria (dysbiosis), which, in turn, makes patients susceptible to hospital-acquired infections, sepsis, and organ failure. This has significant world health implications, because sepsis is becoming a leading cause of death worldwide, and hospital-acquired infections contribute to significant illness and increased costs. Thus, a trial that monitors the ICU patient microbiome to confirm and characterize this hypothesis is urgently needed. Our study analyzed the microbiomes of 115 critically ill subjects and demonstrated rapid dysbiosis from unexpected environmental sources after ICU admission. These data may provide the first steps toward defining targeted therapies that correct potentially "illness-promoting" dysbiosis with probiotics or with targeted, multimicrobe synthetic "stool pills" that restore a healthy microbiome in the ICU setting to improve patient outcomes.}, }
@article {pmid27572971, year = {2016}, author = {Donati, C and Zolfo, M and Albanese, D and Tin Truong, D and Asnicar, F and Iebba, V and Cavalieri, D and Jousson, O and De Filippo, C and Huttenhower, C and Segata, N}, title = {Uncovering oral Neisseria tropism and persistence using metagenomic sequencing.}, journal = {Nature microbiology}, volume = {1}, number = {7}, pages = {16070}, pmid = {27572971}, issn = {2058-5276}, support = {R01 HG005969/HG/NHGRI NIH HHS/United States ; U54 DE023798/DE/NIDCR NIH HHS/United States ; }, mesh = {Computers, Molecular ; Genome, Bacterial ; Gingiva/microbiology ; Humans ; *Metagenome ; Metagenomics/methods ; Microbiota ; Mouth/*microbiology ; Multilocus Sequence Typing ; Neisseria/classification/genetics/isolation &amp; purification/*physiology ; Pharynx/microbiology ; Phylogeny ; Polymorphism, Single Nucleotide ; *Sequence Analysis, DNA ; Tongue/microbiology ; *Viral Tropism ; }, abstract = {Microbial epidemiology and population genomics have previously been carried out near-exclusively for organisms grown in vitro. Metagenomics helps to overcome this limitation, but it is still challenging to achieve strain-level characterization of microorganisms from culture-independent data with sufficient resolution for epidemiological modelling. Here, we have developed multiple complementary approaches that can be combined to profile and track individual microbial strains. To specifically profile highly recombinant neisseriae from oral metagenomes, we integrated four metagenomic analysis techniques: single nucleotide polymorphisms in the clade's core genome, DNA uptake sequence signatures, metagenomic multilocus sequence typing and strain-specific marker genes. We applied these tools to 520 oral metagenomes from the Human Microbiome Project, finding evidence of site tropism and temporal intra-subject strain retention. Although the opportunistic pathogen Neisseria meningitidis is enriched for colonization in the throat, N. flavescens and N. subflava populate the tongue dorsum, and N. sicca, N. mucosa and N. elongata the gingival plaque. The buccal mucosa appeared as an intermediate ecological niche between the plaque and the tongue. The resulting approaches to metagenomic strain profiling are generalizable and can be extended to other organisms and microbiomes across environments.}, }
@article {pmid27527985, year = {2016}, author = {Li, L and Ma, ZS}, title = {Testing the Neutral Theory of Biodiversity with Human Microbiome Datasets.}, journal = {Scientific reports}, volume = {6}, number = {}, pages = {31448}, pmid = {27527985}, issn = {2045-2322}, mesh = {Bacteria/*classification ; *Biota ; Humans ; *Microbiota ; Models, Biological ; }, abstract = {The human microbiome project (HMP) has made it possible to test important ecological theories for arguably the most important ecosystem to human health-the human microbiome. Existing limited number of studies have reported conflicting evidence in the case of the neutral theory; the present study aims to comprehensively test the neutral theory with extensive HMP datasets covering all five major body sites inhabited by the human microbiome. Utilizing 7437 datasets of bacterial community samples, we discovered that only 49 communities (less than 1%) satisfied the neutral theory, and concluded that human microbial communities are not neutral in general. The 49 positive cases, although only a tiny minority, do demonstrate the existence of neutral processes. We realize that the traditional doctrine of microbial biogeography "Everything is everywhere, but the environment selects" first proposed by Baas-Becking resolves the apparent contradiction. The first part of Baas-Becking doctrine states that microbes are not dispersal-limited and therefore are neutral prone, and the second part reiterates that the freely dispersed microbes must endure selection by the environment. Therefore, in most cases, it is the host environment that ultimately shapes the community assembly and tip the human microbiome to niche regime.}, }
