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Bibliography on: Human Microbiome

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ESP: PubMed Auto Bibliography 02 Dec 2023 at 01:50 Created: 

Human Microbiome

The human microbiome is the set of all microbes that live on or in humans. Together, a human body and its associated microbiomes constitute a human holobiont. Although a human holobiont is mostly mammal by weight, by cell count it is mostly microbial. The number of microbial genes in the associated microbiomes far outnumber the number of human genes in the human genome. Just as humans (and other multicellular eukaryotes) evolved in the constant presence of gravity, so they also evolved in the constant presence of microbes. Consequently, nearly every aspect of human biology has evolved to deal with, and to take advantage of, the existence of associated microbiota. In some cases, the absence of a "normal microbiome" can cause disease, which can be treated by the transplant of a correct microbiome from a healthy donor. For example, fecal transplants are an effective treatment for chronic diarrhea from over abundant Clostridium difficile bacteria in the gut.

Created with PubMed® Query: "human microbiome" NOT pmcbook NOT ispreviousversion

Citations The Papers (from PubMed®)


RevDate: 2023-11-30

Landry MJ, Ward CP, Cunanan KM, et al (2023)

Cardiometabolic Effects of Omnivorous vs Vegan Diets in Identical Twins: A Randomized Clinical Trial.

JAMA network open, 6(11):e2344457 pii:2812392.

IMPORTANCE: Increasing evidence suggests that, compared with an omnivorous diet, a vegan diet confers potential cardiovascular benefits from improved diet quality (ie, higher consumption of vegetables, legumes, fruits, whole grains, nuts, and seeds).

OBJECTIVE: To compare the effects of a healthy vegan vs healthy omnivorous diet on cardiometabolic measures during an 8-week intervention.

This single-center, population-based randomized clinical trial of 22 pairs of twins (N = 44) randomized participants to a vegan or omnivorous diet (1 twin per diet). Participant enrollment began March 28, 2022, and continued through May 5, 2022. The date of final follow-up data collection was July 20, 2022. This 8-week, open-label, parallel, dietary randomized clinical trial compared the health impact of a vegan diet vs an omnivorous diet in identical twins. Primary analysis included all available data.

INTERVENTION: Twin pairs were randomized to follow a healthy vegan diet or a healthy omnivorous diet for 8 weeks. Diet-specific meals were provided via a meal delivery service from baseline through week 4, and from weeks 5 to 8 participants prepared their own diet-appropriate meals and snacks.

MAIN OUTCOMES AND MEASURES: The primary outcome was difference in low-density lipoprotein cholesterol concentration from baseline to end point (week 8). Secondary outcome measures were changes in cardiometabolic factors (plasma lipids, glucose, and insulin levels and serum trimethylamine N-oxide level), plasma vitamin B12 level, and body weight. Exploratory measures were adherence to study diets, ease or difficulty in following the diets, participant energy levels, and sense of well-being.

RESULTS: A total of 22 pairs (N = 44) of twins (34 [77.3%] female; mean [SD] age, 39.6 [12.7] years; mean [SD] body mass index, 25.9 [4.7]) were enrolled in the study. After 8 weeks, compared with twins randomized to an omnivorous diet, the twins randomized to the vegan diet experienced significant mean (SD) decreases in low-density lipoprotein cholesterol concentration (-13.9 [5.8] mg/dL; 95% CI, -25.3 to -2.4 mg/dL), fasting insulin level (-2.9 [1.3] μIU/mL; 95% CI, -5.3 to -0.4 μIU/mL), and body weight (-1.9 [0.7] kg; 95% CI, -3.3 to -0.6 kg).

CONCLUSIONS AND RELEVANCE: In this randomized clinical trial of the cardiometabolic effects of omnivorous vs vegan diets in identical twins, the healthy vegan diet led to improved cardiometabolic outcomes compared with a healthy omnivorous diet. Clinicians can consider this dietary approach as a healthy alternative for their patients.

TRIAL REGISTRATION: Identifier: NCT05297825.

RevDate: 2023-11-29

Rinaldi F, Chirico R, Trink A, et al (2023)

Resistance and Pseudo-resistance to permethrin: the importance of controlling scabies.

Frontiers in cellular and infection microbiology, 13:1297337.

RevDate: 2023-11-29

Meng D, Ai S, Spanos M, et al (2023)

Exercise and microbiome: From big data to therapy.

Computational and structural biotechnology journal, 21:5434-5445 pii:S2001-0370(23)00390-2.

Exercise is a vital component in maintaining optimal health and serves as a prospective therapeutic intervention for various diseases. The human microbiome, comprised of trillions of microorganisms, plays a crucial role in overall health. Given the advancements in microbiome research, substantial databases have been created to decipher the functionality and mechanisms of the microbiome in health and disease contexts. This review presents an initial overview of microbiomics development and related databases, followed by an in-depth description of the multi-omics technologies for microbiome. It subsequently synthesizes the research pertaining to exercise-induced modifications of the microbiome and diseases that impact the microbiome. Finally, it highlights the potential therapeutic implications of an exercise-modulated microbiome in intestinal disease, obesity and diabetes, cardiovascular disease, and immune/inflammation-related diseases.

RevDate: 2023-11-29

Kaliamoorthy S, Priya Sayeeram S, SundarRaj S, et al (2023)

Investigating the Association Between Fusobacterium nucleatum and Oral Squamous Cell Carcinoma: A Pilot Case-Control Study on Tissue Samples.

Cureus, 15(10):e47238.

Background Fusobacterium nucleatum (F. nucleatum) has been increasingly linked to oral squamous cell carcinoma (OSCC), prompting this study to explore its presence using polymerase chain reaction (PCR) and evaluate its clinical significance. Methods In this pilot case-control study, 12 OSCC tissue samples and 12 non-cancerous oral mucosal tissue samples were analyzed. Total RNA extraction and complementary DNA (cDNA) synthesis were performed using Trizol-based methods, followed by PCR amplification and gel electrophoresis. The clinical characteristics of participants and PCR results were recorded. Results Among the OSCC tissue samples, three out of 12 tested positive for F. nucleatum, while none of the control samples showed its presence. The detection rate of F. nucleatum in OSCC was 25%. Gel analysis confirmed specific amplicon amplification, and ImageJ software enabled copy number quantification. Discussion Our findings support previous research indicating a potential association between F. nucleatum and OSCC. Understanding the etiological significance of F. nucleatum in OSCC has clinical implications, including early detection, risk stratification, and prognostication. However, the limited sample size and the need for further research to elucidate underlying mechanisms are acknowledged. Conclusion This pilot study provides initial evidence of F. nucleatum's presence in a subset of OSCC samples, supporting its potential association with oral cancer. Detecting F. nucleatum in OSCC tissues holds promise for future research and clinical applications as a diagnostic and prognostic biomarker. Understanding its role in oral carcinogenesis will facilitate the development of targeted therapeutic strategies. Larger studies are warranted to validate these findings and investigate the precise mechanisms involved.

RevDate: 2023-11-29

Notaristefano G, Ponziani FR, Ranalli M, et al (2023)

Functional hypothalamic amenorrhea: gut microbiota composition and the effects of exogenous estrogen administration.

American journal of physiology. Endocrinology and metabolism [Epub ahead of print].

Functional hypothalamic amenorrhea (FHA) is characterized by estrogen deficiency that significantly impacts on metabolic, bone, cardiovascular, mental, and reproductive health. Given the importance of environmental factors such as stress, and body composition, and particularly considering the importance of estrogens in regulating the gut microbiota, some changes in the intestinal microenvironment are expected when all of these factors occur simultaneously. We aimed to assess whether the gut microbiota composition is altered in FHA and to determine the potential impact of hormonal replacement therapy (HRT) on the gut microbiota. This prospective observational study included 33 patients aged 18-34 years with FHA and 10 age-matched healthy control women. Clinical, hormonal, and metabolic evaluations were performed at baseline for the FHA group only, while gut microbiota profile was assessed by 16S rRNA gene amplicon sequencing for both groups. All measurements were repeated in patients with FHA after receiving HRT for 6 months. Gut microbiota alpha diversity at baseline was significantly different between patients with FHA and healthy controls (p<0.01). At the phylum level, the relative abundance of Fusobacteria was higher in FHA patients after HRT (p<0.01), as was that of Ruminococcus and Eubacterium at the genus level (p<0.05), which correlated with a decrease in circulating proinflammatory cytokines. FHA is a multidimensional disorder which is interconnected with dysbiosis through various mechanisms, particularly involving the gut-brain axis. HRT appears to induce a favorable shift in the gut microbiota in patients with FHA, which is also associated with a reduction in the systemic inflammatory status.

RevDate: 2023-11-29

Nguyen VH, Sharon BM, Shipman BM, et al (2023)

Complete genomes of Limosilactobacillus portuensis and Limosilactobacillus vaginalis isolated from the urine of postmenopausal women.

Microbiology resource announcements [Epub ahead of print].

There is frequent evidence that Limosilactobacillus vaginalis colonizes female genitourinary tracts but few reports of Limosilactobacillus portuensis. Their role in urinary tract infection (UTI) is unclear. We present the first complete genome of L. portuensis and a complete genome of L. vaginalis isolated from postmenopausal women with varying UTI histories.

RevDate: 2023-11-27

Moody M, R Sawyer (2023)

Is There a Community Microbial Community? A Comparison of Pathogens Between Two Hospital Surgical Intensive Care Units in a Single City.

Surgical infections [Epub ahead of print].

Background: Nosocomial and health-care-associated infections drive increased healthcare costs and negatively affect patient outcomes. The human microbiome has been heavily explored in recent years with incomplete data regarding hospital-specific and community-specific microbial communities. Although bacterial species differ between intensive care units in the same hospital, it is unclear if they differ between similar units in similar hospitals in the same community. Our hypothesis is that pathogens in surgical intensive care units (SICUs) are distinct between hospitals, even in the same community. Methods: From 2017 to 2021, data were collected prospectively from the SICUs of two 400-bed hospitals located three miles apart in the same city (Hospital A and Hospital B). Infections defined using U.S. Centers for Disease Control and Prevention (CDC) criteria were recorded for trauma and general surgery patients, as well as patient demographics, Acute Physiology and Chronic Health Evaluation (APACHE) II score, and causative organism. Results: Overall, Escherichia coli was the most commonly isolated pathogen in Hospital A, whereas Staphylococcus aureus was most commonly isolated at Hospital B. Enterococci were more common in Hospital A, and Haemophilus influenzae and Enterobacter spp. were more common in Hospital B. After stratification between trauma and non-trauma patients, however, these differences disappeared, with the exception of more overall gram-positive organisms and fewer gram-negative organisms among Hospital A trauma patients compared to Hospital B. There were no differences in rates of isolation of either fungi or resistant bacteria between hospitals. Conclusions: At a species level, admission diagnosis appears to be a greater determinant of pathogen isolation than hospital when comparing similar intensive care units (ICUs) in the same geographic area, but a larger body of data is needed to flesh out a distinct microbial map of the organisms occupying a certain geographic region. Further areas for investigation include comparison between hospital units, specific anatomic sites, and ICU versus floor patients.

RevDate: 2023-11-25

Al KF, Joris BR, Daisley BA, et al (2023)

Multi-site microbiota alteration is a hallmark of kidney stone formation.

Microbiome, 11(1):263.

BACKGROUND: Inquiry of microbiota involvement in kidney stone disease (KSD) has largely focussed on potential oxalate handling abilities by gut bacteria and the increased association with antibiotic exposure. By systematically comparing the gut, urinary, and oral microbiota of 83 stone formers (SF) and 30 healthy controls (HC), we provide a unified assessment of the bacterial contribution to KSD.

RESULTS: Amplicon and shotgun metagenomic sequencing approaches were consistent in identifying multi-site microbiota disturbances in SF relative to HC. Biomarker taxa, reduced taxonomic and functional diversity, functional replacement of core bioenergetic pathways with virulence-associated gene markers, and community network collapse defined SF, but differences between cohorts did not extend to oxalate metabolism.

CONCLUSIONS: We conclude that multi-site microbiota alteration is a hallmark of SF, and KSD treatment should consider microbial functional restoration and the avoidance of aberrant modulators such as poor diet and antibiotics where applicable to prevent stone recurrence. Video Abstract.

RevDate: 2023-11-25

Elgart M, Zhang Y, Zhang Y, et al (2023)

Anaerobic pathogens associated with OSA may contribute to pathophysiology via amino-acid depletion.

EBioMedicine, 98:104891 pii:S2352-3964(23)00457-7 [Epub ahead of print].

BACKGROUND: The human microbiome is linked to multiple metabolic disorders such as obesity and diabetes. Obstructive sleep apnoea (OSA) is a common sleep disorder with several metabolic risk factors. We investigated the associations between the gut microbiome composition and function, and measures of OSA severity in participants from a prospective community-based cohort study: the Hispanic Community Health Study/Study of Latinos (HCHS/SOL).

METHODS: Bacterial-Wide Association Analysis (BWAS) of gut microbiome measured via metagenomics with OSA measures was performed adjusting for clinical, lifestyle and co-morbidities. This was followed by functional analysis of the OSA-enriched bacteria. We utilized additional metabolomic and transcriptomic associations to suggest possible mechanisms explaining the microbiome effects on OSA.

FINDINGS: Several uncommon anaerobic human pathogens were associated with OSA severity. These belong to the Lachnospira, Actinomyces, Kingella and Eubacterium genera. Functional analysis revealed enrichment in 49 processes including many anaerobic-related ones. Severe OSA was associated with the depletion of the amino acids glycine and glutamine in the blood, yet neither diet nor gene expression revealed any changes in the production or consumption of these amino acids.

INTERPRETATION: We show anaerobic bacterial communities to be a novel component of OSA pathophysiology. These are established in the oxygen-poor environments characteristic of OSA. We hypothesize that these bacteria deplete certain amino acids required for normal human homeostasis and muscle tone, contributing to OSA phenotypes. Future work should test this hypothesis as well as consider diagnostics via anaerobic bacteria detection and possible interventions via antibiotics and amino-acid supplementation.

FUNDING: Described in methods.

RevDate: 2023-11-25

Kim J, H Koh (2023)

MiTree: A Unified Web Cloud Analytic Platform for User-Friendly and Interpretable Microbiome Data Mining Using Tree-Based Methods.

Microorganisms, 11(11): pii:microorganisms11112816.

The advent of next-generation sequencing has greatly accelerated the field of human microbiome studies. Currently, investigators are seeking, struggling and competing to find new ways to diagnose, treat and prevent human diseases through the human microbiome. Machine learning is a promising approach to help such an effort, especially due to the high complexity of microbiome data. However, many of the current machine learning algorithms are in a "black box", i.e., they are difficult to understand and interpret. In addition, clinicians, public health practitioners and biologists are not usually skilled at computer programming, and they do not always have high-end computing devices. Thus, in this study, we introduce a unified web cloud analytic platform, named MiTree, for user-friendly and interpretable microbiome data mining. MiTree employs tree-based learning methods, including decision tree, random forest and gradient boosting, that are well understood and suited to human microbiome studies. We also stress that MiTree can address both classification and regression problems through covariate-adjusted or unadjusted analysis. MiTree should serve as an easy-to-use and interpretable data mining tool for microbiome-based disease prediction modeling, and should provide new insights into microbiome-based diagnostics, treatment and prevention. MiTree is an open-source software that is available on our web server.

RevDate: 2023-11-25

Maslennikov R, Poluektova E, Zolnikova O, et al (2023)

Gut Microbiota and Bacterial Translocation in the Pathogenesis of Liver Fibrosis.

International journal of molecular sciences, 24(22): pii:ijms242216502.

Cirrhosis is the end result of liver fibrosis in chronic liver diseases. Studying the mechanisms of its development and developing measures to slow down and regress it based on this knowledge seem to be important tasks for medicine. Currently, disorders of the gut-liver axis have great importance in the pathogenesis of cirrhosis. However, gut dysbiosis, which manifests as increased proportions in the gut microbiota of Bacilli and Proteobacteria that are capable of bacterial translocation and a decreased proportion of Clostridia that strengthen the intestinal barrier, occurs even at the pre-cirrhotic stage of chronic liver disease. This leads to the development of bacterial translocation, a process by which those microbes enter the blood of the portal vein and then the liver tissue, where they activate Kupffer cells through Toll-like receptor 4. In response, the Kupffer cells produce profibrogenic cytokines, which activate hepatic stellate cells, stimulating their transformation into myofibroblasts that produce collagen and other elements of the extracellular matrix. Blocking bacterial translocation with antibiotics, probiotics, synbiotics, and other methods could slow down the progression of liver fibrosis. This was shown in a number of animal models but requires further verification in long-term randomized controlled trials with humans.

RevDate: 2023-11-25

Siebieszuk A, Sejbuk M, AM Witkowska (2023)

Studying the Human Microbiota: Advances in Understanding the Fundamentals, Origin, and Evolution of Biological Timekeeping.

International journal of molecular sciences, 24(22): pii:ijms242216169.

The recently observed circadian oscillations of the intestinal microbiota underscore the profound nature of the human-microbiome relationship and its importance for health. Together with the discovery of circadian clocks in non-photosynthetic gut bacteria and circadian rhythms in anucleated cells, these findings have indicated the possibility that virtually all microorganisms may possess functional biological clocks. However, they have also raised many essential questions concerning the fundamentals of biological timekeeping, its evolution, and its origin. This narrative review provides a comprehensive overview of the recent literature in molecular chronobiology, aiming to bring together the latest evidence on the structure and mechanisms driving microbial biological clocks while pointing to potential applications of this knowledge in medicine. Moreover, it discusses the latest hypotheses regarding the evolution of timing mechanisms and describes the functions of peroxiredoxins in cells and their contribution to the cellular clockwork. The diversity of biological clocks among various human-associated microorganisms and the role of transcriptional and post-translational timekeeping mechanisms are also addressed. Finally, recent evidence on metabolic oscillators and host-microbiome communication is presented.

RevDate: 2023-11-25

Rinaldi F, Trink A, Mondadori G, et al (2023)

The Menopausal Transition: Is the Hair Follicle "Going through Menopause"?.

Biomedicines, 11(11): pii:biomedicines11113041.

