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Bibliography on: Microbiome

The Electronic Scholarly Publishing Project: Providing world-wide, free access to classic scientific papers and other scholarly materials, since 1993.


ESP: PubMed Auto Bibliography 17 Sep 2021 at 01:35 Created: 


It has long been known that every multicellular organism coexists with large prokaryotic ecosystems — microbiomes — that completely cover its surfaces, external and internal. Recent studies have shown that these associated microbiomes are not mere contamination, but instead have profound effects upon the function and fitness of the multicellular organism. We now know that all MCEs are actually functional composites, holobionts, composed of more prokaryotic cells than eukaryotic cells and expressing more prokaryotic genes than eukaryotic genes. A full understanding of the biology of "individual" eukaryotes will now depend on an understanding of their associated microbiomes.

Created with PubMed® Query: microbiome[tiab] NOT pmcbook NOT ispreviousversion

Citations The Papers (from PubMed®)


RevDate: 2021-09-15

Anhê FF, Barra NG, Cavallari JF, et al (2021)

Metabolic endotoxemia is dictated by the type of lipopolysaccharide.

Cell reports, 36(11):109691.

Lipopolysaccharides (LPSs) can promote metabolic endotoxemia, which is considered inflammatory and metabolically detrimental based on Toll-like receptor (TLR)4 agonists, such as Escherichia coli-derived LPS. LPSs from certain bacteria antagonize TLR4 yet contribute to endotoxemia measured by endotoxin units (EUs). We found that E. coli LPS impairs gut barrier function and worsens glycemic control in mice, but equal doses of LPSs from other bacteria do not. Matching the LPS dose from R. sphaeroides and E. coli by EUs reveals that only E. coli LPS promotes dysglycemia and adipose inflammation, delays intestinal glucose absorption, and augments insulin and glucagon-like peptide (GLP)-1 secretion. Metabolically beneficial endotoxemia promoted by R. sphaeroides LPS counteracts dysglycemia caused by an equal dose of E. coli LPS and improves glucose control in obese mice. The concept of metabolic endotoxemia should be expanded beyond LPS load to include LPS characteristics, such as lipid A acylation, which dictates the effect of metabolic endotoxemia.

RevDate: 2021-09-15

Levy EI, De Geyter C, Ouald Chaib A, et al (2021)

How to manage irritable bowel syndrome in children.

Acta paediatrica (Oslo, Norway : 1992) [Epub ahead of print].

AIM: This paper discusses the risk factors and management of paediatric irritable bowel syndrome (IBS), with a focus on the role of the gastro-intestinal microbiome.

METHODS: English articles of interest published in PubMed and Google Scholar were searched using subject heading and key words of interest.

RESULTS: Only few randomized controlled trials on the management of IBS in children have been published. The vast majority of these intervention trials target to change the composition of the gastro-intestinal microbiome. Most studies are underpowered. Major heterogeneities in study designs such as differences in inclusion criteria, including patients with different pain-related functional gastrointestinal disorders and differences in primary outcomes make it impossible to formulate recommendations. Overall few adverse events are reported what could indicate safety or point to suboptimal conduction of clinical trials and safety reporting. However, it can also not be excluded that some interventions such as the administration of selected probiotic products may result in benefit.

CONCLUSION: There is insufficient evidence to recommend any therapeutic intervention in paediatric IBS, including manipulation of the gastrointestinal tract microbiome, despite the evidence that dysbiosis seems an associated pathophysiologic factor. More designed prospective trials are needed since IBS is not a rare condition during childhood.

RevDate: 2021-09-15

Kovtonyuk LV, Caiado F, Garcia-Martin S, et al (2021)

IL-1 Mediates Microbiome-Induced Inflamm-Ageing of Hematopoietic Stem Cells in Mice.

Blood pii:476914 [Epub ahead of print].