@article {pmid27496318, year = {2017}, author = {Twigg, HL and Weinstock, GM and Knox, KS}, title = {Lung microbiome in human immunodeficiency virus infection.}, journal = {Translational research : the journal of laboratory and clinical medicine}, volume = {179}, number = {}, pages = {97-107}, pmid = {27496318}, issn = {1878-1810}, support = {U01 HL098960/HL/NHLBI NIH HHS/United States ; U01 HL121831/HL/NHLBI NIH HHS/United States ; }, mesh = {HIV Infections/*microbiology/virology ; Humans ; Lung/immunology/*microbiology/pathology/*virology ; *Microbiota ; Pneumonia/microbiology/pathology ; Treatment Outcome ; }, abstract = {The lung microbiome plays a significant role in normal lung function and disease. Because microbial colonization is likely influenced by immunodeficiency, one would speculate that infection with human immunodeficiency virus (HIV) alters the lung microbiome. Furthermore, how this alteration might impact pulmonary complications now seen in HIV-infected patients on antiretroviral therapy (ART), which has shifted from opportunistic infections to diseases associated with chronic inflammation, is not known. There have been limited publications on the lung microbiome in HIV infection, many of them emanating from the Lung HIV Microbiome Project. Current evidence suggests that the lung microbiome in healthy HIV-infected individuals with preserved CD4 counts is similar to uninfected individuals. However, in individuals with more advanced disease, there is an altered alveolar microbiome characterized by a loss of richness and evenness (alpha diversity) within individuals. Furthermore, as a group the taxa making up the HIV-infected and uninfected lung microbiome are different (differences in beta diversity), and the HIV-infected population is more spread out (greater dispersion) than the uninfected population. These differences decline with ART, but even after effective therapy the alveolar microbiome in HIV-infected individuals contains increased amounts of signature bacteria, some of which have previously been associated with chronic lung inflammation. Furthermore, more recent investigations into the lung virome in HIV infection suggest that perturbations in lung viral communities also exist in HIV infection, and that these too are associated with evidence of lung inflammation. Thus, it is likely both microbiome and virome alterations in HIV infection contribute to lung inflammation in these individuals, which has important implications on the changing spectrum of pulmonary complications in patients living with HIV.}, }
@article {pmid27363992, year = {2016}, author = {Lau, JT and Whelan, FJ and Herath, I and Lee, CH and Collins, SM and Bercik, P and Surette, MG}, title = {Capturing the diversity of the human gut microbiota through culture-enriched molecular profiling.}, journal = {Genome medicine}, volume = {8}, number = {1}, pages = {72}, pmid = {27363992}, issn = {1756-994X}, mesh = {Aerobiosis ; Anaerobiosis ; Bacteria/classification/*genetics/isolation &amp; purification ; Biodiversity ; *Cell Culture Techniques ; Clostridiales/classification/*genetics/growth &amp; development/isolation &amp; purification ; Feces/microbiology ; Gastrointestinal Microbiome/*genetics ; Gastrointestinal Tract/microbiology ; *Genes, Bacterial ; Healthy Volunteers ; Humans ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; }, abstract = {BACKGROUND: The human gut microbiota has been implicated in most aspects of health and disease; however, most of the bacteria in this community are considered unculturable, so studies have relied on molecular-based methods. These methods generally do not permit the isolation of organisms, which is required to fully explore the functional roles of bacteria for definitive association with host phenotypes. Using a combination of culture and 16S rRNA gene sequencing, referred to as culture-enriched molecular profiling, we show that the majority of the bacteria identified by 16S sequencing of the human gut microbiota can be cultured.<br><br>METHODS: Five fresh, anaerobic fecal samples were cultured using 33 media and incubation of plates anaerobically and aerobically resulted in 66 culture conditions for culture-enriched molecular profiling. The cultivable portion of the fecal microbiota was determined by comparing the operational taxonomic units (OTUs) recovered by 16S sequencing of the culture plates to OTUs from culture-independent sequencing of the fecal sample. Targeted isolation of Lachnospiraceae strains using conditions defined by culture-enriched molecular profiling was carried out on two fresh stool samples.<br><br>RESULTS: We show that culture-enriched molecular profiling, utilizing 66 culture conditions combined with 16S rRNA gene sequencing, allowed for the culturing of an average of 95&#xa0;% of the OTUs present at greater than 0.1&#xa0;% abundance in fecal samples. Uncultured OTUs were low abundance in stool. Importantly, comparing culture-enrichment to culture-independent sequencing revealed that the majority of OTUs were detected only by culture, highlighting the advantage of culture for studying the diversity of the gut microbiota. Applying culture-enriched molecular profiling to target Lachnospiraceae strains resulted in the recovery of 79 isolates, 12 of which are on the Human Microbiome Project's "Most Wanted" list.<br><br>CONCLUSIONS: We show that, through culture-enriched molecular profiling, the majority of the bacteria in the human gut microbiota can be cultured and this method revealed greater bacterial diversity compared to culture-independent sequencing. Additionally, this method could be applied for the targeted recovery of a specific bacterial group. This approach allows for the isolation of bacteria of interest from the gut microbiota, providing new opportunities to explore mechanisms of microbiota-host interactions and the diversity of the human microbiota.}, }