This article explores the link between menopause and changes in the hair follicle (HF) lifecycle, focusing on hormonal and metabolic dynamics. During menopause, hormonal fluctuations and aging can impact the HF, leading to phenomena such as thinning, loss of volume, and changes in hair texture. These changes are primarily attributed to a decrease in estrogen levels. However, not all women experience significant hair changes during menopause, and the extent of transformations can vary considerably from person to person, influenced by genetic factors, stress, diet, and other elements. Furthermore, menopause mirrors the aging process, affecting metabolism and blood flow to the HFs, influencing the availability of vital nutrients. The article also discusses the key role of energy metabolism in the HF lifecycle and the effect of hormones, particularly estrogens, on metabolic efficiency. The concept of a possible "menopause" clinically independent of menopause is introduced, related to changes in HF metabolism, emphasizing the importance of individual factors such as estrogen receptor responses, genetics, and last but not least, the microbiota in determining these dynamics.

RevDate: 2023-11-24

DuPont HL, MMH Salge (2023)

The Importance of a Healthy Microbiome in Pregnancy and Infancy and Microbiota Treatment to Reverse Dysbiosis for Improved Health.

Antibiotics (Basel, Switzerland), 12(11): pii:antibiotics12111617.

BACKGROUND: The microbiome of newborn infants during the first 1000 days, influenced early on by their mothers' microbiome health, mode of delivery and breast feeding, orchestrates the education and programming of the infant's immune system and determines in large part the general health of the infant for years.

METHODS: PubMed was reviewed for maternal infant microbiome health and microbiota therapy in this setting with prebiotics, probiotics, vaginal seeding and fecal microbiota transplantation (FMT).

RESULTS: A healthy nonobese mother, vaginal delivery and strict breast feeding contribute to microbiome health in a newborn and young infant. With reduced microbiome diversity (dysbiosis) during pregnancy, cesarean delivery, prematurity, and formula feeding contribute to dysbiosis in the newborn. Microbiota therapy is an important approach to repair dysbiosis in pregnant women and their infants. Currently available probiotics can have favorable metabolic effects on mothers and infants, but these effects are variable. In research settings, reversal of infant dysbiosis can be achieved via vaginal seeding or FMT. Next generation probiotics in development should replace current probiotics and FMT.

CONCLUSIONS: The most critical phase of human microbiome development is in the first 2-3 years of life. Preventing and treating dysbiosis during pregnancy and early life can have a profound effect on an infant's later health.

RevDate: 2023-11-24

Akomoneh EA, Gestels Z, Abdellati S, et al (2023)

Genome Mining Uncovers NRPS and PKS Clusters in Rothia dentocariosa with Inhibitory Activity against Neisseria Species.

Antibiotics (Basel, Switzerland), 12(11): pii:antibiotics12111592.

The growing global threat of antimicrobial resistance is reaching a crisis point as common bacterial infections, including those caused by pathogenic Neisseria species, are becoming increasingly untreatable. This is compelling the scientific community to search for new antimicrobial agents, taking advantage of computational mining and using whole genome sequences to discover natural products from the human microbiome with antibiotic effects. In this study, we investigated the crude extract from a Rothia dentocariosa strain with demonstrated antimicrobial activity against pathogenic Neisseria spp. by spot-on-lawn assay. The genomic DNA of the R. dentocariosa strain was sequenced, and bioinformatic evaluation was performed using antiSMASH and PRISM to search for biosynthetic gene clusters (BGCs). The crude extract with potential antimicrobial activity was run on Tricine-SDS-PAGE, and the putative peptides were characterised using liquid chromatography-tandem mass spectrometry (LC-MS). The crude extract inhibited the growth of the pathogenic Neisseria spp. Six BGCs were identified corresponding to non-ribosomal peptide synthases (NRPSs), polyketide synthases (PKSs), and ribosomally synthesised and post-translationally modified peptides. Three peptides were also identified corresponding to Actinorhodin polyketide putative beta-ketoacyl synthase 1. These findings serve as a useful reference to facilitate the research and development of NRPS and PKS as antimicrobial products against multidrug-resistant N. gonorrhoeae.

RevDate: 2023-11-24

Kumavath R, Pavithran H, Paul S, et al (2024)

Effects of gut microbiome and obesity on the development, progression and prevention of cancer (Review).

International journal of oncology, 64(1):.

Cancer is one of the leading causes of death worldwide and it is estimated that the mortality rate of cancer will increase in the coming years. The etiology of the development and progression of cancer is multifactorial. Insights have been gained on the association between the human microbiome and tumor cell malignancy. A number of commensal microbe species are present in the human gut. They serve pivotal roles in maintaining several health and disease conditions, such as inflammatory bowel disease, irritable bowel syndrome, obesity and diabetes. Known major factors involved in cancer development include age, hormone levels, alcohol consumption, diet, being overweight, obesity, and infections, regardless of the type of cancer. Therefore, the present review aims to discuss the relationship between the gut microbiome and obesity‑associated malignancies, including colorectal, gastric and liver cancer. Obesity has been reported to contribute to the development of numerous types of cancer primarily caused by high fatty food intake. In addition, obesity‑associated microbiome alterations can lead to cancer and its progression. Dysbiosis of the gut microbiota can alter the metabolite profile, whilst increasing the levels of toxins, such as Bacteroides fragilis toxin and colibactin and cytolethal distending toxin, which are responsible for oncogenesis. The present review provides insights into the impact of gut microbiome dysbiosis on the progression of different types of cancers associated with obesity. It also discusses possible strategies for preserving a healthy gut microbiome. Different pre‑clinical and clinical models are available for studying cancer development downstream of gut microbiome dysbiosis. Furthermore, the role of metabolites or drugs employed in colorectal, gastric and liver cancer therapy would be discussed.

RevDate: 2023-11-24

Akbari E, Milani A, Seyedinkhorasani M, et al (2023)

HPV co-infections with other pathogens in cancer development: A comprehensive review.

Journal of medical virology, 95(11):e29236.

High-risk human papillomaviruses (HR-HPVs) cause various malignancies in the anogenital and oropharyngeal regions. About 70% of cervical and oropharyngeal cancers are caused by HPV types 16 and 18. Notably, some viruses including herpes simplex virus, Epstein-Barr virus, and human immunodeficiency virus along with various bacteria often interact with HPV, potentially impacting its replication, persistence, and cancer progression. Thus, HPV infection can be significantly influenced by co-infecting agents that influence infection dynamics and disease progression. Bacterial co-infections (e.g., Chlamydia trachomatis) along with bacterial vaginosis-related species also interact with HPV in genital tract leading to viral persistence and disease outcomes. Co-infections involving HPV and diverse infectious agents have significant implications for disease transmission and clinical progression. This review explores multiple facets of HPV infection encompassing the co-infection dynamics with other pathogens, interaction with the human microbiome, and its role in disease development.

RevDate: 2023-11-23

Bonnici V, Mengoni C, Mangoni M, et al (2023)

PanDelos-frags: A methodology for discovering pangenomic content of incomplete microbial assemblies.

Journal of biomedical informatics pii:S1532-0464(23)00273-3 [Epub ahead of print].

Pangenomics was originally defined as the problem of comparing the composition of genes into gene families within a set of bacterial isolates belonging to the same species. The problem requires the calculation of sequence homology among such genes. When combined with metagenomics, namely for human microbiome composition analysis, gene-oriented pangenome detection becomes a promising method to decipher ecosystem functions and population-level evolution. Established computational tools are able to investigate the genetic content of isolates for which a complete genomic sequence is available. However, there is a plethora of incomplete genomes that are available on public resources, which only a few tools may analyze. Incomplete means that the process for reconstructing their genomic sequence is not complete, and only fragments of their sequence are currently available. However, the information contained in these fragments may play an essential role in the analyses. Here, we present PanDelos-frags, a computational tool which exploits and extends previous results in analysing complete genomes. It provides a new methodology for inferring missing genetic information and thus for managing incomplete genomes. PanDelos-frags outperforms state-of-the-art approaches in reconstructing gene families in synthetic benchmarks and in a real use case of metagenomics. PanDelos-frags is publicly available at

RevDate: 2023-11-23

Donato K, Donato K, Bonetti G, et al (2023)

Exploring the Impact of Tobacco Usage on Microbiome Dysbiosis and Associated Health Risks: A Comprehensive Review of Recent Advancements and Future Directions.

La Clinica terapeutica, 174(Suppl 2(6)):119-125.

All over the world, tobacco usage is quickly expanding. Though it presents a major health risk and is anticipated to have long-lasting impacts on the public and economic health of the country, its consumers are increasing with every passing day. Tobacco is being used in a variety of ways, with cigarettes being the most popular. Smoking affects the healthy oral, intestinal, and pulmonary microbiomes, often altering the dynamic equilibrium of the diverse bacteria that make up the human microbiome, or "dysbiosis". Smoking-induced dysbiosis can lead to developing conditions like asthma, chronic obstructive pul-monary disease, Crohn's disease, ulcerative colitis, and periodontitis. The purpose of the following article is to provide a better and more comprehensive overview of the key areas that the tobacco industry needs to investigate, such as microbiome manipulation, to provide a complete picture of recent advancements in tobacco research while also keeping public safety in mind, and the various diseases linked to tobacco use.

RevDate: 2023-11-23

Hirsch P, Tagirdzhanov A, Kushnareva A, et al (2023)

ABC-HuMi: the Atlas of Biosynthetic Gene Clusters in the Human Microbiome.

Nucleic acids research pii:7442531 [Epub ahead of print].

The human microbiome has emerged as a rich source of diverse and bioactive natural products, harboring immense potential for therapeutic applications. To facilitate systematic exploration and analysis of its biosynthetic landscape, we present ABC-HuMi: the Atlas of Biosynthetic Gene Clusters (BGCs) in the Human Microbiome. ABC-HuMi integrates data from major human microbiome sequence databases and provides an expansive repository of BGCs compared to the limited coverage offered by existing resources. Employing state-of-the-art BGC prediction and analysis tools, our database ensures accurate annotation and enhanced prediction capabilities. ABC-HuMi empowers researchers with advanced browsing, filtering, and search functionality, enabling efficient exploration of the resource. At present, ABC-HuMi boasts a catalog of 19 218 representative BGCs derived from the human gut, oral, skin, respiratory and urogenital systems. By capturing the intricate biosynthetic potential across diverse human body sites, our database fosters profound insights into the molecular repertoire encoded within the human microbiome and offers a comprehensive resource for the discovery and characterization of novel bioactive compounds. The database is freely accessible at

RevDate: 2023-11-21

Wang SH, Zheng T, NL Fawzi (2023)

Structure and position-specific interactions of prion-like domains in transcription factor Efg1 phase separation.

bioRxiv : the preprint server for biology pii:2023.11.09.566450.

UNLABELLED: Candida albicans , a prominent member of the human microbiome, can make an opportunistic switch from commensal coexistence to pathogenicity accompanied by an epigenetic shift between the white and opaque cell states. This transcriptional switch is under precise regulation by a set of transcription factors (TFs), with Enhanced Filamentous Growth Protein 1 (Efg1) playing a central role. Previous research has emphasized the importance of Egf1's prion-like domain (PrLD) and the protein's ability to undergo phase separation for the white-to-opaque transition of C. albicans . However, the underlying molecular mechanisms of Efg1 phase separation have remained underexplored. In this study, we delved into the biophysical basis of Efg1 phase separation, revealing the significant contribution of both N-terminal (N) and C-terminal (C) PrLDs. Through NMR structural analysis, we found that Efg1 N-PrLD and C-PrLD are mostly disordered though have prominent partial α-helical secondary structures in both domains. NMR titration experiments suggest that the partially helical structures in N-PrLD act as hubs for self-interaction as well as Efg1 interaction with RNA. Using condensed-phase NMR spectroscopy, we uncovered diverse amino acid interactions underlying Efg1 phase separation. Particularly, we highlight the indispensable role of tyrosine residues within the transient α-helical structures of PrLDs particularly in the N-PrLD compared to the C-PrLD in stabilizing phase separation. Our study provides evidence that the transient α-helical structure is present in the phase separated state and highlights the particular importance of aromatic residues within these structures for phase separation. Together, these results enhance the understanding of C. albicans TF interactions that lead to virulence and provide a crucial foundation for potential antifungal therapies targeting the transcriptional switch.

STATEMENT OF SIGNIFICANCE: Phase separated condensates have been found across the domains of life and many types of cells. To understand their varied functions, seeing the residue-by-residue details of the structure and interactions of component protein constituents is essential. A set of transcription factors that phase-separate controls cell fate of the pathogenic yeast Candida albicans. Here, we examine the structural and interaction details of a main regulator of this process, Efg1, using NMR spectroscopy and biochemical assays. We find Efg1's phase-separating domains are not entirely disordered as often assumed but in fact contain helical regions that persist upon phase separation. We also reveal the balance of contacts formed in the condensed phase and the importance of specific residues and regions in phase separation.

RevDate: 2023-11-18

Cohen DG, RA Wingert (2023)

Forever young by Alpha(diversity)ville: restricting intestinal microbiome maturation stunts immune system development and increases susceptibility to infection.

Tissue barriers [Epub ahead of print].

The microbiome is a keystone of adult gastrointestinal (GI) tract health, where it facilitates digestion, wards off pathogen colonization, and exerts a powerful influence on the physiological health of organs ranging from the brain to the kidneys. From its establishment at birth and through the initial years of childhood, the human microbiome is particularly dynamic, shifting in its composition and alpha (species) diversity to an adult profile as dietary sustenance transitions from milk-based sources to others such as solid food. An innovative study has now demonstrated how microbiome maturation is requisite both for the progression of immune system development and for long-term gut barrier function. These insights have significant ramifications for designing pediatric approaches to cultivate immune cell ontogeny in the formative stages of human infancy.

RevDate: 2023-11-18

Garba Z, Bonkoungou IOJ, Millogo NO, et al (2023)

Wastewater from healthcare centers in Burkina Faso is a source of ESBL, AmpC-β-lactamase and carbapenemase-producing Escherichia coli and Klebsiella pneumoniae.

BMC microbiology, 23(1):351.

BACKGROUND: Extended-spectrum β-lactamase (ESBL), plasmid-mediated AmpC-β-lactamase and carbapenemase-producing Escherichia coli and Klebsiella pneumoniae have spread into the environment worldwide posing a potential public health threat. However, the prevalence data for low- and middle-income countries are still scarce. The aim of this study was to evaluate the presence of ESBL, AmpC-β-lactamase and carbapenemase-producing and multidrug-resistant E. coli and K. pneumoniae in wastewaters from healthcare centers in Burkina Faso.

RESULTS: Eighty-four (84) wastewater samples were collected from five healthcare centers and plated on selective ESBL ChromAgar. E. coli and Klebsiella pneumoniae isolates were identified using API20E. ESBL-producing bacteria were detected in 97.6% of the samples and their average concentration per hospital ranged from 1.10 × 10[5] to 5.23 × 10[6] CFU/mL. Out of 170 putative ESBL-producing isolates (64% of them were E. coli) and 51 putative AmpC-β-lactamase-producing isolates, 95% and 45% were confirmed, respectively. Carbapenemase production was detected in 10 isolates, of which 6 were NDM producers, 3 were OXA-48 producers and 1 was NDM and OXA-48 producer. All isolates were multidrug resistant and, moreover, all of them were resistant to all tested β-lactams. Resistance to ESBL inhibitors was also common, up to 66% in E. coli and 62% in K. pneumoniae. Amikacin, fosfomycin and nitrofurantoin were the antibiotics to which the least resistance was detected.

CONCLUSIONS: This study showed that wastewater from healthcare centers constitutes a reservoir of multidrug-resistant bacteria in Burkina Faso, including carbapenemase producers. Untreated healthcare wastewater entering the environment exposes people and animals to infections caused by these multi-resistant bacteria, which are difficult to treat, especially in the resource-poor settings.

RevDate: 2023-11-17

King AM, Zhang Z, Glassey E, et al (2023)

Systematic mining of the human microbiome identifies antimicrobial peptides with diverse activity spectra.

Nature microbiology [Epub ahead of print].

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.

RevDate: 2023-11-16

Azamfirei L (2023)

The Human Microbiome in Intensive Care - A Journey Forward?.

Journal of critical care medicine (Universitatea de Medicina si Farmacie din Targu-Mures), 9(4):205-207 pii:jccm-2023-0032.

RevDate: 2023-11-15

Asnicar F, Thomas AM, Passerini A, et al (2023)

Machine learning for microbiologists.

Nature reviews. Microbiology [Epub ahead of print].

Machine learning is increasingly important in microbiology where it is used for tasks such as predicting antibiotic resistance and associating human microbiome features with complex host diseases. The applications in microbiology are quickly expanding and the machine learning tools frequently used in basic and clinical research range from classification and regression to clustering and dimensionality reduction. In this Review, we examine the main machine learning concepts, tasks and applications that are relevant for experimental and clinical microbiologists. We provide the minimal toolbox for a microbiologist to be able to understand, interpret and use machine learning in their experimental and translational activities.

RevDate: 2023-11-15

Piazzesi A, Pane S, Russo A, et al (2023)

Case Report: The impact of severe cryptosporidiosis on the gut microbiota of a pediatric patient with CD40L immunodeficiency.

Frontiers in cellular and infection microbiology, 13:1281440.

Cryptosporidium parvum is a protozoan parasite and one of the leading causes of gastroenteritis in the world, primarily affecting very young children and immunocompromised patients. While infection is usually self-limiting, it can become chronic and even lethal in these vulnerable populations, in whom Cryptosporidium treatments are generally ineffective, due to their acting in concert with a functioning immune system. Here, we describe a case of chronic cryptosporidiosis in a European child with severe CD40L immunodeficiency infected with Cryptosporidium parvum of the IIa20G1 subgenotype, a lineage which has thus far only ever been described in the Middle East. After years of on-off treatment with conventional and non-conventional anti-parasitic drugs failed to clear parasitosis, we performed targeted metagenomics to observe the bacterial composition of the patient's gut microbiota (GM), and to evaluate fecal microbiota transplantation (FMT) as a potential treatment option. We found that C. parvum infection led to significant shifts in GM bacterial composition in our patient, with consequent shifts in predicted intestinal functional signatures consistent with a state of persistent inflammation. This, combined with the patient's poor prognosis and increasing parasitic burden despite many rounds of anti-parasitic drug treatments, made the patient a potential candidate for an experimental FMT procedure. Unfortunately, given the many comorbidities that were precipitated by the patient's immunodeficiency and chronic C. parvum infection, FMT was postponed in favor of more urgently necessary liver and bone marrow transplants. Tragically, after the first liver transplant failed, the patient lost his life before undergoing FMT and a second liver transplant. With this case report, we present the first description of how cryptosporidiosis can shape the gut microbiota of a pediatric patient with severe immunodeficiency. Finally, we discuss how both our results and the current scientific literature suggest that GM modulations, either by probiotics or FMT, can become novel treatment options for chronic Cryptosporidium infection and its consequent complications, especially in those patients who do not respond to the currently available anti-parasitic therapies.