Ageing is associated with impaired hematopoietic and immune function. This is caused in part by decreased hematopoietic stem cell (HSC) population fitness and an increased myeloid differentiation bias. The reasons for this aging-associated HSC impairment are incompletely understood. We here demonstrate that aged specific pathogen free (SPF) wild-type mice in contrast to young SPF mice produce more IL-1a/b in steady-state bone marrow (BM), with most of IL-1a/b being derived from myeloid BM cells. Further, blood of steady-state aged SPF wild-type mice contains higher levels of microbe associated molecular patterns (MAMPs), specifically TLR4 and TLR8 ligands. Also, BM myeloid cells from aged mice produce more IL-1b in vitro, and aged mice show higher and more durable IL-1a/b responses upon LPS stimulation in vivo. To test if HSC ageing is driven via IL-1a/b, we evaluated HSCs from IL-1 receptor 1 (IL-1R1) knock-out mice. Indeed, aged HSCs from IL-1R1 knock-out mice show significantly mitigated ageing-associated inflammatory signatures. Moreover, HSCs from aged IL-1R1KO and also from germ-free mice maintain unbiased lympho-myeloid hematopoietic differentiation upon transplantation, thus resembling this functionality of young HSCs. Importantly, in vivo antibiotic suppression of microbiota or pharmacologic blockade of IL-1 signaling in aged wild-type mice was similarly sufficient to reverse myeloid biased output of their HSC populations. Collectively, our data defines the microbiome-IL-1/IL-1R1 axis as a key, self-sustaining, but also therapeutically partially reversible driver of HSC inflamm-ageing.

RevDate: 2021-09-15

Zhang K, Zhou X, Qin J, et al (2021)

Dynamic Change in Oral Microbiota of Children With Cleft Lip and Palate After Alveolar Bone Grafting.

The Cleft palate-craniofacial journal : official publication of the American Cleft Palate-Craniofacial Association [Epub ahead of print].

To investigate the longitudinal influence of alveolar bone grafting on the oral microbiota of children with cleft lip and palate (CLP).

Twenty-eight children with nonsyndromic CLP were recruited and underwent secondary alveolar bone grafting at the first time. Unstimulated saliva and plaque samples were collected from the subjects preoperatively and at 2 days, 1 month, and 3 months postoperatively. The v3-v4 hypervariable regions of the 16S rRNA gene from bacterial DNA were sequenced using the Illumina MiSeq sequencing platform.

The alpha diversity of the saliva and plaque microbiota was significantly decreased at 2 days postoperatively and then increased at 1 and 3 months postoperatively. The saliva and plaque microbiota compositions at 2 days postoperatively differed from those at the other time points, and the microbiota compositions at 1 and 3 months postoperatively showed a gradual shift toward the preoperative composition. The saliva, but not plaque, microbiota composition 3 months postoperatively was similar to that preoperatively.

The effect of secondary alveolar bone grafting on the plaque microbiota in children with CLP lasted longer than the saliva microbiota. Alveolar bone grafting altered the saliva microbiota in children with CLP within 3 months postoperatively.

RevDate: 2021-09-15

Chen Y, Qiao L, Song X, et al (2021)

Protective effects of selenium nanoparticle-enriched Lactococcus lactis NZ9000 against enterotoxigenic Escherichia coli K88-induced intestinal barrier damage in mice.

Applied and environmental microbiology [Epub ahead of print].