@article {pmid27350143, year = {2016}, author = {Proctor, LM}, title = {The National Institutes of Health Human Microbiome Project.}, journal = {Seminars in fetal &amp; neonatal medicine}, volume = {21}, number = {6}, pages = {368-372}, doi = {10.1016/j.siny.2016.05.002}, pmid = {27350143}, issn = {1878-0946}, mesh = {Humans ; *Microbiota ; National Institutes of Health (U.S.) ; United States ; }, abstract = {This overview describes the impetus for and the goals of the National Institutes of Health (NIH)'s Human Microbiome Project (HMP) and the research resources available through the HMP. As the HMP also serves as a catalyst for human microbiome research at the NIH, NIH Institutes and Centers support for this field is also briefly addressed.}, }
@article {pmid27339941, year = {2016}, author = {Ma, Y and Hu, X and He, T and Jiang, X}, title = {Hessian regularization based symmetric nonnegative matrix factorization for clustering gene expression and microbiome data.}, journal = {Methods (San Diego, Calif.)}, volume = {111}, number = {}, pages = {80-84}, doi = {10.1016/j.ymeth.2016.06.017}, pmid = {27339941}, issn = {1095-9130}, mesh = {*Algorithms ; *Cluster Analysis ; Gene Expression/genetics ; Gene Expression Profiling/*methods/statistics &amp; numerical data ; Humans ; Microbiota/*genetics ; }, abstract = {Nonnegative matrix factorization (NMF) has received considerable attention due to its interpretation of observed samples as combinations of different components, and has been successfully used as a clustering method. As an extension of NMF, Symmetric NMF (SNMF) inherits the advantages of NMF. Unlike NMF, however, SNMF takes a nonnegative similarity matrix as an input, and two lower rank nonnegative matrices (H, H[T]) are computed as an output to approximate the original similarity matrix. Laplacian regularization has improved the clustering performance of NMF and SNMF. However, Laplacian regularization (LR), as a classic manifold regularization method, suffers some problems because of its weak extrapolating ability. In this paper, we propose a novel variant of SNMF, called Hessian regularization based symmetric nonnegative matrix factorization (HSNMF), for this purpose. In contrast to Laplacian regularization, Hessian regularization fits the data perfectly and extrapolates nicely to unseen data. We conduct extensive experiments on several datasets including text data, gene expression data and HMP (Human Microbiome Project) data. The results show that the proposed method outperforms other methods, which suggests the potential application of HSNMF in biological data clustering.}, }
@article {pmid27303377, year = {2016}, author = {Jeraldo, P and Hernandez, A and Nielsen, HB and Chen, X and White, BA and Goldenfeld, N and Nelson, H and Alhquist, D and Boardman, L and Chia, N}, title = {Capturing One of the Human Gut Microbiome's Most Wanted: Reconstructing the Genome of a Novel Butyrate-Producing, Clostridial Scavenger from Metagenomic Sequence Data.}, journal = {Frontiers in microbiology}, volume = {7}, number = {}, pages = {783}, pmid = {27303377}, issn = {1664-302X}, support = {P30 DK084567/DK/NIDDK NIH HHS/United States ; R01 CA179243/CA/NCI NIH HHS/United States ; }, abstract = {The role of the microbiome in health and disease is attracting great attention, yet we still know little about some of the most prevalent microorganisms inside our bodies. Several years ago, Human Microbiome Project (HMP) researchers generated a list of "most wanted" taxa: bacteria both prevalent among healthy volunteers and distantly related to any sequenced organisms. Unfortunately, the challenge of assembling high-quality genomes from a tangle of metagenomic reads has slowed progress in learning about these uncultured bacteria. Here, we describe how recent advances in sequencing and analysis allowed us to assemble "most wanted" genomes from metagenomic data collected from four stool samples. Using a combination of both de novo and guided assembly methods, we assembled and binned over 100 genomes from an initial data set of over 1,300 Gbp. One of these genome bins, which met HMP's criteria for a "most wanted" taxa, contained three essentially complete genomes belonging to a previously uncultivated species. This species is most closely related to Eubacterium desmolans and the clostridial cluster IV/Clostridium leptum subgroup species Butyricicoccus pullicaecorum (71-76% average nucleotide identity). Gene function analysis