RevDate: 2023-11-14

Walker AC, Bhargava R, Bucher M, et al (2023)

Identification of proteotoxic and proteoprotective bacteria that non-specifically affect proteins associated with neurodegenerative diseases.

bioRxiv : the preprint server for biology pii:2023.10.24.563685.

Neurodegenerative protein conformational diseases (PCDs), such as Alzheimer's, Parkinson's, and Huntington's, are a leading cause of death and disability worldwide and have no known cures or effective treatments. Emerging evidence suggests a role for the gut microbiota in the pathogenesis of neurodegenerative PCDs; however, the influence of specific bacteria on the culprit proteins associated with each of these diseases remains elusive, primarily due to the complexity of the microbiota. In the present study, we employed a single-strain screening approach to identify human bacterial isolates that enhance or suppress the aggregation of culprit proteins and the associated toxicity in Caenorhabditis elegans expressing Aβ 1-42 , α-synuclein, and polyglutamine tracts. Here, we reveal the first comprehensive analysis of the human microbiome for its effect on proteins associated with neurodegenerative diseases. Our results suggest that bacteria affect the aggregation of metastable proteins by modulating host proteostasis rather than selectively targeting specific disease-associated proteins. These results reveal bacteria that potentially influence the pathogenesis of PCDs and open new promising prevention and treatment opportunities by altering the abundance of beneficial and detrimental microbes.

RevDate: 2023-11-14

Mäenpää K, Ilves M, Zhao L, et al (2023)

Effects of Superficial Scratching and Engineered Nanomaterials on Skin Gene Profiles and Microbiota in SKH-1 Mice.

International journal of molecular sciences, 24(21): pii:ijms242115629.

Scratching damages upper layers of the skin, breaks this first line of immune defence, and leads to inflammation response, which often also modifies the microbiota of the skin. Although the healing of incision wounds is well-described, there are fewer studies on superficial wounds. We used a simulated model of skin scratching to study changes in the host transcriptome, skin microbiota, and their relationship. Additionally, we examined the effect of nanosized ZnO, TiO2, and Ag on both intact and damaged skin. At 24 h after exposure, the number of neutrophils was increased, 396 genes were differentially expressed, and microbiota compositions changed between scratched and intact control skin. At 7 d, the skin was still colonised by gut-associated microbes, including Lachnospiraceae, present in the cage environment, while the transcriptomic responses decreased. To sum up, the nanomaterial exposures reduced the relative abundance of cutaneous microbes on healthy skin, but the effect of scratching was more significant for the transcriptome than the nanomaterial exposure both at 24 h and 7 d. We conclude that superficial skin scratching induces inflammatory cell accumulation and changes in gene expression especially at 24 h, while the changes in the microbiota last at least 7 days.

RevDate: 2023-11-11

Smajdor J, Jedlińska K, Porada R, et al (2023)

The impact of gut bacteria producing long chain homologs of vitamin K2 on colorectal carcinogenesis.

Cancer cell international, 23(1):268.

Colorectal cancer (CRC) is one of the foremost causes of cancer-related deaths. Lately, a close connection between the course of CRC and the intestinal microbiota has been revealed. Vitamin K2 (VK2) is a bacterially derived compound that plays a crucial role in the human body. Its significant anti-cancer properties may result, inter alia, from a quinone ring possessing a specific chemical structure found in many chemotherapeutics. VK2 can be supplied to our body exogenously, i.e., through dietary supplements or fermented food (e.g., yellow cheese, fermented soybeans -Natto), and endogenously, i.e., through the production of bacteria that constantly colonize the human microbiome of the large intestine.This paper focuses on endogenous K2 synthesized by the most active members of the human gut microbiome. This analysis tested 86 intestinally derived bacterial strains, among which the largest VK2 producers (Lactobacillus, Bifidobacterium, Bacillus) were selected. Moreover, based on the chosen VK2-MK4 homolog, the potential of VK2 penetration into Caco-2 cells in an aqueous environment without the coexistence of fats, pancreatic enzymes, or bile salts has been displayed. The influence of three VK2 homologs: VK2-MK4, VK2-MK7 and VK2-MK9 on apoptosis and necrosis of Caco-2 cells was tested proving the lack of their harmful effects on the tested cells. Moreover, the unique role of long-chain homologs (VK2-MK9 and VK2-MK7) in inhibiting the secretion of pro-inflammatory cytokines such as IL-8 (for Caco-2 tissue) and IL-6 and TNFα (for RAW 264.7) has been documented.

RevDate: 2023-11-11

Zhou X, You L, Xin Z, et al (2023)

Leveraging circulating microbiome signatures to predict tumor immune microenvironment and prognosis of patients with non-small cell lung cancer.

Journal of translational medicine, 21(1):800.

BACKGROUND: Accumulating evidence supports the significant role of human microbiome in development and therapeutic response of tumors. Circulating microbial DNA is non-invasive and could show a general view of the microbiome of host, making it a promising biomarker for cancers. However, whether circulating microbiome is associated with prognosis of non-small cell lung cancer (NSCLC) and its potential mechanisms on tumor immune microenvironment still remains unknown.

METHODS: The blood microbiome data and matching tumor RNA-seq data of TCGA NSCLC patients were obtained from Poore's study and UCSC Xena. Univariate and multivariate Cox regression analysis were used to identify circulating microbiome signatures associated with overall survival (OS) and construct the circulating microbial abundance prognostic scoring (MAPS) model. Nomograms integrating clinical characteristics and circulating MAPS scores were established to predict OS rate of NSCLC patients. Joint analysis of blood microbiome data and matching tumor RNA-seq data was used to deciphered the tumor microenvironment landscape of patients in circulating MAPS-high and MAPS-low groups. Finally, the predictive value of circulating MAPS on the efficacy of immunotherapy and chemotherapy were assessed.

RESULTS: A circulating MAPS prediction model consisting of 14 circulating microbes was constructed and had an independent prognostic value for NSCLC. The integration of circulating MAPS into nomograms may improve the prognosis predictive power. Joint analysis revealed potential interactions between prognostic circulating microbiome and tumor immune microenvironment. Especially, intratumor plasma cells and humoral immune response were enriched in circulating MAPS-low group, while intratumor CD4 + Th2 cells and proliferative related pathways were enriched in MAPS-high group. Finally, drug sensitivity analysis indicated the potential of circulating MAPS as a predictor of chemotherapy efficacy.

CONCLUSION: A circulating MAPS prediction model was constructed successfully and showed great prognostic value for NSCLC. Our study provides new insights of interactions between microbes, tumors and immunity, and may further contribute to precision medicine for NSCLC.

RevDate: 2023-11-10
CmpDate: 2023-11-10

Blumberg K, Miller M, Ponsero A, et al (2022)

Ontology-driven analysis of marine metagenomics: what more can we learn from our data?.

GigaScience, 12:.

BACKGROUND: The proliferation of metagenomic sequencing technologies has enabled novel insights into the functional genomic potentials and taxonomic structure of microbial communities. However, cyberinfrastructure efforts to manage and enable the reproducible analysis of sequence data have not kept pace. Thus, there is increasing recognition of the need to make metagenomic data discoverable within machine-searchable frameworks compliant with the FAIR (Findability, Accessibility, Interoperability, and Reusability) principles for data stewardship. Although a variety of metagenomic web services exist, none currently leverage the hierarchically structured terminology encoded within common life science ontologies to programmatically discover data.

RESULTS: Here, we integrate large-scale marine metagenomic datasets with community-driven life science ontologies into a novel FAIR web service. This approach enables the retrieval of data discovered by intersecting the knowledge represented within ontologies against the functional genomic potential and taxonomic structure computed from marine sequencing data. Our findings highlight various microbial functional and taxonomic patterns relevant to the ecology of prokaryotes in various aquatic environments.

CONCLUSIONS: In this work, we present and evaluate a novel Semantic Web architecture that can be used to ask novel biological questions of existing marine metagenomic datasets. Finally, the FAIR ontology searchable data products provided by our API can be leveraged by future research efforts.

RevDate: 2023-11-06

Yi X, Lu H, Liu X, et al (2023)

Unravelling the enigma of the human microbiome: Evolution and selection of sequencing technologies.

Microbial biotechnology [Epub ahead of print].

The human microbiome plays a crucial role in maintaining health, with advances in high-throughput sequencing technology and reduced sequencing costs triggering a surge in microbiome research. Microbiome studies generally incorporate five key phases: design, sampling, sequencing, analysis, and reporting, with sequencing strategy being a crucial step offering numerous options. Present mainstream sequencing strategies include Amplicon sequencing, Metagenomic Next-Generation Sequencing (mNGS), and Targeted Next-Generation Sequencing (tNGS). Two innovative technologies recently emerged, namely MobiMicrobe high-throughput microbial single-cell genome sequencing technology and 2bRAD-M simplified metagenomic sequencing technology, compensate for the limitations of mainstream technologies, each boasting unique core strengths. This paper reviews the basic principles and processes of these three mainstream and two novel microbiological technologies, aiding readers in understanding the benefits and drawbacks of different technologies, thereby guiding the selection of the most suitable method for their research endeavours.

RevDate: 2023-11-08
CmpDate: 2023-11-06

Marzano V, Levi Mortera S, Vernocchi P, et al (2023)

Williams-Beuren syndrome shapes the gut microbiota metaproteome.

Scientific reports, 13(1):18963.

Williams-Beuren syndrome (WBS) is a rare genetic neurodevelopmental disorder with multi-systemic manifestations. The evidence that most subjects with WBS face gastrointestinal (GI) comorbidities, have prompted us to carry out a metaproteomic investigation of their gut microbiota (GM) profile compared to age-matched healthy subjects (CTRLs). Metaproteomic analysis was carried out on fecal samples collected from 41 individuals with WBS, and compared with samples from 45 CTRLs. Stool were extracted for high yield in bacterial protein group (PG) content, trypsin-digested and analysed by nanoLiquid Chromatography-Mass Spectrometry. Label free quantification, taxonomic assignment by the lowest common ancestor (LCA) algorithm and functional annotations by COG and KEGG databases were performed. Data were statistically interpreted by multivariate and univariate analyses. A WBS GM functional dissimilarity respect to CTRLs, regardless age distribution, was reported. The alterations in function of WBSs GM was primarily based on bacterial pathways linked to carbohydrate transport and metabolism and energy production. Influence of diet, obesity, and GI symptoms was assessed, highlighting changes in GM biochemical patterns, according to WBS subsets' stratification. The LCA-derived ecology unveiled WBS-related functionally active bacterial signatures: Bacteroidetes related to over-expressed PGs, and Firmicutes, specifically the specie Faecalibacterium prausnitzii, linked to under-expressed PGs, suggesting a depletion of beneficial bacteria. These new evidences on WBS gut dysbiosis may offer novel targets for tailored interventions.

RevDate: 2023-11-04

Routy B, Lenehan JG, Miller WH, et al (2023)

Author Correction: Fecal microbiota transplantation plus anti-PD-1 immunotherapy in advanced melanoma: a phase I trial.

RevDate: 2023-11-03

Qiao X, He H, Sun L, et al (2023)

Testing latent classes in gut microbiome data using generalized Poisson regression models.

Statistics in medicine [Epub ahead of print].

Human microbiome research has gained increasing importance due to its critical roles in comprehending human health and disease. Within the realm of microbiome research, the data generated often involves operational taxonomic unit counts, which can frequently present challenges such as over-dispersion and zero-inflation. To address dispersion-related concerns, the generalized Poisson model offers a flexible solution, effectively handling data characterized by over-dispersion, equi-dispersion, and under-dispersion. Furthermore, the realm of zero-inflated generalized Poisson models provides a strategic avenue to simultaneously tackle both over-dispersion and zero-inflation. The phenomenon of zero-inflation frequently stems from the heterogeneous nature of study populations. It emerges when specific microbial taxa fail to thrive in the microbial community of certain subjects, consequently resulting in a consistent count of zeros for these individuals. This subset of subjects represents a latent class, where their zeros originate from the genuine absence of the microbial taxa. In this paper, we introduce a novel testing methodology designed to uncover such latent classes within generalized Poisson regression models. We establish a closed-form test statistic and deduce its asymptotic distribution based on estimating equations. To assess its efficacy, we conduct an extensive array of simulation studies, and further apply the test to detect latent classes in human gut microbiome data from the Bogalusa Heart Study.

RevDate: 2023-11-02

Thomas SC, Miller G, Li X, et al (2023)

Getting off tract: contributions of intraorgan microbiota to cancer in extraintestinal organs.

Gut pii:gutjnl-2022-328834 [Epub ahead of print].

The gastrointestinal ecosystem has received the most attention when examining the contributions of the human microbiome to health and disease. This concentration of effort is logical due to the overwhelming abundance of microbes in the gut coupled with the relative ease of sampling compared with other organs. However, the intestines are intimately connected to multiple extraintestinal organs, providing an opportunity for homeostatic microbial colonisation and pathogenesis in organs traditionally thought to be sterile or only transiently harbouring microbiota. These habitats are challenging to sample, and their low microbial biomass among large amounts of host tissue can make study challenging. Nevertheless, recent findings have shown that many extraintestinal organs that are intimately linked to the gut harbour stable microbiomes, which are colonised from the gut in selective manners and have highlighted not just the influence of the bacteriome but that of the mycobiome and virome on oncogenesis and health.

RevDate: 2023-11-02

Celoria V, Rosset F, Pala V, et al (2023)

The Skin Microbiome and Its Role in Psoriasis: A Review.

Psoriasis (Auckland, N.Z.), 13:71-78.

The skin microbiome is made of various microorganisms, most of which have the function of protecting individuals from harmful pathogens, and they are involved in innate and adaptive immune responses. The skin acts as a physical and immunological barrier against external stimuli, including pathogens and physical damage. Changes in the composition of the skin microbiome can trigger inflammatory processes leading to inflammatory skin diseases in susceptible individuals. Psoriasis (PsO) is a chronic inflammatory disease with a multifactorial etiology, where breakdown of immune tolerance to cutaneous microorganisms is implicated in its pathogenesis. Dysregulation of the microbiome due to genetic and environmental factors plays a significant role in the development of psoriatic disease. Dermatologic conditions such as atopic dermatitis, acne, psoriasis, and rosacea have been associated with intestinal dysbiosis. The skin microbiota composition is crucial for the development of appropriate immune responses, and alterations in the skin microbiome can contribute to changes in physiology and susceptibility to skin diseases or inflammatory conditions. Understanding the microbial settlement of the skin and the network of interactions that occur throughout life is essential for comprehending the pathogenesis of skin diseases and developing innovative treatments. With this article we tried to explore the relationship between the human microbiome and psoriatic disease, shedding light on the functions of the microbiome and the inflammatory disease processes to identify additional therapeutic targets. This review aims to highlight the relationship between skin and gut microbiome functions and inflammatory processes in skin psoriasis and psoriatic arthritis (PsA). The goal is to facilitate future studies on the skin microbiome to identify potential novel therapies for patients with psoriatic disease.

RevDate: 2023-10-31

Hussein N, Rajasuriar R, Khan AM, et al (2023)

The role of the gut microbiome in hematological cancers.

Molecular cancer research : MCR pii:729918 [Epub ahead of print].

Humans are in a complex symbiotic relationship with a wide range of microbial organisms, including bacteria, viruses, and fungi. The evolution and composition of the human microbiome indicate how it may affect human health and disease susceptibility. Microbiome alteration, termed as dysbiosis, has been linked to the pathogenesis and progression of haematological cancers. A variety of mechanisms, including epithelial barrier disruption, local chronic inflammation response triggering, antigen dis-sequestration, and molecular mimicry have been proposed to be associated with gut microbiota. Dysbiosis may be induced or worsened by cancer therapies (such as chemotherapy and/or haematopoietic stem cell transplantation) or infection. The use of antibiotics during treatment may also promote dysbiosis, with possible long-term consequences. The aim of this review is to provide a succinct summary of the current knowledge describing the role of the microbiome in haematological cancers, as well as its influence on their therapies. Modulation of the gut microbiome, involving modifying beneficial microorganisms in the management and treatment of haematological cancers is also discussed. Furthermore, the latest developments on modelling approaches and tools used for computational analyses of the gut microbiome data are included to aid better understanding in interpretation of information.

RevDate: 2023-10-31

Mishra AK, Mahmud I, Lorenzi PL, et al (2023)

TARO: tree-aggregated factor regression for microbiome data integration.

bioRxiv : the preprint server for biology pii:2023.10.17.562792.

MOTIVATION: Although the human microbiome plays a key role in health and disease, the biological mechanisms underlying the interaction between the microbiome and its host are incompletely understood. Integration with other molecular profiling data offers an opportunity to characterize the role of the microbiome and elucidate therapeutic targets. However, this remains challenging to the high dimensionality, compositionality, and rare features found in microbiome profiling data. These challenges necessitate the use of methods that can achieve structured sparsity in learning cross-platform association patterns.

RESULTS: We propose Tree-Aggregated factor RegressiOn (TARO) for the integration of microbiome and metabolomic data. We leverage information on the phylogenetic tree structure to flexibly aggregate rare features. We demonstrate through simulation studies that TARO accurately recovers a low-rank coefficient matrix and identifies relevant features. We applied TARO to microbiome and metabolomic profiles gathered from subjects being screened for colorectal cancer to understand how gut microrganisms shape intestinal metabolite abundances.

The R package TARO implementing the proposed methods is available online at .

RevDate: 2023-10-30

Vata D, Tarcau BM, Popescu IA, et al (2023)

Update on Obesity in Psoriasis Patients.

Life (Basel, Switzerland), 13(10):.

Psoriasis is a chronic inflammatory skin condition, with genetic, epigenetic, environmental, and lifestyle factors contributing to its onset and recurrence. Severe psoriasis has a great impact on quality of life, which is similar to that of insulin-dependent diabetes, depression, and ischemic heart disease, but with a lower mortality. There is an overlap between the rising incidences of autoimmune diseases and obesity. In recent years, research has shown that there is an association between psoriasis and obesity. Psoriasis is linked to obesity in a two-way manner, as each can precipitate the development of the other. Several adipose tissue-secreted adipokines were shown to be elevated in obese psoriasis patients, exhibiting similar mechanisms of action to those underlying the pathogenesis of psoriasis. Excess body weight can influence not only the treatment response in psoriasis, but also the adverse events, leading to decreased patient compliance. Specific human microbiome patterns have been identified for obesity and psoriasis and could represent a future therapeutic target in selected individuals.

RevDate: 2023-11-06
CmpDate: 2023-10-30

Aboushaala K, Wong AYL, Barajas JN, et al (2023)

The Human Microbiome and Its Role in Musculoskeletal Disorders.

Genes, 14(10):.

Musculoskeletal diseases (MSDs) are characterized as injuries and illnesses that affect the musculoskeletal system. MSDs affect every population worldwide and are associated with substantial global burden. Variations in the makeup of the gut microbiota may be related to chronic MSDs. There is growing interest in exploring potential connections between chronic MSDs and variations in the composition of gut microbiota. The human microbiota is a complex community consisting of viruses, archaea, bacteria, and eukaryotes, both inside and outside of the human body. These microorganisms play crucial roles in influencing human physiology, impacting metabolic and immunological systems in health and disease. Different body areas host specific types of microorganisms, with facultative anaerobes dominating the gastrointestinal tract (able to thrive with or without oxygen), while strict aerobes prevail in the nasal cavity, respiratory tract, and skin surfaces (requiring oxygen for development). Together with the immune system, these bacteria have coevolved throughout time, forming complex biological relationships. Changes in the microbial ecology of the gut may have a big impact on health and can help illnesses develop. These changes are frequently impacted by lifestyle choices and underlying medical disorders. The potential for safety, expenses, and efficacy of microbiota-based medicines, even with occasional delivery, has attracted interest. They are, therefore, a desirable candidate for treating MSDs that are chronic and that may have variable progression patterns. As such, the following is a narrative review to address the role of the human microbiome as it relates to MSDs.

RevDate: 2023-10-30

Ye C, Dong C, Lin Y, et al (2023)

Interplay between the Human Microbiome and Biliary Tract Cancer: Implications for Pathogenesis and Therapy.

Microorganisms, 11(10):.

Biliary tract cancer, encompassing intrahepatic and extrahepatic cholangiocarcinoma as well as gallbladder carcinoma, stands as a prevalent malignancy characterized by escalating incidence rates and unfavorable prognoses. The onset of cholangiocarcinoma involves a multitude of risk factors and could potentially be influenced by microbial exposure. The human microbiome, encompassing the entirety of human microbial genetic information, assumes a pivotal role in regulating key aspects such as host digestion, absorption, immune responses, and metabolism. The widespread application of next-generation sequencing technology has notably propelled investigations into the intricate relationship between the microbiome and diseases. An accumulating body of evidence strongly suggests a profound interconnection between biliary tract cancer and the human microbiome. This article critically appraises the existing evidence pertaining to the microbiome milieu within patients afflicted by biliary tract cancer. Furthermore, it delves into potential mechanisms through which dysregulation of the human microbiome could contribute to the advancement of biliary tract cancer. Additionally, the article expounds on its role in the context of chemotherapy and immunotherapy for biliary tract cancer.

RevDate: 2023-10-30

Lopetuso LR, Laterza L, Petito V, et al (2023)

Serial Fecal Microbiota Infusions via Colonoscopy for Active Ulcerative Colitis: A Feasibility, Safety, and Translational Monocentric Italian Study.

Microorganisms, 11(10):.

The effectiveness of fecal microbiota transplantation (FMT) in ulcerative colitis (UC) remains unclear. This study aimed to investigate the feasibility and effectiveness of serial fecal infusions via colonoscopy in patients with active UC. Subjects with mild-to-moderate UC received three consecutive fecal infusions via colonoscopy. A control population with the same baseline features receiving Infliximab treatment was enrolled. Adverse events and clinical, endoscopic, and microbial outcomes were investigated. Nineteen patients with mildly-to-moderately active UC were enrolled. Clinical response was obtained in six patients at week 2, in eight at week 6, and in nine at week 12. Clinical response was maintained in eight patients at week 24. Endoscopic remission at week 12 was reached in six patients. In the control population, 13/19 patients achieved clinical response at week 6, and 10/19 patients maintained clinical response after 6 months. Microbiota richness was higher in responders compared with the non-responders. Peptostreptococcus, Lactobacillus, and Veillonella were higher in non-responders, while Parabacteroides, Bacteroides, Faecalibacterium, and Akkermansia were higher in responders at all timepoints. Serial FMT infusions appear to be feasible, safe, and effective in UC patients, with a potential role in inducing and maintaining clinical response. Specific bacteria predict the response to FMT.

RevDate: 2023-10-30

Cláudia-Ferreira A, Barbosa DJ, Saegeman V, et al (2023)

The Future Is Now: Unraveling the Expanding Potential of Human (Necro)Microbiome in Forensic Investigations.

Microorganisms, 11(10):.

The relevance of postmortem microbiological examinations has been controversial for decades, but the boom in advanced sequencing techniques over the last decade is increasingly demonstrating their usefulness, namely for the estimation of the postmortem interval. This comprehensive review aims to present the current knowledge about the human postmortem microbiome (the necrobiome), highlighting the main factors influencing this complex process and discussing the principal applications in the field of forensic sciences. Several limitations still hindering the implementation of forensic microbiology, such as small-scale studies, the lack of a universal/harmonized workflow for DNA extraction and sequencing technology, variability in the human microbiome, and limited access to human cadavers, are discussed. Future research in the field should focus on identifying stable biomarkers within the dominant Bacillota and Pseudomonadota phyla, which are prevalent during postmortem periods and for which standardization, method consolidation, and establishment of a forensic microbial bank are crucial for consistency and comparability. Given the complexity of identifying unique postmortem microbial signatures for robust databases, a promising future approach may involve deepening our understanding of specific bacterial species/strains that can serve as reliable postmortem interval indicators during the process of body decomposition. Microorganisms might have the potential to complement routine forensic tests in judicial processes, requiring robust investigations and machine-learning models to bridge knowledge gaps and adhere to Locard's principle of trace evidence.

RevDate: 2023-10-30
CmpDate: 2023-10-30

Mukherjee P, Paul S, Dutta T, et al (2023)

Nasal MRSA carriage is a risk factor for development of antibiotic resistance in diabetic foot ulcers and is significantly higher than diabetic and non-diabetic individuals without foot ulcer.

BMC infectious diseases, 23(1):729.

BACKGROUND: Diabetic foot ulcer (DFU) is a major complication of diabetes often impacted by polymicrobial infection in the wound site. Diabetic patients are immunocompromised in nature and hence vulnerable to infection once the skin barrier is breached. Microbiological culture-based methods show that Staphylococcus aureus (SA) is the most frequently isolated bacteria from the DFU wounds. SA and its most clinically important antibiotic resistant variant methicillin-resistant S. aureus (MRSA) are commonly found in the nasal vestibule and colonization of SA as well as MRSA in any wound site can aggravate the condition. We hypothesize that the presence of nasal MRSA carriage can serve as a potential risk factor contributing to the emergence of antibiotic resistance in diabetic foot ulcer wounds.

METHODS: In the present study, we have compared the carriage of SA and MRSA in nasal cavity and foot skin among DFU patients (D+F+, n = 50), diabetic patients without any ulcer (D+F-, n = 50), and healthy controls (D-F-, n = 40) by using bacterial culture and PCR based methods. The D+F+, D+F- and D-F-individuals were further categorized based on the presence or absence of MRSA and clinical parameters were compared between MRSA+ ve and MRSA-ve individuals in each of the three groups mentioned above.

RESULTS: Our results show that, (a) nasal MRSA carriage is significantly higher (p < 0.05) in D+F+ group than the D+F- and D-F- and significantly associated with wound MRSA carriage in D+ F+ individuals (O.R. = 4.09; 95% C.I. = 1.12-15.05) and (b) the HbA1C level is significantly higher (p < 0.02) in wound MRSA positive, compared to MRSA negative D+F+ patients. Interestingly more than half of the MRSA (64%) isolated from DFU wound were identified to be multidrug resistant.

CONCLUSION: These findings strongly suggest that nasal MRSA carriage can act as a risk factor for development of antibiotic resistance in diabetic foot ulcers and it is therefore important to screen nasal and wound sites of these patients regularly. We have also developed a rapid multiplex PCR assay to detect MRSA from clinical isolates or microbial DNA isolated from clinical samples in the hospital settings.

RevDate: 2023-10-26

Steinbach E, Masi D, Ribeiro A, et al (2023)

Upper small intestine microbiome in obesity and related metabolic disorders: A new field of investigation.

Metabolism: clinical and experimental pii:S0026-0495(23)00316-5 [Epub ahead of print].

The study of the gut microbiome holds great promise for understanding and treating metabolic diseases, as its functions and derived metabolites can influence the metabolic status of the host. While research on the fecal microbiome has provided valuable insights, it tells us only part of the story. This limitation arises from the substantial variations in microorganism distribution throughout the gastrointestinal tract due to changes in physicochemical conditions. Thus, relying solely on the fecal microbiome may not be sufficient to draw comprehensive conclusions about metabolic diseases. The proximal part of the small intestine, particularly the jejunum, indeed, serves as the crucial site for digestion and absorption of nutrients, suggesting a potential role of its microbiome in metabolic regulation. Unfortunately, it remains relatively underexplored due to limited accessibility. This review presents current evidence regarding the relationships between the microbiome in the upper small intestine and various phenotypes, focusing on obesity and type 2 diabetes, in both humans and rodents. Research on humans is still limited with variability in the population and methods used. Accordingly, to better understand the role of the whole gut microbiome in metabolic diseases, studies exploring the human microbiome in different niches are needed.

RevDate: 2023-11-10

Blanco-Míguez A, Gálvez EJC, Pasolli E, et al (2023)

Extension of the Segatella copri complex to 13 species with distinct large extrachromosomal elements and associations with host conditions.

Cell host & microbe, 31(11):1804-1819.e9.

The Segatella copri (formerly Prevotella copri) complex (ScC) comprises taxa that are key members of the human gut microbiome. It was previously described to contain four distinct phylogenetic clades. Combining targeted isolation with large-scale metagenomic analysis, we defined 13 distinct Segatella copri-related species, expanding the ScC complex beyond four clades. Complete genome reconstruction of thirteen strains from seven species unveiled the presence of genetically diverse large circular extrachromosomal elements. These elements are consistently present in most ScC species, contributing to intra- and inter-species diversities. The nine species-level clades present in humans display striking differences in prevalence and intra-species genetic makeup across human populations. Based on a meta-analysis, we found reproducible associations between members of ScC and the male sex and positive correlations with lower visceral fat and favorable markers of cardiometabolic health. Our work uncovers genomic diversity within ScC, facilitating a better characterization of the human microbiome.

RevDate: 2023-10-26

Om H, Chand U, PK Kushawaha (2023)

Human anaerobic microbiome: a promising and innovative tool in cancer prevention and treatment by targeting pyruvate metabolism.

Cancer immunology, immunotherapy : CII [Epub ahead of print].

INTRODUCTION: Even in present-day times, cancer is one of the most fatal diseases. People are overwhelmed by pricey chemotherapy, immunotherapy, and other costly cancer therapies in poor and middle-income countries. Cancer cells grow under anaerobic and hypoxic conditions. Pyruvate is the final product of the anaerobic glycolysis pathway, and many cancer cells utilize pyruvate for their growth and development. The anaerobic microbiome produces many anti-cancer substances that can act as anti-tumor agents and are both feasible and of low cost. There are different mechanisms of action of the anaerobic microbiome, such as the production of short-chain fatty acids (SCFAs), and competition for the anaerobic environment includes the metabolic product pyruvate to form lactic acid for energy.

KEY FINDINGS: In this review, we have summarized the role of the metabolic approach of the anaerobic human microbiome in cancer prevention and treatment by interfering with cancer metabolite pyruvate. SCFAs possess decisive outcomes in condoning almost all the hallmarks of cancer and helping the spread of cancer to other body parts. Studies have demonstrated the impact and significance of using SCFA, which results from anaerobic bacteria, as an anti-cancer agent. Anaerobic bacteria-based cancer therapy has become a promising approach to treat cancer using obligate and facultative anaerobic bacteria because of their ability to penetrate and increase in an acidic hypoxic environment.

SIGNIFICANCE: This review attempts to provide the interconnection of cancer metabolism and anaerobic microbiome metabolism with a focus on pyruvate metabolism to understand and design unique anaerobic microbiota-based therapy for cancer patients.

RevDate: 2023-10-26

Väinämö S, Saqib S, Kalliala I, et al (2023)

Longitudinal analysis of vaginal microbiota during IVF fresh embryo transfer and in early pregnancy.

Microbiology spectrum [Epub ahead of print].

Non-Lactobacillus-dominated vaginal microbiota has been associated with poor gynecologic health and complications during pregnancy. Lactobacilli and especially Lactobacillus crispatus associate with good reproductive health and dominate the microbiota during healthy pregnancy. We examined whether the composition of vaginal microbiota at the time of fresh embryo transfer (ET) has an impact on the success of in vitro fertilization (IVF) and whether vaginal microbiota changes from IVF-ET to early pregnancy within individuals. Vaginal swab samples were collected from subfertile women at the time of IVF-ET (n = 76) and at the eighth gestational week (n = 21) from those who achieved clinical pregnancy. The microbiota composition was analyzed using 16S rRNA gene amplicon sequencing. L. crispatus was more abundant among the 30 women who achieved clinical pregnancy (46.9% vs. 19.1%, q = 0.039) and the 26 women who had live birth (43.3% vs. 23.1%, q = 0.32) compared to those who did not. Lactobacilli, mainly L. crispatus (76.2%), dominated all early pregnancy samples. Microbiota remained the same, i.e., Lactobacillus-dominated type in 52% (11/21), shifted from one Lactobacillus-dominated type to another in 24% (5/21), or shifted from mixed community to Lactobacillus-dominated type in 24% (5/21) women, but never from Lactobacillus dominance to non-lactobacilli dominance. Our results emphasize the role of L. crispatus in the success of IVF-ET and in early pregnancy. During pregnancy, the microbiota shifted toward L. crispatus dominance even if it was undetectable before pregnancy, indicating that most women hold a reservoir of this beneficial Lactobacillus in their reproductive tract.IMPORTANCEInfertility is a global public health issue which leads many couples to seek fertility treatments, of which in vitro fertilization (IVF) is considered to be the most effective. Still, only about one-third of the women achieve live birth after the first IVF embryo transfer (IVF-ET). Factors affecting embryo implantation are poorly known, but the female reproductive tract microbiota may play a key role. Our study confirms the beneficial role of vaginal lactobacilli, especially Lactobacillus crispatus, in the probability of achieving clinical pregnancy and live birth following IVF-ET. Our findings regarding the intra-individual shift of vaginal microbiota between non-pregnancy and pregnancy states are novel and provide new information about the dynamics of microbiota in the early steps of human reproduction. These findings may help clinicians in their attempts to optimize the conditions for ET by microbiota screening or modulation and timing the ET when the microbiota is the most favorable.

RevDate: 2023-10-31

Sampaio S, Araujo R, Merino-Riba A, et al (2023)

Blood, Gut, and Oral Microbiome in Kidney Transplant Recipients.

Indian journal of nephrology, 33(5):366-370.

BACKGROUND AND OBJECTIVE: Recent reports describe the existence of a blood microbiome profile not associated with an infection state. Given the high impact that the dysbiotic human microbiome appears to have in chronic kidney disease and, in particular, in the outcome of kidney transplant recipients (KTRs), we aimed to explore the variations and correlations of the gut, oral, and blood microbiome of recipients, 3 months after kidney transplantation.

MATERIALS AND METHODS: We conducted a cross-sectional study where the microbiome of stool, saliva, and blood collected from recipients 3 months after kidney transplantation (N = 6) was analyzed by polymerase chain reaction (PCR) amplification and sequencing of the V3-V4 hypervariable regions of the 16S rRNA gene using MiSeq Illumina[®] technology.

RESULTS: Blood of KTRs harbors a distinct low-abundance microbiome dominated by Proteobacteria and Firmicutes. Gut and oral microbiome of KTRs also present distinct profiles. The existence of a proportion of shared operational taxonomic units among the different body sites is reported, mainly classified as Proteobacteria and Firmicutes.

CONCLUSIONS: This study provides evidence of existence a blood microbiome in KTRs, different from the gut and the oral microbiome profiles, with a small number of operational taxonomic units representing a shared microbiome. The clinical relevance of this observation should be further explored in these patients.

RevDate: 2023-10-24

Li J, Yang Z, Yuan W, et al (2023)

Heme metabolism mediates the effects of smoking on gut microbiome.

Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco pii:7329327 [Epub ahead of print].

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 among smoking, host gene expression, and the gut microbiome is limited.

METHODS: We first explored transcriptome and metagenome profile differences between smokers and non-smokers. To evaluate the relationship between host gene expression and gut microbiome, we then applied bi-directional mediation analysis to infer causal relationships between smoking, gene expression, and gut microbes.

RESULTS: Metagenome and transcriptome analyses revealed 71 differential species and 324 differential expressed genes between smokers and non-smokers. 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.

CONCLUSIONS: By investigating the bi-directional 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.

IMPLICATIONS: By comparing the metagenome and transcriptome sequencing profiles between 34 smokers and 33 age- and gender-matched non-smokers, 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.

RevDate: 2023-10-30

Vänni P, Tejesvi MV, Paalanne N, et al (2023)

Machine-learning analysis of cross-study samples according to the gut microbiome in 12 infant cohorts.

mSystems [Epub ahead of print].