indicates that the species is an obligate anaerobe, forms spores, and produces the anti-inflammatory short-chain fatty acids acetate and butyrate. It also appears to take up metabolically costly molecules such as cobalamin, methionine, and branch-chained amino acids from the environment, and to lack virulence genes. Thus, the evidence is consistent with a secondary degrader that occupies a host-dependent, nutrient-scavenging niche within the gut; its ability to produce butyrate, which is thought to play an anti-inflammatory role, makes it intriguing for the study of diseases such as colon cancer and inflammatory bowel disease. In conclusion, we have assembled essentially complete genomes from stool metagenomic data, yielding valuable information about uncultured organisms' metabolic and ecologic niches, factors that may be required to successfully culture these bacteria, and their role in maintaining health and causing disease.}, }
@article {pmid27279224, year = {2016}, author = {Bashan, A and Gibson, TE and Friedman, J and Carey, VJ and Weiss, ST and Hohmann, EL and Liu, YY}, title = {Universality of human microbial dynamics.}, journal = {Nature}, volume = {534}, number = {7606}, pages = {259-262}, pmid = {27279224}, issn = {1476-4687}, support = {R01 HL091528/HL/NHLBI NIH HHS/United States ; }, mesh = {Clostridioides difficile/physiology ; Clostridium Infections/microbiology ; Computer Simulation ; Cross-Sectional Studies ; Datasets as Topic ; *Ecosystem ; Environment ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/physiology ; Healthy Volunteers ; Humans ; Intestines/microbiology ; Metagenomics ; Microbiota/*physiology ; Mouth/microbiology ; Organ Specificity ; Skin/microbiology ; Species Specificity ; }, abstract = {Human-associated microbial communities have a crucial role in determining our health and well-being, and this has led to the continuing development of microbiome-based therapies such as faecal microbiota transplantation. These microbial communities are very complex, dynamic and highly personalized ecosystems, exhibiting a high degree of inter-individual variability in both species assemblages and abundance profiles. It is not known whether the underlying ecological dynamics of these communities, which can be parameterized by growth rates, and intra- and inter-species interactions in population dynamics models, are largely host-independent (that is, universal) or host-specific. If the inter-individual variability reflects host-specific dynamics due to differences in host lifestyle, physiology or genetics, then generic microbiome manipulations may have unintended consequences, rendering them ineffective or even detrimental. Alternatively, microbial ecosystems of different subjects may exhibit universal dynamics, with the inter-individual variability mainly originating from differences in the sets of colonizing species. Here we develop a new computational method to characterize human microbial dynamics. By applying this method to cross-sectional data from two large-scale metagenomic studies--the Human Microbiome Project and the Student Microbiome Project--we show that gut and mouth microbiomes display pronounced universal dynamics, whereas communities associated with certain skin sites are probably shaped by differences in the host environment. Notably, the universality of gut microbial dynamics is not observed in subjects with recurrent Clostridium difficile infection but is observed in the same set of subjects after faecal microbiota transplantation. These results fundamentally improve our understanding of the processes that shape human microbial ecosystems, and pave the way to designing general microbiome-based therapies.}, }
@article {pmid27245597, year = {2018}, author = {Cundell, AM}, title = {Microbial Ecology of the Human Skin.}, journal = {Microbial ecology}, volume = {76}, number = {1}, pages = {113-120}, pmid = {27245597}, issn = {1432-184X}, mesh = {Age Factors ; Anti-Bacterial Agents ; Axilla/microbiology ; Bacteria/classification/genetics ; Bacterial Physiological Phenomena ; *Biodiversity ; Cosmetics ; *Ecology ; *Ecosystem ; Fungi/classification/genetics/physiology ; Genes, Bacterial/genetics ; Genes, Fungal/genetics ; Health Status ; Homeostasis ; Humans ; Injections ; Microbiota/genetics/*physiology ; Perineum/microbiology ; RNA, Ribosomal, 16S/genetics ; Sex Factors ; Skin/*microbiology ; Toe Joint/microbiology ; Vaccination ; }, abstract = {This review article on the skin microbiota was written in response to recent advances that transitioned from culture methods to PCR amplification and sequencing of bacterial and fungal genes as a result of the Human Microbiome Project. This transition enables the investigation of the full diversity of microorganisms inhabiting human skin. The skin provides a range of habitats with different microbiota associated with the three major regions of the skin, namely the moist axilla, perineum, and toe webs; oily or sebaceous head, neck, and trunk; and dry forearms and legs. These new culture-independent tools are revealing the diversity of the human skin microbiota in the different locations of the body and with skin depth. These tools should lead to a better understanding of the state of homeostasis between the microbiota and the host and the overall functionality of that microbiota.}, }
@article {pmid29878736, year = {2016}, author = {Lin, Z and Zu, XP and Xie, HS and Jin, HZ and Yang, N and Liu, XR and Zhang, WD}, title = {[Research progress in mechanism of intestinal microorganisms in human diseases].}, journal = {Yao xue xue bao = Acta pharmaceutica Sinica}, volume = {51}, number = {6}, pages = {843-852}, pmid = {29878736}, issn = {0513-4870}, mesh = {*Gastrointestinal Microbiome ; Humans ; Intestines/*microbiology ; *Metagenomics ; Symbiosis ; }, abstract = {The international cooperated research projects of the Human Microbiome Project (HMP) and Metagenomics of The Human Intestinal Tract (MetaHIT) were officially launched in 2007, which indicated the era of metagenomics research of microorganisms in human gastrointestinal tract had been coming. Each human body is a superorganism which is composed of 90% commensal microorganisms, especially the intestinal microorganisms. The intestinal microorganisms play an important role on health maintenance since they are involved in the absorption and metabolism of nutrients in the human bodies. Herein, we review the research progress in the mechanism of intestinal microorganisms in human diseases. Our purpose is to provide novel ideas on human health and therapeutic targets of diseases.}, }
@article {pmid27220974, year = {2016}, author = {Pylro, VS and Morais, DK and de Oliveira, FS and Dos Santos, FG and Lemos, LN and Oliveira, G and Roesch, LF}, title = {BMPOS: a Flexible and User-Friendly Tool Sets for Microbiome Studies.}, journal = {Microbial ecology}, volume = {72}, number = {2}, pages = {443-447}, pmid = {27220974}, issn = {1432-184X}, mesh = {Bacteriological Techniques ; Brazil ; Databases, Genetic ; Genetic Markers ; High-Throughput Nucleotide Sequencing/*methods ; Metagenomics/*methods ; *Microbiota ; Phylogeny ; Sequence Analysis, DNA ; *Software ; }, abstract = {Recent advances in science and technology are leading to a revision and re-orientation of methodologies, addressing old and current issues under a new perspective. Advances in next generation sequencing (NGS) are allowing comparative analysis of the abundance and diversity of whole microbial communities, generating a large amount of data and findings at a systems level. The current limitation for biologists has been the increasing demand for computational power and training required for processing of NGS data. Here, we describe the deployment of the Brazilian Microbiome Project Operating System (BMPOS), a flexible and user-friendly Linux distribution dedicated to microbiome studies. The Brazilian Microbiome Project (BMP) has developed data analyses pipelines for metagenomic studies (phylogenetic marker genes), conducted using the two main high-throughput sequencing platforms (Ion Torrent and Illumina MiSeq). The BMPOS is freely available and possesses the entire requirement of bioinformatics packages and databases to perform all the pipelines suggested by the BMP team. The BMPOS may be used as a bootable live USB stick or installed in any computer with at least 1 GHz CPU and 512 MB RAM, independent of the operating system previously installed. The BMPOS has proved to be effective for sequences processing, sequences clustering, alignment, taxonomic annotation, statistical analysis, and plotting of metagenomic data. The BMPOS has been used during several metagenomic analyses courses, being valuable as a tool for training, and an excellent starting point to anyone interested in performing metagenomic studies. The BMPOS and its documentation are available at http://www.brmicrobiome.org .}, }
@article {pmid27182288, year = {2016}, author = {Thomas-White, K and Brady, M and Wolfe, AJ and Mueller, ER}, title = {The bladder is not sterile: History and current discoveries on the urinary microbiome.}, journal = {Current bladder dysfunction reports}, volume = {11}, number = {1}, pages = {18-24}, pmid = {27182288}, issn = {1931-7212}, support = {R01 DK104718/DK/NIDDK NIH HHS/United States ; R21 DK097435/DK/NIDDK NIH HHS/United States ; }, abstract = {In the human body, there are 10 bacterial cells for every one human cell. This fact highlights the importance of the National institutes of Health's initiative to map the human microbiome. The Human Microbiome Project was the first large-scale mapping of the human microbiome of 5 body sites: GI tract, mouth, vagina, skin and nasal cavity using culture-independent methods. The bladder was not originally tested because it was considered to be sterile and there were complexities regarding sample collection. Over the last couple years our team along with other investigators have shown that a urinary microbiome exists and for most individuals it plays a protective role.}, }