Combining and comparing microbiome data from distinct infant cohorts has been challenging because such data are inherently multidimensional and complex. Here, we used an ensemble of machine-learning (ML) models and studied 16S rRNA amplicon sequencing data from 4,099 gut microbiome samples representing 12 prospectively collected infant cohorts. We chose the childbirth delivery mode as a starting point for such analysis because it has previously been associated with alterations in the gut microbiome in infants. In cross-study ensemble models, Bacteroides was the most important feature in all machine-learning models. The predictive capacity by taxonomy varied with age. At the age of 1-2 months, gut microbiome data were able to predict delivery mode with an area under the curve of 0.72 to 0.83. In contrast, ML models trained on taxa were not able to differentiate between the modes of delivery, in any of the cohorts, when the infants were between 3 and 12 months of age. Moreover, no ML model, alternately trained on the functional pathways of the infant gut microbiome, could consistently predict mode of delivery at any infant age. This study shows that infant gut microbiome data sets can be effectively combined with the application of ML analysis across different study populations.IMPORTANCEThere are challenges in merging microbiome data from diverse research groups due to the intricate and multifaceted nature of such data. To address this, we utilized a combination of machine-learning (ML) models to analyze 16S sequencing data from a substantial set of gut microbiome samples, sourced from 12 distinct infant cohorts that were gathered prospectively. Our initial focus was on the mode of delivery due to its prior association with changes in infant gut microbiomes. Through ML analysis, we demonstrated the effective merging and comparison of various gut microbiome data sets, facilitating the identification of robust microbiome biomarkers applicable across varied study populations.

RevDate: 2023-10-30

Abdill RJ, Graham SP, Rubinetti V, et al (2023)

Integration of 168,000 samples reveals global patterns of the human gut microbiome.

bioRxiv : the preprint server for biology.

Understanding the factors that shape variation in the human microbiome is a major goal of research in biology. While other genomics fields have used large, pre-compiled compendia to extract systematic insights requiring otherwise impractical sample sizes, there has been no comparable resource for the 16S rRNA sequencing data commonly used to quantify microbiome composition. To help close this gap, we have assembled a set of 168,484 publicly available human gut microbiome samples, processed with a single pipeline and combined into the largest unified microbiome dataset to date. We use this resource, which is freely available at, to shed light on global variation in the human gut microbiome. We find that Firmicutes, particularly Bacilli and Clostridia, are almost universally present in the human gut. At the same time, the relative abundance of the 65 most common microbial genera differ between at least two world regions. We also show that gut microbiomes in undersampled world regions, such as Central and Southern Asia, differ significantly from the more thoroughly characterized microbiomes of Europe and Northern America. Moreover, humans in these overlooked regions likely harbor hundreds of taxa that have not yet been discovered due to this undersampling, highlighting the need for diversity in microbiome studies. We anticipate that this new compendium can serve the community and enable advanced applied and methodological research.

RevDate: 2023-10-30

Anderson DM, Logan MG, Patty SS, et al (2023)

Microbiome imaging goes à la carte: Incorporating click chemistry into the fluorescence-activating and absorption-shifting tag (FAST) imaging platform.

bioRxiv : the preprint server for biology.

The human microbiome is predominantly composed of facultative and obligate anaerobic bacteria that live in hypoxic/anoxic polymicrobial biofilm communities. Given the oxidative sensitivity of large fractions of the human microbiota, green fluorescent protein (GFP) and related genetically-encoded fluorophores only offer limited utility for live cell imaging due the oxygen requirement for chromophore maturation. Consequently, new fluorescent imaging modalities are needed to study polymicrobial interactions and microbiome-host interactions within anaerobic environments. The fluorescence-activating and absorption shifting tag (FAST) is a rapidly developing genetically-encoded fluorescent imaging technology that exhibits tremendous potential to address this need. In the FAST system, fluorescence only occurs when the FAST protein is complexed with one of a suite of cognate small molecule fluorogens. To expand the utility of FAST imaging, we sought to develop a modular platform (Click-FAST) to democratize fluorogen engineering for personalized use cases. Using Click-FAST, investigators can quickly and affordably sample a vast chemical space of compounds, potentially imparting a broad range of desired functionalities to the parental fluorogen. In this work, we demonstrate the utility of the Click-FAST platform using a novel fluorogen, [PL]Blaze-alkyne, which incorporates the widely available small molecule ethylvanillin as the hydroxybenzylidine head group. Different azido reagents were clicked onto [PL]Blaze-alkyne and shown to impart useful characteristics to the fluorogen, such as selective bacterial labeling in mixed populations as well as fluorescent signal enhancement. Conjugation of an 80 Å PEG molecule to [PL]Blaze-alkyne illustrates the broad size range of functional fluorogen chimeras that can be employed. This PEGylated fluorogen also functions as an exquisitely selective membrane permeability marker capable of outperforming propidium iodide as a fluorescent marker of cell viability.

RevDate: 2023-10-23

Wang M, Liu G, Liu M, et al (2023)

ICEberg 3.0: functional categorization and analysis of the integrative and conjugative elements in bacteria.

Nucleic acids research pii:7327075 [Epub ahead of print].

ICEberg 3.0 ( is an upgraded database that provides comprehensive insights into bacterial integrative and conjugative elements (ICEs). In comparison to the previous version, three key enhancements were introduced: First, through text mining and manual curation, it now encompasses details of 2065 ICEs, 607 IMEs and 275 CIMEs, including 430 with experimental support. Secondly, ICEberg 3.0 systematically categorizes cargo gene functions of ICEs into six groups based on literature curation and predictive analysis, providing a profound understanding of ICEs'diverse biological traits. The cargo gene prediction pipeline is integrated into the online tool ICEfinder 2.0. Finally, ICEberg 3.0 aids the analysis and exploration of ICEs from the human microbiome. Extracted and manually curated from 2405 distinct human microbiome samples, the database comprises 1386 putative ICEs, offering insights into the complex dynamics of Bacteria-ICE-Cargo networks within the human microbiome. With the recent updates, ICEberg 3.0 enhances its capability to unravel the intricacies of ICE biology, particularly in the characterization and understanding of cargo gene functions and ICE interactions within the microbiome. This enhancement may facilitate the investigation of the dynamic landscape of ICE biology and its implications for microbial communities.

RevDate: 2023-10-30

Ibrahimi E, Lopes MB, Dhamo X, et al (2023)

Overview of data preprocessing for machine learning applications in human microbiome research.

Frontiers in microbiology, 14:1250909.

Although metagenomic sequencing is now the preferred technique to study microbiome-host interactions, analyzing and interpreting microbiome sequencing data presents challenges primarily attributed to the statistical specificities of the data (e.g., sparse, over-dispersed, compositional, inter-variable dependency). This mini review explores preprocessing and transformation methods applied in recent human microbiome studies to address microbiome data analysis challenges. Our results indicate a limited adoption of transformation methods targeting the statistical characteristics of microbiome sequencing data. Instead, there is a prevalent usage of relative and normalization-based transformations that do not specifically account for the specific attributes of microbiome data. The information on preprocessing and transformations applied to the data before analysis was incomplete or missing in many publications, leading to reproducibility concerns, comparability issues, and questionable results. We hope this mini review will provide researchers and newcomers to the field of human microbiome research with an up-to-date point of reference for various data transformation tools and assist them in choosing the most suitable transformation method based on their research questions, objectives, and data characteristics.

RevDate: 2023-10-31
CmpDate: 2023-10-31

Tan A, Murugapiran S, Mikalauskas A, et al (2023)

Rational probe design for efficient rRNA depletion and improved metatranscriptomic analysis of human microbiomes.

BMC microbiology, 23(1):299.

The microbiota that colonize the human gut and other tissues are dynamic, varying both in composition and functional state between individuals and over time. Gene expression measurements can provide insights into microbiome composition and function. However, efficient and unbiased removal of microbial ribosomal RNA (rRNA) presents a barrier to acquiring metatranscriptomic data. Here we describe a probe set that achieves efficient enzymatic rRNA removal of complex human-associated microbial communities. We demonstrate that the custom probe set can be further refined through an iterative design process to efficiently deplete rRNA from a range of human microbiome samples. Using synthetic nucleic acid spike-ins, we show that the rRNA depletion process does not introduce substantial quantitative error in gene expression profiles. Successful rRNA depletion allows for efficient characterization of taxonomic and functional profiles, including during the development of the human gut microbiome. The pan-human microbiome enzymatic rRNA depletion probes described here provide a powerful tool for studying the transcriptional dynamics and function of the human microbiome.

RevDate: 2023-10-20

Budzinski L, Goetze VV, HD Chang (2023)

Single-cell phenotyping of bacteria combined with deep sequencing for improved contextualization of microbiome analyses.

European journal of immunology [Epub ahead of print].

Great effort was made to characterize the bacterial communities inhabiting the human body as a factor in disease, resulting in the realization that a wide spectrum of diseases is associated with an altered composition of the microbiome. However, the identification of disease-relevant bacteria has been hindered by the high cross-sectional diversity of individual microbiomes, and in most cases, it remains unclear whether the observed alterations are cause or consequence of disease. Hence, innovative analysis approaches are required that enable inquiries of the microbiome beyond mere taxonomic cataloguing. This review highlights the utility of microbiota flow cytometry, a single-cell analysis platform to directly interrogate cellular interactions, cell conditions and crosstalk with the host's immune system within the microbiome to take into consideration the role of microbes as critical interaction partners of the host and the spectrum of microbiome alterations, beyond compositional changes. In conjunction with advanced sequencing approaches it could reveal the genetic potential of target bacteria and advance our understanding of taxonomic diversity and gene usage in the context of the microenvironment. Single-cell bacterial phenotyping has the potential to change our perspective on the human microbiome and empower microbiome research for the development of microbiome-based therapy approaches and personalised medicine. This article is protected by copyright. All rights reserved.

RevDate: 2023-11-10
CmpDate: 2023-10-23

Farias Amorim C, Lovins VM, Singh TP, et al (2023)

Multiomic profiling of cutaneous leishmaniasis infections reveals microbiota-driven mechanisms underlying disease severity.

Science translational medicine, 15(718):eadh1469.

Leishmania braziliensis is a parasitic infection that can result in inflammation and skin injury with highly variable and unpredictable clinical outcomes. Here, we investigated the potential impact of microbiota on infection-induced inflammatory responses and disease resolution by conducting an integrated analysis of the skin microbiome and host transcriptome on a cohort of 62 patients infected with L. braziliensis. We found that overall bacterial burden and microbiome configurations dominated with Staphylococcus spp. were associated with delayed healing and enhanced inflammatory responses, especially by IL-1 family members. Quantification of host and bacterial transcripts on human lesions revealed that high lesional S. aureus transcript abundance was associated with delayed healing and increased expression of IL-1β. This cytokine was critical for modulating disease outcomes in L. braziliensis-infected mice colonized with S. aureus, given that its neutralization reduced pathology and inflammation. These results highlight how the human microbiome can shape disease outcomes in cutaneous leishmaniasis and suggest pathways toward host-directed therapies to mitigate the inflammatory consequences.

RevDate: 2023-10-18

Li S, Su B, Wu H, et al (2023)

Integrated analysis of gut and oral microbiome in men who have sex with men with HIV Infection.

Microbiology spectrum [Epub ahead of print].

Human immunodeficiency virus (HIV) infection leads to severe deficiency in host immunity by depletion of CD4[+] T-cells, resulting in an imbalance between the human microbiome and host immune response. Alterations in both gut and oral microbiomes have been observed in people living with HIV (PLWH). However, the impact of an altered gut and oral microbiome on HIV disease progression and the relationship between them in PLWH have not been explored. In this longitudinal study, we enrolled acute HIV-infected men who have sex with men (MSM) (n = 15), chronic HIV-infected MSM (n = 15), and HIV-uninfected MSM controls (n = 15). We collected anal and throat swab samples at recruitment (W0) from all participants and at 12 wk after antiretroviral therapy (ART) (W12) from the patients and performed 16S rRNA gene sequencing of genomic DNAs extracted from these swabs. In HIV-infected individuals with CD4 T-cell counts < 350 cells/µL, the increase in abundance of Streptococcus in the oral microbiome was inversely correlated with that of Streptococcus in the gut microbiome (r = -0.490, P = 0.039). In addition, the lower CD4[+] T-cell counts (<200 cells/µL) were associated with the higher abundance of Escherichia-Shigella and the lower abundance of Methylobacterium-Methylorubrum of the gut microbiome in HIV-infected individuals. We demonstrate the alteration of gut microbiome resulting from HIV infection and ART and the relationship between the gut and oral microbiome in PLWH and controls. These findings highlight the need for a better understanding of the interactions between the oral and gut microbiome and its potential role in HIV disease progression. IMPORTANCE Our longitudinal integrated study has shown the marked alterations in the gut and oral microbiome resulting from acute and chronic HIV infection and from antiretroviral therapy. Importantly, the relationship between oral and gut microbiomes in people living with acute and chronic HIV infection and "healthy" controls has also been explored. These findings might contribute to a better understanding of the interactions between the oral and gut microbiomes and its potential role in HIV disease progression.

RevDate: 2023-11-04
CmpDate: 2023-11-02

Refisch A, M Walter (2023)

[The importance of the human microbiome for mental health].

Der Nervenarzt, 94(11):1001-1009.

Many common diseases including psychiatric disorders show characteristic alterations in the microbiome. Preclinical studies have uncovered important mechanisms by which the microbiome interacts bidirectionally with neural functions. Dysregulation of the complex interplay between the microbiome, immune system, stress response, and energy homeostasis, particularly in the early stages of life, can predispose to the development of psychiatric symptoms later in life. Although few clinical studies are available to date, the broad influence of the microbiome on neural and mental functions as well as its high plasticity, have generated great interest in its therapeutic potential for common psychiatric disorders.

RevDate: 2023-10-17

Sun L, Wang Q, Wang H, et al (2023)

A cross-sectional cohort study on the skin microbiota in patients with different acne durations.

Experimental dermatology [Epub ahead of print].

Acne is a chronic disease that often persists for years. Skin microbial communities play an essential role in the development of acne. However, limited information is available about the dynamic patterns of skin microbiota in acne. This study aimed to characterize microbial community changes in skin pores and surfaces of acne patients with varying disease time. In this study, a total of 70 skin samples from 22 subjects were collected and sequenced using 16S rRNA amplicon sequencing. Although microbial compositions in skin pores were similar over time, significant differences in microbial structure were observed on the skin surface, with the dominance of Cutibacterium in the first 3 years and replacement by Staphylococcus in 4-6 years. Lactobacillus and Acinetobacter were more abundant in the normal group and continuingly decreased with disease time on the skin surface. Microbial networks further revealed substantial increases in microbial interactions in the 4-6 years group in both skin surfaces and pores. These results demonstrate that the skin microbiota alters with the disease duration and may provide a potential guide in redirecting skin microbiota towards healthy states.

RevDate: 2023-10-16

Shad NS, Shaikh NI, SA Cunningham (2023)

Migration Spurs Changes in the Human Microbiome: a Review.

Journal of racial and ethnic health disparities [Epub ahead of print].

International migration often results in major changes in living environments and lifestyles, and these changes may lead to the observed increases in obesity and diabetes among foreign-born people after resettling in higher-income countries. A possible mechanism linking changes in living environments to the onset of health conditions may be changes in the microbiome. Previous research has shown that unfavorable changes in the composition of the microbiome can increase disposition to diseases such as diabetes, obesity, kidney disease, and inflammatory bowel disease. We investigated the relationship between human migration and microbiome composition through a review using microbiome- and migration-related search terms in PubMed and Web of Science. We included articles examining the gut, oral, or oropharyngeal microbiome in people who migrated internationally. Nine articles met eligibility criteria. All but one examined migration from a non-Western to a Western country. Four of these found a difference in the microbiome of migrants compared with non-migrating residents of their country of birth, seven found differences in the microbiome of migrants compared with the native-born population in the country of resettlement, and five found microbiome differences associated with duration of stay in the country of resettlement. Microbiome composition varies with country of birth, age at migration, time since immigration, and country of resettlement. The results suggest that migration may lead to changes in the microbiome; thus, microbiome characteristics are a plausible pathway to examine changes in health after resettlement in a new country.

RevDate: 2023-10-16

Moitas B, Caldas IM, B Sampaio-Maia (2023)

Microbiology and postmortem interval: a systematic review.

Forensic science, medicine, and pathology [Epub ahead of print].

This systematic review aims to learn if and how it is possible to use the human microbiome to indicate the time elapsed after death. Articles were searched on the PubMed database using predefined data fields and keywords; reviews, systematic reviews, and meta-analyses were excluded. The final selection included 14 papers (out of 144). The results indicated that the microorganisms present in the cadaveric island succeed predictably over time, with markers between the stages of decomposition constituting a potential innovative tool for postmortem interval (PMI) estimation. The human microbiome has the potential to be used for PMI estimation and may present advantages as microbes are present in all seasons, in all habitats, including the most extreme ones, and because microbial communities respond predictably to environmental changes.

RevDate: 2023-10-20

Zhou R, Ng SK, Sung JJY, et al (2023)

Data pre-processing for analyzing microbiome data - A mini review.

Computational and structural biotechnology journal, 21:4804-4815.

The human microbiome is an emerging research frontier due to its profound impacts on health. High-throughput microbiome sequencing enables studying microbial communities but suffers from analytical challenges. In particular, the lack of dedicated preprocessing methods to improve data quality impedes effective minimization of biases prior to downstream analysis. This review aims to address this gap by providing a comprehensive overview of preprocessing techniques relevant to microbiome research. We outline a typical workflow for microbiome data analysis. Preprocessing methods discussed include quality filtering, batch effect correction, imputation of missing values, normalization, and data transformation. We highlight strengths and limitations of each technique to serve as a practical guide for researchers and identify areas needing further methodological development. Establishing robust, standardized preprocessing will be essential for drawing valid biological conclusions from microbiome studies.

RevDate: 2023-10-20

Jang H, Park S, H Koh (2023)

Comprehensive microbiome causal mediation analysis using MiMed on user-friendly web interfaces.

Biology methods & protocols, 8(1):bpad023.