@article {pmid27152251, year = {2016}, author = {Cross, B and Faustoferri, RC and Quivey, RG}, title = {What are We Learning and What Can We Learn from the Human Oral Microbiome Project?.}, journal = {Current oral health reports}, volume = {3}, number = {1}, pages = {56-63}, pmid = {27152251}, issn = {2196-3002}, support = {R01 DE013683/DE/NIDCR NIH HHS/United States ; R01 DE017157/DE/NIDCR NIH HHS/United States ; T90 DE021985/DE/NIDCR NIH HHS/United States ; }, abstract = {Extraordinary technological advances have greatly accelerated our ability to identify bacteria, at the species level, present in clinical samples taken from the human mouth. In addition, technologies are evolving such that the oral samples can be analyzed for their protein and metabolic products. As a result, pictures are the advent of personalized dental medicine is becoming closer to reality.}, }
@article {pmid27148241, year = {2016}, author = {Utter, DR and Mark Welch, JL and Borisy, GG}, title = {Individuality, Stability, and Variability of the Plaque Microbiome.}, journal = {Frontiers in microbiology}, volume = {7}, number = {}, pages = {564}, pmid = {27148241}, issn = {1664-302X}, support = {R01 DE022586/DE/NIDCR NIH HHS/United States ; }, abstract = {Dental plaque is a bacterial biofilm composed of a characteristic set of organisms. Relatively little information from cultivation-independent, high-throughput analyses has been published on the temporal dynamics of the dental plaque microbiome. We used Minimum Entropy Decomposition, an information theory-based approach similar to oligotyping that provides single-nucleotide resolution, to analyze a previously published time series data set and investigate the dynamics of the plaque microbiome at various analytic and taxonomic levels. At both the genus and 97% Operational Taxonomic Unit (OTU) levels of resolution, the range of variation within each individual overlapped that of other individuals in the data set. When analyzed at the oligotype level, however, the overlap largely disappeared, showing that single-nucleotide resolution enables differentiation of individuals from one another without ambiguity. The overwhelming majority of the plaque community in all samples was made up of bacteria from a moderate number of plaque-typical genera, indicating that the overall community framework is shared among individuals. Each of these genera fluctuated in abundance around a stable mean that varied between individuals, with some genera having higher inter-individual variability than others. Thus, at the genus level, differences between individuals lay not in the identity of the major genera but in consistently differing proportions of these genera from mouth to mouth. However, at the oligotype level, we detected oligotype "fingerprints," a highly individual-specific set of persistently abundant oligotypes fluctuating around a stable mean over time. For example, within the genus Corynebacterium, more than a dozen oligotypes were detectable in each individual, of which a different subset reached high abundance in any given person. This pattern suggests that each mouth contains a subtly different community of organisms. We also compared the Chinese plaque community characterized here to previously characterized Western plaque communities, as represented by analyses of data emerging from the Human Microbiome Project, and found no major differences between Chinese and Western supragingival plaque. In conclusion, we found the plaque microbiome to be highly individualized at the oligotype level and characterized by stability of community membership, with variability in the relative abundance of community members between individuals and over time.}, }
@article {pmid27143475, year = {2016}, author = {Gloor, GB and Wu, JR and Pawlowsky-Glahn, V and Egozcue, JJ}, title = {It's all relative: analyzing microbiome data as compositions.}, journal = {Annals of epidemiology}, volume = {26}, number = {5}, pages = {322-329}, doi = {10.1016/j.annepidem.2016.03.003}, pmid = {27143475}, issn = {1873-2585}, support = {//CIHR/Canada ; }, mesh = {Datasets as Topic ; Female ; High-Throughput Nucleotide Sequencing/*methods ; Humans ; Male ; Microbiota/*genetics ; RNA, Ribosomal, 16S/*genetics ; Sensitivity and Specificity ; }, abstract = {PURPOSE: The ability to properly analyze and interpret large microbiome data sets has lagged behind our ability to acquire such data sets from environmental or clinical samples. Sequencing instruments impose a structure on these data: the natural sample space of a 16S rRNA gene sequencing data set is a simplex, which is a part of real space that is restricted to nonnegative values with a constant sum. Such data are compositional and should be analyzed using compositionally appropriate tools and approaches. However, most of the tools for 16S rRNA gene sequencing analysis assume these data are unrestricted.<br><br>METHODS: We show that existing tools for compositional data (CoDa) analysis can be readily adapted to analyze high-throughput sequencing data sets.<br><br>RESULTS: The Human Microbiome Project tongue versus buccal mucosa data set shows how the CoDa approach can address the major elements of microbiome analysis. Reanalysis of a publicly available autism microbiome data set shows that the CoDa approach in concert with multiple hypothesis test corrections prevent false positive identifications.<br><br>CONCLUSIONS: The CoDa approach is readily scalable to microbiome-sized analyses. We provide example code and make recommendations to improve the analysis and reporting of microbiome data sets.}, }