It is a central goal of human microbiome studies to see the roles of the microbiome as a mediator that transmits environmental, behavioral, or medical exposures to health or disease outcomes. Yet, mediation analysis is not used as much as it should be. One reason is because of the lack of carefully planned routines, compilers, and automated computing systems for microbiome mediation analysis (MiMed) to perform a series of data processing, diversity calculation, data normalization, downstream data analysis, and visualizations. Many researchers in various disciplines (e.g. clinicians, public health practitioners, and biologists) are not also familiar with related statistical methods and programming languages on command-line interfaces. Thus, in this article, we introduce a web cloud computing platform, named as MiMed, that enables comprehensive MiMed on user-friendly web interfaces. The main features of MiMed are as follows. First, MiMed can survey the microbiome in various spheres (i) as a whole microbial ecosystem using different ecological measures (e.g. alpha- and beta-diversity indices) or (ii) as individual microbial taxa (e.g. phyla, classes, orders, families, genera, and species) using different data normalization methods. Second, MiMed enables covariate-adjusted analysis to control for potential confounding factors (e.g. age and gender), which is essential to enhance the causality of the results, especially for observational studies. Third, MiMed enables a breadth of statistical inferences in both mediation effect estimation and significance testing. Fourth, MiMed provides flexible and easy-to-use data processing and analytic modules and creates nice graphical representations. Finally, MiMed employs ChatGPT to search for what has been known about the microbial taxa that are found significantly as mediators using artificial intelligence technologies. For demonstration purposes, we applied MiMed to the study on the mediating roles of oral microbiome in subgingival niches between e-cigarette smoking and gingival inflammation. MiMed is freely available on our web server (

RevDate: 2023-10-15

Frey-Furtado L, Magalhães I, Sampaio-Maia B, et al (2023)

Oral microbiome characterization in oral mucositis patients-A systematic review.

Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology [Epub ahead of print].

BACKGROUND: Oral mucositis (OM) is a severe and common adverse effect of cancer treatment. The oral microbiome appears to play a role on the onset and severity of OM. Therefore, this systematic review aims to characterize the oral dysbiosis associated with OM.

METHODS: The PRISMA checklist was followed and PubMed, Web of Science, and Scopus were screened for clinical studies characterizing the oral microbiome alterations in patients with OM.

RESULTS: From a total of 2500 articles retrieved, we included nine articles in this systematic review. Certain types of bacteria, as Fusobacterium, were recognized as predictors of the onset of OM. In addition, it was reported that patients with severe OM presented a reduction in alpha-diversity, an increase in beta-diversity. The abundance of some taxa significantly changed with OM severity, with Bacillota phylum and genera Leptotrichia, Actinomyces, and Prevotella decreasing and Treponema increasing with disease progression. Additionally, during cancer treatment, changes in the oral microbiome have been observed in OM patients, with an increase in Candida and nosocomial pathogens, including Staphylococcus species.

CONCLUSION: Our review indicates that cancer treatment can significantly alter the oral microbiome, with more pronounced changes observed in patients with severe OM in all relevant oral phyla, but more pronounced in Bacillota phylum.

RevDate: 2023-10-20

Man MA, Ungur RA, Motoc NS, et al (2023)

Lung Microbiota in Idiopathic Pulmonary Fibrosis, Hypersensitivity Pneumonitis, and Unclassified Interstitial Lung Diseases: A Preliminary Pilot Study.

Diagnostics (Basel, Switzerland), 13(19):.

(1) Introduction: Although historically, the lung has been considered a sterile organ, recent studies through 16S rRNA gene sequencing have identified a substantial number of microorganisms. The human microbiome has been considered an "essential organ," carrying about 150 times more information (genes) than are found in the entire human genome. The purpose of the present study is to characterize and compare the microbiome in three different interstitial lung diseases: idiopathic pulmonary fibrosis (IPF), hypersensitivity pneumonitis, and nondifferential interstitial lung disease. (2) Material and methods: This was a prospective cohort study where the DNA of 28 patients with ILD was extracted from the lavage and then processed using the standard technique of 16S RNA gene sequencing. In a tertiary teaching hospital in the northern, western part of Romania, samples were collected through bronchoscopy and then processed. (3) Results: The same four species were found in all the patients but in different quantities and compositions: Firmicutes, Actinobacteria, Proteobacteria and Bacteroides. Streptococcus was the most prevalent genus, followed by Staphylococcus and Prevotella. Statistically significant differences in the OUT count for the ten most abundant taxa were found for the genus: Gemella, Actinobacteria, Prevotella, Neisseria, Haemophilus, and Bifidobacterium. The comparative analysis showed a richer microbiota in patients with IPF, as shown by the alpha diversity index. (4) Conclusions: In interstitial lung diseases, the microorganisms normally found in the lung are reduced to a restricted flora dominated by the Firmicutes family. These changes significantly disrupt the continuity of the observed bacterial pattern from the oropharynx to the bronchial tree and lung, possibly impacting the evolution and severity of interstitial lung diseases.

RevDate: 2023-11-01
CmpDate: 2023-11-01

Mascellino MT (2023)

Molecular Research in Human Microbiome.

International journal of molecular sciences, 24(19):.

Recent evidence has shown that the human microbiome is associated with a wide range of diseases, from non-neoplastic to tumourigenesis, including cancer, inflammation, intestinal damage, etc [...].

RevDate: 2023-11-01
CmpDate: 2023-11-01

Ma C, Yang C, Peng A, et al (2023)

Pan-cancer spatially resolved single-cell analysis reveals the crosstalk between cancer-associated fibroblasts and tumor microenvironment.

Molecular cancer, 22(1):170.

Cancer-associated fibroblasts (CAFs) are a heterogeneous cell population that plays a crucial role in remodeling the tumor microenvironment (TME). Here, through the integrated analysis of spatial and single-cell transcriptomics data across six common cancer types, we identified four distinct functional subgroups of CAFs and described their spatial distribution characteristics. Additionally, the analysis of single-cell RNA sequencing (scRNA-seq) data from three additional common cancer types and two newly generated scRNA-seq datasets of rare cancer types, namely epithelial-myoepithelial carcinoma (EMC) and mucoepidermoid carcinoma (MEC), expanded our understanding of CAF heterogeneity. Cell-cell interaction analysis conducted within the spatial context highlighted the pivotal roles of matrix CAFs (mCAFs) in tumor angiogenesis and inflammatory CAFs (iCAFs) in shaping the immunosuppressive microenvironment. In patients with breast cancer (BRCA) undergoing anti-PD-1 immunotherapy, iCAFs demonstrated heightened capacity in facilitating cancer cell proliferation, promoting epithelial-mesenchymal transition (EMT), and contributing to the establishment of an immunosuppressive microenvironment. Furthermore, a scoring system based on iCAFs showed a significant correlation with immune therapy response in melanoma patients. Lastly, we provided a web interface ( for the research community to investigate CAFs in the context of pan-cancer.

RevDate: 2023-10-16

Koh H (2023)

Subgroup Identification Using Virtual Twins for Human Microbiome Studies.

IEEE/ACM transactions on computational biology and bioinformatics, PP: [Epub ahead of print].

Even when the same treatment is employed, some patients are cured, while others are not. The patients that are cured may have beneficial microbes in their body that can boost treatment effects, but it is vice versa for the patients that are not cured. That is, treatment effects can vary depending on the patient's microbiome. If the effects of candidate treatments are well-predicted based on the patient's microbiome, we can select a treatment that is suited to the patient's microbiome or alter the patient's microbiome to improve treatment effects. Here, I introduce a streamlined analytic method, microbiome virtual twins (MiVT), to probe for the interplay between microbiome and treatment. MiVT employs a new prediction method, distance-based machine learning (dML), to improve prediction accuracy in microbiome studies and a new significance test, bootstrap-based test for regression tree (BoRT), to test if each subgroup's treatment effect is the same with the overall treatment effect. MiVT will serve as a useful guideline in microbiome-based personalized medicine to select the therapy that is most suited to the patient's microbiome or to tune the patient's microbiome to be suited to the treatment. MiVT can be implemented using an R package, MiVT, at

RevDate: 2023-10-11

Legakis I, Chrousos GP, S Chatzipanagiotou (2023)

Thyroid Diseases and Intestinal Microbiome.

Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme [Epub ahead of print].

The human microbiome plays an integral role in health. In particular, it is important for the development, differentiation and maturation of the immune system, 70% of which resides in the intestinal mucosa. Microbiome studies conducted to date have revealed an association between disturbances in the microbiota (dysbiosis) and various pathological disorders, including changes in host immune status. Autoimmune thyroid diseases are one of the most common organ-specific autoimmune disorders, with a worldwide prevalence higher than 5%. The predominant autoimmune thyroid diseases are Hashimoto's thyroiditis and Grave's disease. Several factors, such as genetic and environmental ones, have been studied. In accordance with recent studies, it is assumed that the gut microbiome might play a significant role in triggering autoimmune diseases of the thyroid gland. However, the exact etiology has not yet been elucidated. The present review aims to describe the work carried out so far regarding the role of gut microflora in the pathogenesis of autoimmune thyroid diseases and its involvement in the appearance of benign nodules and papillary thyroid cancer. It appears that future work is needed to elucidate more precisely the mechanism for gut microbiota involvement in the development of autoimmune thyroid diseases.

RevDate: 2023-10-11

Zhou T, Xiao L, Zuo Z, et al (2023)

MAMI: a comprehensive database of mother-infant microbiome and probiotic resources.

Nucleic acids research pii:7306670 [Epub ahead of print].

Extensive evidence has demonstrated that the human microbiome and probiotics confer great impacts on human health, particularly during critical developmental stages such as pregnancy and infancy when microbial communities undergo remarkable changes and maturation. However, a major challenge in understanding the microbial community structure and interactions between mothers and infants lies in the current lack of comprehensive microbiome databases specifically focused on maternal and infant health. To address this gap, we have developed an extensive database called MAMI (Microbiome Atlas of Mothers and Infants) that archives data on the maternal and neonatal microbiome, as well as abundant resources on edible probiotic strains. By leveraging this resource, we can gain profound insights into the dynamics of microbial communities, contributing to lifelong wellness for both mothers and infants through precise modulation of the developing microbiota. The functionalities incorporated into MAMI provide a unique perspective on the study of the mother-infant microbiome, which not only advance microbiome-based scientific research but also enhance clinical practice. MAMI is publicly available at

RevDate: 2023-11-07
CmpDate: 2023-11-01

Higashi DL, Zou Z, Qin H, et al (2024)

Employing Cloning-Independent Mutagenesis of Parvimonas micra for the Study of Cell Wall Biogenesis.

Methods in molecular biology (Clifton, N.J.), 2727:57-67.

The cell wall plays an important structural role for bacteria and is intimately tied to a variety of critical processes ranging from growth and differentiation to pathogenesis. Our understanding of cell wall biogenesis is primarily derived from a relatively small number of heavily studied model organisms. Consequently, these processes can only be inferred for the vast majority of prokaryotes, especially among groups of uncharacterized and/or genetically intractable organisms. Recently, we developed the first tractable genetic system for Parvimonas micra, which is a ubiquitous Gram-positive pathobiont of the human microbiome involved in numerous types of inflammatory infections as well as a variety of malignant tumors. P. micra is also the first, and currently only, member of the entire Tissierellia class of the Bacillota phylum in which targeted genetic manipulation has been demonstrated. Thus, it is now possible to study cell wall biogenesis mechanisms within a member of the Tissierellia, which may also reveal novel aspects of P. micra pathobiology. Herein, we describe a procedure for cloning-independent genetic manipulation of P. micra, including allelic replacement mutagenesis and genetic complementation. The described techniques are also similarly applicable for the study of other aspects of P. micra pathobiology and physiology.

RevDate: 2023-11-08
CmpDate: 2023-11-06

Lohse MB, Ziv N, AD Johnson (2023)

Variation in transcription regulator expression underlies differences in white-opaque switching between the SC5314 reference strain and the majority of Candida albicans clinical isolates.

Genetics, 225(3):.

Candida albicans, a normal member of the human microbiome and an opportunistic fungal pathogen, undergoes several morphological transitions. One of these transitions is white-opaque switching, where C. albicans alternates between 2 stable cell types with distinct cellular and colony morphologies, metabolic preferences, mating abilities, and interactions with the innate immune system. White-to-opaque switching is regulated by mating type; it is repressed by the a1/α2 heterodimer in a/α cells, but this repression is lifted in a/a and α/α mating type cells (each of which are missing half of the repressor). The widely used C. albicans reference strain, SC5314, is unusual in that white-opaque switching is completely blocked when the cells are a/α; in contrast, most other C. albicans a/α strains can undergo white-opaque switching at an observable level. In this paper, we uncover the reason for this difference. We show that, in addition to repression by the a1/α2 heterodimer, SC5314 contains a second block to white-opaque switching: 4 transcription regulators of filamentous growth are upregulated in this strain and collectively suppress white-opaque switching. This second block is missing in the majority of clinical strains, and, although they still contain the a1/α2 heterodimer repressor, they exhibit a/α white-opaque switching at an observable level. When both blocks are absent, white-opaque switching occurs at very high levels. This work shows that white-opaque switching remains intact across a broad group of clinical strains, but the precise way it is regulated and therefore the frequency at which it occurs varies from strain to strain.

RevDate: 2023-11-01

D'Elia D, Truu J, Lahti L, et al (2023)

Advancing microbiome research with machine learning: key findings from the ML4Microbiome COST action.

Frontiers in microbiology, 14:1257002.

The rapid development of machine learning (ML) techniques has opened up the data-dense field of microbiome research for novel therapeutic, diagnostic, and prognostic applications targeting a wide range of disorders, which could substantially improve healthcare practices in the era of precision medicine. However, several challenges must be addressed to exploit the benefits of ML in this field fully. In particular, there is a need to establish "gold standard" protocols for conducting ML analysis experiments and improve interactions between microbiome researchers and ML experts. The Machine Learning Techniques in Human Microbiome Studies (ML4Microbiome) COST Action CA18131 is a European network established in 2019 to promote collaboration between discovery-oriented microbiome researchers and data-driven ML experts to optimize and standardize ML approaches for microbiome analysis. This perspective paper presents the key achievements of ML4Microbiome, which include identifying predictive and discriminatory 'omics' features, improving repeatability and comparability, developing automation procedures, and defining priority areas for the novel development of ML methods targeting the microbiome. The insights gained from ML4Microbiome will help to maximize the potential of ML in microbiome research and pave the way for new and improved healthcare practices.

RevDate: 2023-10-15

McGuinness AJ, Stinson LF, Snelson M, et al (2023)

From hype to hope: Considerations in conducting robust microbiome science.

Brain, behavior, and immunity, 115:120-130 pii:S0889-1591(23)00285-4 [Epub ahead of print].

Microbiome science has been one of the most exciting and rapidly evolving research fields in the past two decades. Breakthroughs in technologies including DNA sequencing have meant that the trillions of microbes (particularly bacteria) inhabiting human biological niches (particularly the gut) can be profiled and analysed in exquisite detail. This microbiome profiling has profound impacts across many fields of research, especially biomedical science, with implications for how we understand and ultimately treat a wide range of human disorders. However, like many great scientific frontiers in human history, the pioneering nature of microbiome research comes with a multitude of challenges and potential pitfalls. These include the reproducibility and robustness of microbiome science, especially in its applications to human health outcomes. In this article, we address the enormous promise of microbiome science and its many challenges, proposing constructive solutions to enhance the reproducibility and robustness of research in this nascent field. The optimisation of microbiome science spans research design, implementation and analysis, and we discuss specific aspects such as the importance of ecological principals and functionality, challenges with microbiome-modulating therapies and the consideration of confounding, alternative options for microbiome sequencing, and the potential of machine learning and computational science to advance the field. The power of microbiome science promises to revolutionise our understanding of many diseases and provide new approaches to prevention, early diagnosis, and treatment.

RevDate: 2023-10-06

Hisatomi A, Tourlousse DM, Hamajima M, et al (2023)

Complete genome sequences of Ruminococcus torques strains JCM 36208 and JCM 36209, isolated from the feces of a healthy Japanese male.

Microbiology resource announcements [Epub ahead of print].

Here, we report the complete genome sequences of two Ruminococcus torques strains (JCM 36208 and JCM 36209) that were newly isolated from the feces of a healthy Japanese male. Both genomes consist of a single circular chromosome with a length of ~2.8 Mbp and a G+C content of 41.8%.

RevDate: 2023-11-07
CmpDate: 2023-11-02

Ückert AK, Rütschlin S, Gutbier S, et al (2023)

Identification of the bacterial metabolite aerugine as potential trigger of human dopaminergic neurodegeneration.

Environment international, 180:108229.

The causes of nigrostriatal cell death in idiopathic Parkinson's disease are unknown, but exposure to toxic chemicals may play some role. We followed up here on suggestions that bacterial secondary metabolites might be selectively cytotoxic to dopaminergic neurons. Extracts from Streptomyces venezuelae were found to kill human dopaminergic neurons (LUHMES cells). Utilizing this model system as a bioassay, we identified a bacterial metabolite known as aerugine (C10H11NO2S; 2-[4-(hydroxymethyl)-4,5-dihydro-1,3-thiazol-2-yl]phenol) and confirmed this finding by chemical re-synthesis. This 2-hydroxyphenyl-thiazoline compound was previously shown to be a product of a wide-spread biosynthetic cluster also found in the human microbiome and in several pathogens. Aerugine triggered half-maximal dopaminergic neurotoxicity at 3-4 µM. It was less toxic for other neurons (10-20 µM), and non-toxic (at <100 µM) for common human cell lines. Neurotoxicity was completely prevented by several iron chelators, by distinct anti-oxidants and by a caspase inhibitor. In the Caenorhabditis elegans model organism, general survival was not affected by aerugine concentrations up to 100 µM. When transgenic worms, expressing green fluorescent protein only in their dopamine neurons, were exposed to aerugine, specific neurodegeneration was observed. The toxicant also exerted functional dopaminergic toxicity in nematodes as determined by the "basal slowing response" assay. Thus, our research has unveiled a bacterial metabolite with a remarkably selective toxicity toward human dopaminergic neurons in vitro and for the dopaminergic nervous system of Caenorhabditis elegans in vivo. These findings suggest that microbe-derived environmental chemicals should be further investigated for their role in the pathogenesis of Parkinson's disease.

RevDate: 2023-10-29
CmpDate: 2023-10-23

Pompei S, Bella E, Weitz JS, et al (2023)

Metacommunity structure preserves genome diversity in the presence of gene-specific selective sweeps under moderate rates of horizontal gene transfer.

PLoS computational biology, 19(10):e1011532.