@article {pmid27124399, year = {2016}, author = {Tandon, D and Haque, MM and Mande, SS}, title = {Inferring Intra-Community Microbial Interaction Patterns from Metagenomic Datasets Using Associative Rule Mining Techniques.}, journal = {PloS one}, volume = {11}, number = {4}, pages = {e0154493}, pmid = {27124399}, issn = {1932-6203}, mesh = {Algorithms ; Data Mining/*methods ; Databases, Genetic ; Gastrointestinal Microbiome ; Humans ; *Metagenome ; *Microbial Interactions ; Web Browser ; }, abstract = {The nature of inter-microbial metabolic interactions defines the stability of microbial communities residing in any ecological niche. Deciphering these interaction patterns is crucial for understanding the mode/mechanism(s) through which an individual microbial community transitions from one state to another (e.g. from a healthy to a diseased state). Statistical correlation techniques have been traditionally employed for mining microbial interaction patterns from taxonomic abundance data corresponding to a given microbial community. In spite of their efficiency, these correlation techniques can capture only 'pair-wise interactions'. Moreover, their emphasis on statistical significance can potentially result in missing out on several interactions that are relevant from a biological standpoint. This study explores the applicability of one of the earliest association rule mining algorithm i.e. the 'Apriori algorithm' for deriving 'microbial association rules' from the taxonomic profile of given microbial community. The classical Apriori approach derives association rules by analysing patterns of co-occurrence/co-exclusion between various '(subsets of) features/items' across various samples. Using real-world microbiome data, the efficiency/utility of this rule mining approach in deciphering multiple (biologically meaningful) association patterns between 'subsets/subgroups' of microbes (constituting microbiome samples) is demonstrated. As an example, association rules derived from publicly available gut microbiome datasets indicate an association between a group of microbes (Faecalibacterium, Dorea, and Blautia) that are known to have mutualistic metabolic associations among themselves. Application of the rule mining approach on gut microbiomes (sourced from the Human Microbiome Project) further indicated similar microbial association patterns in gut microbiomes irrespective of the gender of the subjects. A Linux implementation of the Association Rule Mining (ARM) software (customised for deriving 'microbial association rules' from microbiome data) is freely available for download from the following link: http://metagenomics.atc.tcs.com/arm.}, }
@article {pmid27123663, year = {2016}, author = {Wolf, PG and Biswas, A and Morales, SE and Greening, C and Gaskins, HR}, title = {H2 metabolism is widespread and diverse among human colonic microbes.}, journal = {Gut microbes}, volume = {7}, number = {3}, pages = {235-245}, pmid = {27123663}, issn = {1949-0984}, mesh = {Bacteria/*classification/*metabolism ; Carbohydrate Metabolism ; Colon/*microbiology ; Feces/microbiology ; Fermentation ; Healthy Volunteers ; Humans ; Hydrogen/*metabolism ; Hydrogenase/metabolism ; Metabolic Networks and Pathways ; }, abstract = {Microbial molecular hydrogen (H2) cycling is central to metabolic homeostasis and microbial composition in the human gastrointestinal tract. Molecular H2 is produced as an endproduct of carbohydrate fermentation and is reoxidised primarily by sulfate-reduction, acetogenesis, and methanogenesis. However, the enzymatic basis for these processes is incompletely understood and the hydrogenases responsible have not been investigated. In this work, we surveyed the genomic and metagenomic distribution of hydrogenase-encoding genes in the human colon to infer dominant mechanisms of H2 cycling. The data demonstrate that 70% of gastrointestinal microbial species listed in the Human Microbiome Project encode the genetic capacity to metabolise H2. A wide variety of anaerobically-adapted hydrogenases were present, with [FeFe]-hydrogenases predominant. We subsequently analyzed the hydrogenase gene content of stools from 20 healthy human subjects. The hydrogenase gene content of all samples was overwhelmingly dominated by fermentative and electron-bifurcating [FeFe]-hydrogenases emerging from the Bacteroidetes and Firmicutes. This study supports that H2 metabolism in the human gut is driven by fermentative H2 production and interspecies H2 transfer. However, it suggests that electron-bifurcation rather than respiration is the dominant mechanism of H2 reoxidation in the human colon, generating reduced ferredoxin to sustain carbon-fixation (e.g. acetogenesis) and respiration (via the Rnf complex). This work provides the first comprehensive bioinformatic insight into the mechanisms of H2 metabolism in the human colon.}, }