The horizontal transfer of genes is fundamental for the eco-evolutionary dynamics of microbial communities, such as oceanic plankton, soil, and the human microbiome. In the case of an acquired beneficial gene, classic population genetics would predict a genome-wide selective sweep, whereby the genome spreads clonally within the community and together with the beneficial gene, removing genome diversity. Instead, several sources of metagenomic data show the existence of "gene-specific sweeps", whereby a beneficial gene spreads across a bacterial community, maintaining genome diversity. Several hypotheses have been proposed to explain this process, including the decreasing gene flow between ecologically distant populations, frequency-dependent selection from linked deleterious allelles, and very high rates of horizontal gene transfer. Here, we propose an additional possible scenario grounded in eco-evolutionary principles. Specifically, we show by a mathematical model and simulations that a metacommunity where species can occupy multiple patches, acting together with a realistic (moderate) HGT rate, helps maintain genome diversity. Assuming a scenario of patches dominated by single species, our model predicts that diversity only decreases moderately upon the arrival of a new beneficial gene, and that losses in diversity can be quickly restored. We explore the generic behaviour of diversity as a function of three key parameters, frequency of insertion of new beneficial genes, migration rates and horizontal transfer rates.Our results provides a testable explanation for how diversity can be maintained by gene-specific sweeps even in the absence of high horizontal gene transfer rates.

RevDate: 2023-10-06
CmpDate: 2023-10-05

Shittu AR, Iwaloye OF, Ojewole AE, et al (2023)

The effects of per- and polyfluoroalkyl substances on environmental and human microorganisms and their potential for bioremediation.

Arhiv za higijenu rada i toksikologiju, 74(3):167-178.

Utilised in a variety of consumer products, per- and polyfluoroalkyl substances (PFAS) are major environmental contaminants that accumulate in living organisms due to their highly hydrophobic, lipophobic, heat-resistant, and non-biodegradable properties. This review summarizes their effects on microbial populations in soils, aquatic and biogeochemical systems, and the human microbiome. Specific microbes are insensitive to and even thrive with PFAS contamination, such as Escherichia coli and the Proteobacteria in soil and aquatic environments, while some bacterial species, such as Actinobacteria and Chloroflexi, are sensitive and drop in population. Some bacterial species, in turn, have shown success in PFAS bioremediation, such as Acidimicrobium sp. and Pseudomonas parafulva.

RevDate: 2023-10-19

Wakade RS, DJ Krysan (2023)

Comparative dynamics of gene expression during in vitro and in vivo Candida albicans filamentation.

bioRxiv : the preprint server for biology.

Candida albicans is one of them most common causes of fungal disease in humans and is a commensal member of the human microbiome. The ability of C. albicans to cause disease is tightly correlated with its ability to undergo a morphological transition from budding yeast to a filamentous form (hyphae and pseudohyphae). This morphological transition is accompanied by the induction of a set of well characterized hyphae-associated genes and transcriptional regulators. To date, the vast majority of data regarding this process has been based on in vitro studies of filamentation using a range of inducing conditions. Recently, we developed an in vivo imaging approach that allows the direct characterization of morphological transition during mammalian infection. Here, we couple this imaging assay with in vivo expression profiling to characterize the time course of in vivo filamentation and the accompanying changes in gene expression. We also compare in vivo observations to in vitro filamentation using a medium (RPMI 1640 tissue culture medium with 10% bovine calf serum) widely used to mimic host conditions. From these data, we make the following conclusions regarding in vivo and in vitro filamentation. First, the transcriptional programs regulating filamentation are rapidly induced in vitro and in vivo. Second, the tempo of filamentation in vivo is prolonged relative to in vitro filamentation and the period of high expression of genes associated with that process is also prolonged. Third, hyphae are adapting to changing infection environments after filamentation has reached steady-state.

RevDate: 2023-10-04

Pietilä JP, Häkkinen TA, Pakarinen L, et al (2023)

Treatment of Dientamoeba fragilis: A retrospective Finnish analysis of faecal clearance and clinical cure comparing four antiprotozoal drugs.

New microbes and new infections, 54:101179.

BACKGROUND: Dientamoeba fragilis (DF), the most common intestinal protozoal pathogen in affluent countries, causes asymptomatic or symptomatic infections with severity ranging from mild to disabling. Currently, many studies of treatment options only have small sample sizes and report results that are partly contradictory.

METHODS: Investigating data retrieved from Helsinki University Hospital and Helsinki City patient records, we searched for the most effective antiprotozoal in treating DF infections. To study microbiological clearance of DF, we collected laboratory results of control samples from patients given one of four commonly used antiprotozoals: doxycycline, metronidazole, paromomycin, or secnidazole. For patients symptomatic prior to antiprotozoal treatment, we also retrieved data on clinical outcomes. Furthermore, we explored factors associated with faecal clearance and clinical cure.

RESULTS: A total of 369 patients (median age 38) and 492 treatment episodes were included. Paromomycin (n ​= ​297) proved effective (clearance rate 83%), showing strong association with faecal clearance (aOR 18.08 [7.24-45.16], p ​< ​0.001). For metronidazole the rate was 42% (n ​= ​84), for secnidazole 37% (n ​= ​79), and doxycycline 22% (n ​= ​32). In pairwise comparisons, paromomycin outdid the three other regimens (p ​< ​0.001, χ[2] test). Faecal clearance was associated with clinical cure (aOR 5.85 [3.02-11.32], p ​< ​0.001).

CONCLUSIONS: Faecal clearance, strongly associated with clinical cure, is most effectively achieved with a course of paromomycin, followed by metronidazole, secnidazole and doxycycline. Our findings will be useful in devising treatment guidelines for adults with symptomatic D. fragilis infection.

RevDate: 2023-11-06
CmpDate: 2023-10-31

Zhang J, Deng J, Li J, et al (2023)

Changes of gut microbiota under different nutritional methods in elderly patients with severe COVID-19 and their relationship with prognosis.

Frontiers in immunology, 14:1260112.

BACKGROUND: The clinical progression of individuals afflicted with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection exhibits significant heterogeneity, particularly affecting the elderly population to a greater extent. Consequently, the association between nutrition and microbiota has garnered considerable interest. Hence, the objective of this study was to gather clinical data pertaining to the influence of diverse nutritional support interventions on the prognosis of geriatric patients with COVID-19, while additionally examining the fecal microbiota of these individuals to assess the repercussions of microecological alterations on their prognostic outcomes.

RESULTS: A total of 71 elderly patients diagnosed with severe COVID-19 were included in this study. These patients were subsequently divided into two groups, namely the enteral nutrition (EN) group and the parenteral nutrition (PN) group, based on the type of nutritional support therapy they received after admission. The occurrence of complications was observed in 10.4% of patients in the EN group, whereas it was significantly higher at 69.6% in the PN group (P<0.001). Furthermore, the 60-day mortality rate was 2.1% (1/48) in the EN group, while it was notably higher at 30.4% (7/23) in the PN group (P=0.001). To identify the independent predictors of 60-day mortality, stepwise logistic regression analysis was employed. Among different bacterial groups, Enterococcus_faecium (18.19%) and Pseudomonas_aeruginosa (1.91%) had higher average relative abundance in the PN group (P<0.05). However, the relative abundance of Ruminococcus was higher in the EN group. Further Spearman correlation analysis showed that Enterococcus_faecium was positively correlated with poor clinical prognosis, while Ruminococcus was negatively correlated with poor clinical prognosis.

CONCLUSIONS: This study shows that the changes in the composition of intestinal flora in elderly COVID-19 patients receiving different nutritional support strategies may be related to different clinical outcomes. The abundance of Enterococcus_faecium in elderly COVID-19 patients receiving PN is significantly increased and is closely related to poor clinical outcomes. It highlights the potential of microbiome-centric interventions to mitigate and manage COVID-19 in older adults with different nutritional support options.

RevDate: 2023-10-21

Liu S, Zhang S, Guo M, et al (2023)

Acoustic stimulation during sleep improves cognition and ameliorates Alzheimer's disease pathology in APP/PS1 mice.

Experimental gerontology, 182:112299.

Nonpharmacological therapies for Alzheimer's disease (AD) have become a popular research topic, and acoustic stimulation during sleep is one such promising strategy for the clinical treatment of AD. Some animal experiments have illustrated that acoustic stimulation at a specific frequency can ameliorate AD-related pathology or improve cognition in mice, but these studies did not explore the effective time window of auditory stimulation. Here, we explored the effects of acoustic stimulation during wakefulness and acoustic stimulation during sleep on cognition and AD-related pathology in APP/PS1 mice and the underlying mechanisms. In this study, forty APP/PS1 mice were equally divided into the following 4 groups and treated for 28 days: the chronic sleep deprivation (CSD) group (exposed to sleep deprivation from zeitgeber time [ZT] 0 to ZT 12 each day), the normal sleep and stress exposure (NSS) group (exposed to a stressor from ZT 0 to ZT 12 each day), the acoustic stimulation during wakefulness (ASW) group (exposed to sleep deprivation and 40 Hz acoustic stimulation from ZT 0 to ZT 12 each day) and the acoustic stimulation during sleep (ASS) group (exposed to sleep deprivation from ZT 0 to ZT 12 and 40 Hz acoustic stimulation from ZT 12 to ZT 24 each day). After the intervention, cognition was assessed by behavioural experiments. The amyloid-β burden was analysed by Western blotting, immunofluorescence and enzyme-linked immunosorbent assay. Tau pathology was assessed by Western blotting. Mitochondrial function was evaluated by transmission electron microscopy, Western blotting and fluorescence intensity measurement. We found that the NSS and ASS groups had better cognitive functions than the CSD and ASW groups. The Aβ burden and tau phosphorylation were lower in the NSS and ASS groups than in the CSD and ASW groups. Mitochondrial function was better in the NSS and ASS groups than in the CSD and ASW groups. However, the differences in these parameters between the NSS and ASS groups and between the CSD and ASW groups were not significant. Our findings suggest that acoustic stimulation at a specific frequency during sleep, but not during wakefulness, reduces the amyloid-β burden by inhibiting amyloid beta precursor protein-binding protein 2, hinders tau phosphorylation by blocking glycogen synthase kinase 3 beta, and restores mitochondrial function by elevating mitophagy and promoting mitochondrial biogenesis.

RevDate: 2023-10-03
CmpDate: 2023-10-02

Bader AC, Van Zuylen EM, Handsley-Davis M, et al (2023)

A relational framework for microbiome research with Indigenous communities.

Nature microbiology, 8(10):1768-1776.

Ethical practices in human microbiome research have failed to keep pace with scientific advances in the field. Researchers seeking to 'preserve' microbial species associated with Indigenous groups, but absent from industrialized populations, have largely failed to include Indigenous people in knowledge co-production or benefit, perpetuating a legacy of intellectual and material extraction. We propose a framework centred on relationality among Indigenous peoples, researchers and microbes, to guide ethical microbiome research. Our framework centres accountability to flatten historical power imbalances that favour researcher perspectives and interests to provide space for Indigenous worldviews in pursuit of Indigenous research sovereignty. Ethical inclusion of Indigenous communities in microbiome research can provide health benefits for all populations and reinforce mutually beneficial partnerships between researchers and the public.

RevDate: 2023-10-20

Efremova I, Maslennikov R, Poluektova E, et al (2023)

Gut Dysbiosis and Hemodynamic Changes as Links of the Pathogenesis of Complications of Cirrhosis.

Microorganisms, 11(9):.

The aim was to evaluate the relationship between gut dysbiosis and hemodynamic changes (hyperdynamic circulation) in cirrhosis, and between hemodynamic changes and complications of this disease. This study included 47 patients with cirrhosis. Stool microbiome was assessed using 16S rRNA gene sequencing. Echocardiography with a simultaneous assessment of blood pressure and heart rate was performed to assess systemic hemodynamics. Patients with hyperdynamic circulation had more severe cirrhosis, lower albumin, sodium and prothrombin levels, higher C-reactive protein, aspartate aminotransferase and total bilirubin levels, and higher incidences of portopulmonary hypertension, ascites, overt hepatic encephalopathy, hypoalbuminemia, hypoprothrombinemia, systemic inflammation, and severe hyperbilirubinemia than patients with normodynamic circulation. Patients with hyperdynamic circulation compared with those with normodynamic circulation had increased abundance of Proteobacteria, Enterobacteriaceae, Bacilli, Streptococcaceae, Lactobacillaceae, Fusobacteria, Micrococcaceae, Intestinobacter, Clostridium sensu stricto, Proteus and Rumicoccus, and decreased abundance of Bacteroidetes, Bacteroidaceae, Holdemanella, and Butyrivibrio. The systemic vascular resistance and cardiac output values correlated with the abundance of Proteobacteria, Enterobacteriaceae, Bacilli, Streptococcaceae, Lactobacillaceae, Micrococcaceae, and Fusobacteria. Heart rate and cardiac output value were negatively correlated with the abundance of Bacteroidetes. The mean pulmonary artery pressure value was positively correlated with the abundance of Proteobacteria and Micrococcaceae, and negatively with the abundance of Holdemanella.

RevDate: 2023-10-03

Kovaleva A, Poluektova E, Maslennikov R, et al (2023)

Effect of Rebamipide on the Intestinal Barrier, Gut Microbiota Structure and Function, and Symptom Severity Associated with Irritable Bowel Syndrome and Functional Dyspepsia Overlap: A Randomized Controlled Trial.

Journal of clinical medicine, 12(18):.

Treatment of functional digestive disorders is not always effective. Therefore, a search for new application points for potential drugs is perspective. Our aim is to evaluate the effect of rebamipide on symptom severity, intestinal barrier status, and intestinal microbiota composition and function in patients with diarrheal variant of irritable bowel syndrome overlapping with functional dyspepsia (D-IBSoFD). Sixty patients were randomized to receive trimebutine (TRI group), trimebutine + rebamipide (T + R group), or rebamipide (REB group) for 2 months. At the beginning and end of the study, patients were assessed for general health (SF-36), severity of digestive symptoms (Gastrointestinal Symptom Rating and 7 × 7 scales), state of the intestinal barrier, and composition (16S rRNA gene sequencing) and function (short-chain fatty acid fecal content) of the gut microbiota. The severity of most digestive symptoms was reduced in the REB and T + R groups to levels similar to that observed in the TRI group. The duodenal and sigmoidal lymphocytic and sigmoidal eosinophilic infiltration was decreased only in the REB and T + R groups, not in the TRI group. Serum zonulin levels were significantly decreased only in the REB group. A decrease in intraepithelial lymphocytic infiltration in the duodenum correlated with a decrease in the severity of rumbling and flatulence, while a decrease in infiltration within the sigmoid colon correlated with improved stool consistency and decreased severity of the sensation of incomplete bowel emptying. In conclusion, rebamipide improves the intestinal barrier condition and symptoms in D-IBSoFD. The rebamipide effects are not inferior to those of trimebutine.

RevDate: 2023-10-03
CmpDate: 2023-09-29

Mousa WK, Mousa S, Ghemrawi R, et al (2023)

Probiotics Modulate Host Immune Response and Interact with the Gut Microbiota: Shaping Their Composition and Mediating Antibiotic Resistance.

International journal of molecular sciences, 24(18):.

The consortium of microbes inhabiting the human body, together with their encoded genes and secreted metabolites, is referred to as the "human microbiome." Several studies have established a link between the composition of the microbiome and its impact on human health. This impact spans local gastrointestinal inflammation to systemic autoimmune disorders and neurodegenerative diseases such as Alzheimer's and Autism. Some of these links have been validated by rigorous experiments that identify specific strains as mediators or drivers of a particular condition. Consequently, the development of probiotics to compensate for a missing beneficial microbe(s) has advanced and become popular, especially in the treatment of irritable bowel diseases and to restore disrupted gut flora after antibiotic administration. The widespread use of probiotics is often advocated as a natural ecological therapy. However, this perception is not always accurate, as there is a potential for unexpected interactions when administering live microbial cultures. Here, we designed this research to explore the intricate interactions among probiotics, the host, and microbes through a series of experiments. Our objectives included assessing their immunomodulatory effects, response to oral medications, impact on microbial population dynamics, and mediation of antibiotic resistance. To achieve these goals, we employed diverse experimental protocols, including cell-based enzyme -linked immunosorbent assay (ELISA), antibiotic susceptibility testing, antimicrobial activity assays, computational prediction of probiotic genes responsible for antibiotic resistance, polymerase chain reaction (PCR)-based validation of predicted genes, and survival assays of probiotics in the presence of selected oral medications. Our findings highlight that more than half of the tested probiotics trigger an inflammatory response in the Caco-2 cell line, are influenced by oral medications, exhibit antibacterial activity, and possess genes encoding antimicrobial resistance. These results underscore the necessity for a reevaluation of probiotic usage and emphasize the importance of establishing regulations to govern probiotic testing, approval, and administration.

RevDate: 2023-10-26
CmpDate: 2023-10-23

Blaustein RA, Shen Z, Kashaf SS, et al (2023)

Expanded microbiome niches of RAG-deficient patients.

Cell reports. Medicine, 4(10):101205.

The complex interplay between microbiota and immunity is important to human health. To explore how altered adaptive immunity influences the microbiome, we characterize skin, nares, and gut microbiota of patients with recombination-activating gene (RAG) deficiency-a rare genetically defined inborn error of immunity (IEI) that results in a broad spectrum of clinical phenotypes. Integrating de novo assembly of metagenomes from RAG-deficient patients with reference genome catalogs provides an expansive multi-kingdom view of microbial diversity. RAG-deficient patient microbiomes exhibit inter-individual variation, including expansion of opportunistic pathogens (e.g., Corynebacterium bovis, Haemophilus influenzae), and a relative loss of body site specificity. We identify 35 and 27 bacterial species derived from skin/nares and gut microbiomes, respectively, which are distinct to RAG-deficient patients compared to healthy individuals. Underscoring IEI patients as potential reservoirs for viral persistence and evolution, we further characterize the colonization of eukaryotic RNA viruses (e.g., Coronavirus 229E, Norovirus GII) in this patient population.

RevDate: 2023-10-26

Walker JN, Hanson BM, Hunter T, et al (2023)

A prospective randomized clinical trial to assess antibiotic pocket irrigation on tissue expander breast reconstruction.

Microbiology spectrum, 11(5):e0143023 [Epub ahead of print].