@article {pmid27122046, year = {2016}, author = {Lloyd-Price, J and Abu-Ali, G and Huttenhower, C}, title = {The healthy human microbiome.}, journal = {Genome medicine}, volume = {8}, number = {1}, pages = {51}, pmid = {27122046}, issn = {1756-994X}, mesh = {Bacteria/*classification/*genetics ; Genetic Variation ; Healthy Volunteers ; Humans ; Metagenome ; *Microbiota ; Phylogeny ; Phylogeography ; }, abstract = {Humans are virtually identical in their genetic makeup, yet the small differences in our DNA give rise to tremendous phenotypic diversity across the human population. By contrast, the metagenome of the human microbiome-the total DNA content of microbes inhabiting our bodies-is quite a bit more variable, with only a third of its constituent genes found in a majority of healthy individuals. Understanding this variability in the "healthy microbiome" has thus been a major challenge in microbiome research, dating back at least to the 1960s, continuing through the Human Microbiome Project and beyond. Cataloguing the necessary and sufficient sets of microbiome features that support health, and the normal ranges of these features in healthy populations, is an essential first step to identifying and correcting microbial configurations that are implicated in disease. Toward this goal, several population-scale studies have documented the ranges and diversity of both taxonomic compositions and functional potentials normally observed in the microbiomes of healthy populations, along with possible driving factors such as geography, diet, and lifestyle. Here, we review several definitions of a 'healthy microbiome' that have emerged, the current understanding of the ranges of healthy microbial diversity, and gaps such as the characterization of molecular function and the development of ecological therapies to be addressed in the future.}, }
@article {pmid27114874, year = {2016}, author = {Trembath-Reichert, E and Case, DH and Orphan, VJ}, title = {Characterization of microbial associations with methanotrophic archaea and sulfate-reducing bacteria through statistical comparison of nested Magneto-FISH enrichments.}, journal = {PeerJ}, volume = {4}, number = {}, pages = {e1913}, pmid = {27114874}, issn = {2167-8359}, support = {T32 GM007616/GM/NIGMS NIH HHS/United States ; }, abstract = {Methane seep systems along continental margins host diverse and dynamic microbial assemblages, sustained in large part through the microbially mediated process of sulfate-coupled Anaerobic Oxidation of Methane (AOM). This methanotrophic metabolism has been linked to consortia of anaerobic methane-oxidizing archaea (ANME) and sulfate-reducing bacteria (SRB). These two groups are the focus of numerous studies; however, less is known about the wide diversity of other seep associated microorganisms. We selected a hierarchical set of FISH probes targeting a range of Deltaproteobacteria diversity. Using the Magneto-FISH enrichment technique, we then magnetically captured CARD-FISH hybridized cells and their physically associated microorganisms from a methane seep sediment incubation. DNA from nested Magneto-FISH experiments was analyzed using Illumina tag 16S rRNA gene sequencing (iTag). Enrichment success and potential bias with iTag was evaluated in the context of full-length 16S rRNA gene clone libraries, CARD-FISH, functional gene clone libraries, and iTag mock communities. We determined commonly used Earth Microbiome Project (EMP) iTAG primers introduced bias in some common methane seep microbial taxa that reduced the ability to directly compare OTU relative abundances within a sample, but comparison of relative abundances between samples (in nearly all cases) and whole community-based analyses were robust. The iTag dataset was subjected to statistical co-occurrence measures of the most abundant OTUs to determine which taxa in this dataset were most correlated across all samples. Many non-canonical microbial partnerships were statistically significant in our co-occurrence network analysis, most of which were not recovered with conventional clone library sequencing, demonstrating the utility of combining Magneto-FISH and iTag sequencing methods for hypothesis generation of associations within complex microbial communities. Network analysis pointed to many co-occurrences containing putatively heterotrophic, candidate phyla such as OD1, Atribacteria, MBG-B, and Hyd24-12 and the potential for complex sulfur cycling involving Epsilon-, Delta-, and Gammaproteobacteria in methane seep ecosystems.}, }
@article {pmid27110483, year = {2016}, author = {Heiman, ML and Greenway, FL}, title = {A healthy gastrointestinal microbiome is dependent on dietary diversity.}, journal = {Molecular metabolism}, volume = {5}, number = {5}, pages = {317-320}, pmid = {27110483}, issn = {2212-8778}, abstract = {BACKGROUND: Like all healthy ecosystems, richness of microbiota species characterizes the GI microbiome in healthy individuals. Conversely, a loss in spe