Bacterial infection is the most common complication following staged post-mastectomy breast reconstruction initiated with a tissue expander (TE). To limit bacterial infection, antibiotic irrigation of the surgical site is commonly performed despite little high-quality data to support this practice. We performed a prospective randomized control trial to compare the impact of saline irrigation alone to a triple antibiotic irrigation regimen (1 g cefazolin, 80 mg gentamicin, and 50,000 units of bacitracin in 500 mL of saline) for breast implant surgery. The microbiome in breasts with cancer (n = 16) was compared to those without (n = 16), as all patients (n = 16) had unilateral cancers but bilateral mastectomies (n = 32). Biologic and prosthetic specimens procured both at the time of mastectomy and during TE removal months later were analyzed for longitudinal comparison. Outcomes included clinical infection, bacterial abundance, and relative microbiome composition. No patient in either group suffered a reconstructive failure or developed an infection. Triple antibiotic irrigation administered at the time of immediate TE reconstruction did not reduce bacterial abundance or impact microbial diversity relative to saline irrigation at the time of planned exchange. Implanted prosthetic material adopted the microbial composition of the surrounding host tissue. In cancer-naïve breasts, relative to saline, antibiotic irrigation increased bacterial abundance on periprosthetic capsules (P = 0.03) and acellular dermal matrices (P = 0.04) and altered the microbiota on both. These data show that, relative to saline only, the use of triple antibiotic irrigation in TE breast reconstruction does impact the bacterial abundance and diversity of certain biomaterials from cancer-naïve breasts. IMPORTANCE The lifetime risk of breast cancer is ~13% in women and is treated with a mastectomy in ~50% of cases. The majority are reconstructed, usually starting with a tissue expander to help restore the volume for a subsequent permanent breast implant or the women's own tissues. The biopsychosocial benefits of breast reconstruction, though, can be tempered by a high complication rate of at least 7% but over 30% in some women. Bacterial infection is the most common complication, and can lead to treatment delays, patient physical and emotional distress and escalating health care cost. To limit this risk, plastic surgeons have tried a variety of strategies to limit bacterial infection including irrigating the pocket created after removing the breast implant with antibiotic solutions, but good-quality data are scarce. Herein, we study the value of antibiotics in pocket irrigation using a robust randomized clinical trial design and molecular microbiology approaches.

RevDate: 2023-09-28

Ejtahed HS, Parsa M, B Larijani (2023)

Ethical challenges in conducting and the clinical application of human microbiome research.

Journal of medical ethics and history of medicine, 16:5.

RevDate: 2023-11-09

Hyvönen S, Tapiainen T, Pokka T, et al (2023)

Perinatal and Other Risk Factors for Common Infections in Infancy: A Prospective Cohort Study.

The Pediatric infectious disease journal, 42(12):e447-53 [Epub ahead of print].

OBJECTIVE: Limited data from prospective cohort studies in high-income countries are available on the perinatal risk factors for common infections in children. Our hypothesis was that perinatal factors may be risk factors for infectious episodes during the first year of life.

METHODS: In this prospective Health and Early Life Microbiota birth cohort study of full-term infants (n = 1052) born in 2016-2018, the number and duration of infection episodes were collected online at weekly to monthly intervals. In a multivariate regression model, the main exposures were perinatal factors such as mode of delivery and intrapartum antibiotics. Environmental factors were additional exposures. The outcomes were the number and duration of infectious episodes in the first year of life.

RESULTS: The mean number of infection episodes was 4.2 (2.9 SD). The mean duration of infection symptoms was 44 days (40 SD). Upper respiratory infections accounted for 83% of the episodes (3674/4455). Perinatal factors were not associated with the number nor the duration of infection episodes, but cesarean section was associated with an increased occurrence of urinary tract infections in infancy [adjusted odds ratio (aOR): 3.6; 95% confidence interval (CI): 1.13-11.1]. Of the additional exposures male sex (aOR: 1.1; 95% CI: 1.0-1.2) and the presence of siblings (aOR: 1.3; 95% CI: 1.2-1.4) were associated with the number of infection episodes.

CONCLUSIONS: This prospective cohort study showed that perinatal factors, mode of delivery and intrapartum antibiotics were not associated with the risk of common infections in infancy, but cesarean delivery was associated with a risk of urinary tract infections.

RevDate: 2023-10-20

Roche CE, Montague MJ, Wang J, et al (2023)

Yearly variation coupled with social interactions shape the skin microbiome in free-ranging rhesus macaques.

Microbiology spectrum, 11(5):e0297423 [Epub ahead of print].

While skin microbes are known to mediate human health and disease, there has been minimal research on the interactions between skin microbiota, social behavior, and year-to-year effects in non-human primates-important animal models for translational biomedical research. To examine these relationships, we analyzed skin microbes from 78 rhesus macaques living on Cayo Santiago Island, Puerto Rico. We considered age, sex, and social group membership, and characterized social behavior by assessing dominance rank and patterns of grooming as compared to nonsocial behaviors. To measure the effects of a shifting environment, we sampled skin microbiota (based on sequence analysis of the 16S rRNA V4 region) and assessed weather across sampling periods between 2013 and 2015. We hypothesized that, first, monkeys with similar social behavior and/or in the same social group would possess similar skin microbial composition due, in part, to physical contact, and, second, microbial diversity would differ across sampling periods. We found significant phylum-level differences between social groups in the core microbiome as well as an association between total grooming rates and alpha diversity in the complete microbiome, but no association between microbial diversity and measures of rank or other nonsocial behaviors. We also identified alpha and beta diversity differences in microbiota and differential taxa abundance across two sampling periods. Our findings indicate that social dynamics interact with yearly environmental changes to shape the skin microbiota in rhesus macaques, with potential implications for understanding the factors affecting the microbiome in humans, which share many biological and social characteristics with these animals. IMPORTANCE Primate studies are valuable for translational and evolutionary insights into the human microbiome. The majority of primate microbiome studies focus on the gut, so less is known about the factors impacting the microbes on skin and how their links affect health and behavior. Here, we probe the impact of social interactions and the yearly environmental changes on food-provisioned, free-ranging monkeys living on a small island. We expected animals that lived together and groomed each other would have more similar microbes on their skin, but surprisingly found that the external environment was a stronger influence on skin microbiome composition. These findings have implications for our understanding of the human skin microbiome, including potential manipulations to improve health and treat disease.

RevDate: 2023-09-28

Fiocchi A, Monaci L, De Angelis E, et al (2023)

Reactivity to allergenic food contaminants: A study on products on the market.

Clinical and translational allergy, 13(9):e12301.

BACKGROUND: The frequency and severity of reactions in food-allergic consumers exposed to unintentional food allergen contamination during production is unknown. To warn allergic consumers, it has been suggested for pre-packaged foods to be precautionary labelled when the food allergen contamination may exceed the amount to which 1%-5% of the population could react (ED01-ED05). ED01 for hazelnut and milk have been estimated at 0.1 and 0.2 mg, respectively, by the Voluntary Incidental Trace Allergen Labelling (VITAL) initiative. The respective reference doses recommended by the FAO/WHO Codex consultation are 3 and 2 mg. We evaluated the reactivity to potential traces of milk and hazelnut allergens in allergen-free pre-packaged products by children affected by severe allergies to milk and hazelnuts.

METHODS: Oral Food Challenges with commercially available hazelnut-free wafer biscuits and milk-free chocolate pralines were administered to patients with severe food allergies to hazelnut and cow's milk, respectively. Contamination levels of milk or hazelnut allergens were measured using chromatographic separation interfaced with triple quadrupole mass spectrometry.

RESULTS: No hazelnut allergic patient showed allergic reactions to exposure to biscuits, nor any milk allergic patient displayed allergic reactions to the dark chocolate praline. While no hazelnut trace was detected in biscuits, the praline was found to be contaminated by milk at concentrations ranging between 8 and 35 mg total protein/kg food. In our dose model, these amounts exceeded 1.5-10 times the VITAL ED01 and reached the threshold suggested by the FAO/WHO Codex consultation.

CONCLUSIONS: Upon the consumption of food products available on the market, many patients with severe food allergies tolerate significantly higher doses of allergen than reference doses indicated in the VITAL system used for precautionary allergen labelling. These doses support the safety of the FAO/WHO recommended reference doses.

RevDate: 2023-10-19

Robertson EB, JLE Willett (2023)

Streptococcus mutans inhibits the growth of Enterococcus via the non-ribosomal cyclic peptide mutanobactin.

bioRxiv : the preprint server for biology.

Enterococcus faecalis is a Gram-positive commensal bacterium in the gastrointestinal tract and an opportunistic pathogen. Enterococci are a leading cause of nosocomial infections, treatment of which is complicated by intrinsic and acquired antibiotic resistance mechanisms. Additionally, E. faecalis has been associated with various oral diseases, and it is frequently implicated in the failure of endodontic treatment. For establishment and persistence in a microbial community, E. faecalis must successfully compete against other bacteria. Streptococcal species play an important role in the establishment of the oral microbiome and co-exist with Enterococcus in the small intestine, yet the nature of interactions between E. faecalis and oral streptococci remains unclear. Here, we describe a mechanism by which Streptococcus mutans inhibits the growth of E. faecalis and other Gram-positive pathogens through the production of mutanobactin, a cyclic lipopeptide. Mutanobactin is produced by a polyketide synthase-nonribosomal peptide synthetase hybrid system encoded by the mub locus. Mutanobactin-producing S. mutans inhibits planktonic and biofilm growth of E. faecalis and is also active against other Enterococcus species and Staphylococcus aureus. Mutanobactin damages the cell envelope of E. faecalis, similar to other lipopeptide antibiotics like daptomycin. E. faecalis resistance to mutanobactin is mediated by the virulence factor gelatinase, a secreted metalloprotease. Our results highlight the anti-biofilm potential of the microbial natural product mutanobactin, provide insight into how E. faecalis interacts with other organisms in the human microbiome, and demonstrate the importance of studying E. faecalis dynamics within polymicrobial communities.

RevDate: 2023-09-28
CmpDate: 2023-09-25

Wicaksono WA, Cernava T, Wassermann B, et al (2023)

The edible plant microbiome: evidence for the occurrence of fruit and vegetable bacteria in the human gut.

Gut microbes, 15(2):2258565.

Diversity of the gut microbiota is crucial for human health. However, whether fruit and vegetable associated bacteria contribute to overall gut bacterial diversity is still unknown. We reconstructed metagenome-assembled genomes from 156 fruit and vegetable metagenomes to investigate the prevalence of associated bacteria in 2,426 publicly available gut metagenomes. The microbiomes of fresh fruits and vegetables and the human gut are represented by members in common such as Enterobacterales, Burkholderiales, and Lactobacillales. Exposure to bacteria via fruit and vegetable consumption potentially has a beneficial impact on the functional diversity of gut microbiota particularly due to the presence of putative health-promoting genes for the production of vitamin and short-chain fatty acids. In the human gut, they were consistently present, although at a low abundance, approx. 2.2%. Host age, vegetable consumption frequency, and the diversity of plants consumed were drivers favoring a higher proportion. Overall, these results provide one of the primary links between the human microbiome and the environmental microbiome. This study revealed evidence that fruit and vegetable-derived microbes could be found in the human gut and contribute to gut microbiome diversity.

RevDate: 2023-09-25
CmpDate: 2023-09-25

Cho H, Qu Y, Liu C, et al (2023)

Comprehensive evaluation of methods for differential expression analysis of metatranscriptomics data.

Briefings in bioinformatics, 24(5):.

Understanding the function of the human microbiome is important but the development of statistical methods specifically for the microbial gene expression (i.e. metatranscriptomics) is in its infancy. Many currently employed differential expression analysis methods have been designed for different data types and have not been evaluated in metatranscriptomics settings. To address this gap, we undertook a comprehensive evaluation and benchmarking of 10 differential analysis methods for metatranscriptomics data. We used a combination of real and simulated data to evaluate performance (i.e. type I error, false discovery rate and sensitivity) of the following methods: log-normal (LN), logistic-beta (LB), MAST, DESeq2, metagenomeSeq, ANCOM-BC, LEfSe, ALDEx2, Kruskal-Wallis and two-part Kruskal-Wallis. The simulation was informed by supragingival biofilm microbiome data from 300 preschool-age children enrolled in a study of childhood dental disease (early childhood caries, ECC), whereas validations were sought in two additional datasets from the ECC study and an inflammatory bowel disease study. The LB test showed the highest sensitivity in both small and large samples and reasonably controlled type I error. Contrarily, MAST was hampered by inflated type I error. Upon application of the LN and LB tests in the ECC study, we found that genes C8PHV7 and C8PEV7, harbored by the lactate-producing Campylobacter gracilis, had the strongest association with childhood dental disease. This comprehensive model evaluation offers practical guidance for selection of appropriate methods for rigorous analyses of differential expression in metatranscriptomics. Selection of an optimal method increases the possibility of detecting true signals while minimizing the chance of claiming false ones.

RevDate: 2023-09-23

Dweh TJ, Pattnaik S, JP Sahoo (2023)

Assessing the impact of meta-genomic tools on current cutting-edge genome engineering and technology.

International journal of biochemistry and molecular biology, 14(4):62-75.

Metagenomics is defined as the study of the genome of the total microbiota found in nature and is often referred to as microbial environmental genomics because it entails the examination of a group of genetic components (genomes) from a diverse community of organisms in a particular setting. It is a sub-branch of omics technology that encompasses Deoxyribonucleic Acid (DNA), Ribonucleic acid (DNA), proteins, and various components associated with comprehensive analysis of all aspects of biological molecules in a system-wide manner. Clustered regularly interspaced palindromic repeats and its endonuclease, CRISPR-associated protein which forms a complex called CRISPR-cas9 technology, though it is a different technique used to make precise changes to the genome of an organism, it can be used in conjunction with metagenomic approaches to give a better, rapid, and more accurate description of genomes and sequence reads. There have been ongoing improvements in sequencing that have deepened our understanding of microbial genomes forever. From the time when only a small amount of gene could be sequenced using traditional methods (e.g., "the plus and minus" method developed by Allan and Sanger and the "chemical cleavage" method that is known for its use in the sequencing the phiX174 bacteriophage genome via radio-labeled DNA polymerase-primer in a polymerization reaction aided by polyacrylamide gel) to the era of total genomes sequencing which includes "sequencing-by-ligation" and the "sequencing-by-synthesis" that detects hydrogen ions when new DNA is synthesized (Second Generation) and then Next Generation Sequencing technologies (NGS). With these technologies, the Human Genome Project (HGP) was made possible. The study looks at recent advancements in metagenomics in plants and animals by examining findings from randomly selected research papers. All selected case studies examined the functional and taxonomical analysis of different microbial communities using high-throughput sequencing to generate different sequence reads. In animals, five studies indicated how Zebrafish, Livestock, Poultry, cattle, niches, and the human microbiome were exploited using environmental samples, such as soil and water, to identify microbial communities and their functions. It has also been used to study the microbiome of humans and other organisms, including gut microbiomes. Recent studies demonstrated how these technologies have allowed for faster and more accurate identification of pathogens, leading to improved disease diagnostics. They have also enabled the development of personalized medicine by allowing for the identification of genetic variations that can impact drug efficacy and toxicity. Continued advancements in sequencing techniques and the refinement of CRISPR-Cas9 tools offer even greater potential for transformative breakthroughs in scientific research and applications. On the other hand, metagenomic data are always large and uneasy to handle. The complexity of taxonomical profiling, functional annotation, and mechanisms of complex interaction still needs better bioinformatics tools. Current review focuses on better (e.g., AI-driven algorithms) tools that can predict metabolic pathways and interactions, and manipulate complex data to address potential bias for accurate interpretation.


ESP Quick Facts

ESP Origins

In the early 1990's, Robert Robbins was a faculty member at Johns Hopkins, where he directed the informatics core of GDB — the human gene-mapping database of the international human genome project. To share papers with colleagues around the world, he set up a small paper-sharing section on his personal web page. This small project evolved into The Electronic Scholarly Publishing Project.

ESP Support

In 1995, Robbins became the VP/IT of the Fred Hutchinson Cancer Research Center in Seattle, WA. Soon after arriving in Seattle, Robbins secured funding, through the ELSI component of the US Human Genome Project, to create the original ESP.ORG web site, with the formal goal of providing free, world-wide access to the literature of classical genetics.

ESP Rationale

Although the methods of molecular biology can seem almost magical to the uninitiated, the original techniques of classical genetics are readily appreciated by one and all: cross individuals that differ in some inherited trait, collect all of the progeny, score their attributes, and propose mechanisms to explain the patterns of inheritance observed.

ESP Goal

In reading the early works of classical genetics, one is drawn, almost inexorably, into ever more complex models, until molecular explanations begin to seem both necessary and natural. At that point, the tools for understanding genome research are at hand. Assisting readers reach this point was the original goal of The Electronic Scholarly Publishing Project.

ESP Usage

Usage of the site grew rapidly and has remained high. Faculty began to use the site for their assigned readings. Other on-line publishers, ranging from The New York Times to Nature referenced ESP materials in their own publications. Nobel laureates (e.g., Joshua Lederberg) regularly used the site and even wrote to suggest changes and improvements.

ESP Content

When the site began, no journals were making their early content available in digital format. As a result, ESP was obliged to digitize classic literature before it could be made available. For many important papers — such as Mendel's original paper or the first genetic map — ESP had to produce entirely new typeset versions of the works, if they were to be available in a high-quality format.

ESP Help

Early support from the DOE component of the Human Genome Project was critically important for getting the ESP project on a firm foundation. Since that funding ended (nearly 20 years ago), the project has been operated as a purely volunteer effort. Anyone wishing to assist in these efforts should send an email to Robbins.

ESP Plans

With the development of methods for adding typeset side notes to PDF files, the ESP project now plans to add annotated versions of some classical papers to its holdings. We also plan to add new reference and pedagogical material. We have already started providing regularly updated, comprehensive bibliographies to the ESP.ORG site.

Electronic Scholarly Publishing
961 Red Tail Lane
Bellingham, WA 98226

E-mail: RJR8222 @

Papers in Classical Genetics

The ESP began as an effort to share a handful of key papers from the early days of classical genetics. Now the collection has grown to include hundreds of papers, in full-text format.

Digital Books

Along with papers on classical genetics, ESP offers a collection of full-text digital books, including many works by Darwin (and even a collection of poetry — Chicago Poems by Carl Sandburg).


ESP now offers a much improved and expanded collection of timelines, designed to give the user choice over subject matter and dates.


Biographical information about many key scientists.

Selected Bibliographies

Bibliographies on several topics of potential interest to the ESP community are now being automatically maintained and generated on the ESP site.

ESP Picks from Around the Web (updated 07 JUL 2018 )