Composite microecological agents have received widespread attention due to their advantageous properties, including safety, multi-effects, and low cost. This study was conducted to evaluate the protective effects of selenium (Se) nanoparticle-enriched Lactococcus lactis NZ9000 (L. lactis NZ9000-SeNPs) against enterotoxigenic Escherichia coli K88 (ETEC K88)-induced intestinal barrier damage in C57BL/6 mice. Oral administration of L. lactis NZ9000-SeNPs significantly increased the villi height and the number of goblet cells in the ileum, and reduced the levels of serum and ileal interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ), and increased the activities of thioredoxin reductase (TrxR) and glutathione peroxidase (GSH-Px) compared with the ETEC K88-infected group not treated with L. lactis NZ9000-SeNPs. In addition, L. lactis NZ9000-SeNPs significantly attenuated the reduction of the expression levels of occludin and claudin-1, dysbiosis of the gut microbiome, and the activation of toll-like receptor (TLR)/nuclear factor-kappa (NF-κB)-mediated signaling pathway induced by ETEC K88. These findings suggested that L. lactis NZ9000-SeNPs may be a promising and safe Se supplement for food or feed additives. Importance The beneficial effects of microecological agents have been widely proven. Se, which is nutritionally essential trace element for human and animals, is incorporated into selenoproteins that have a wide range of pleiotropic effects, ranging from antioxidant and anti-inflammatory effects. However, the sodium selenite, a common addition form of Se in feed and food, has disadvantages such as strong toxicity and low bioavailability. We investigated the protective effects of L. lactis NZ9000-SeNPs against ETEC K88-induced intestinal barrier injury in C57BL/6 mice. Our results show that L. lactis NZ9000-SeNPs effectively alleviate ETEC-K88-induced intestinal barrier dysfunction. This study highlights the importance of developing a promising and safe Se supplement for the substation of sodium selenite applied in food, feed and biomedicine.

RevDate: 2021-09-15

Wernke KM, Tirla A, Xue M, et al (2021)

Probing Microbiome Genotoxicity: A Stable Colibactin Provides Insight into Structure-Activity Relationships and Facilitates Mechanism of Action Studies.

Journal of the American Chemical Society [Epub ahead of print].

Colibactin is a genotoxic metabolite produced by commensal-pathogenic members of the human microbiome that possess the clb (aka pks) biosynthetic gene cluster. clb+ bacteria induce tumorigenesis in models of intestinal inflammation and have been causally linked to oncogenesis in humans. While colibactin is believed underlie these effects, it has not been possible to study the molecule directly due to its instability. Herein, we report the synthesis and biological studies of colibactin 742 (4), a stable colibactin derivative. We show that colibactin 742 (4) induces DNA interstrand-cross-links, activation of the Fanconi Anemia DNA repair pathway, and G2/M arrest in a manner similar to clb+E. coli. The linear precursor 9, which mimics the biosynthetic precursor to colibactin, also recapitulates the bacterial phenotype. In the course of this work, we discovered a novel cyclization pathway that was previously undetected in MS-based studies of colibactin, suggesting a refinement to the natural product structure and its mode of DNA binding. Colibactin 742 (4) and its precursor 9 will allow researchers to study colibactin's genotoxic effects independent of the producing organism for the first time.

RevDate: 2021-09-15

Mizusawa M, KC Carroll (2021)

The future of Clostridioides difficile diagnostics.

Current opinion in infectious diseases, 34(5):483-490.

PURPOSE OF REVIEW: Although the epidemiology of Clostridioides difficile has changed, this organism continues to cause significant morbidity and mortality. This review addresses current and future approaches to the diagnosis of C. difficile disease.

RECENT FINDINGS: Over the last several years, large prospective studies have confirmed that there is no single optimal test for the diagnosis of C. difficile disease. The pendulum has swung from a focus on rapid molecular diagnosis during the years of the ribotype 027 epidemic, to a call for use of algorithmic approaches that include a test for toxin detection. In addition, diagnostic stewardship has been shown to improve test utilization, especially with molecular methods. Advances in testing include development of ultrasensitive toxin tests and an expansion of biomarkers that may be more C. difficile specific. Microbiome research may be leveraged to inform novel diagnostic approaches based on measurements of volatile and nonvolatile organic compounds in stool.

SUMMARY: As rates of C. difficile infection decline, emphasis is now on improving test utilization and a quest for improved diagnostic approaches. These approaches may involve implementation of technologies that improve toxin testing, predict patients likely to have disease and/or a severe outcome, and harnessing research on changes in the microbiome to advance metabolomics.

RevDate: 2021-09-15

Brycki JD, Chen See JR, Letson GR, et al (2021)

Temporal Transcriptomics of Gut Escherichia coli in Caenorhabditis elegans Models of Aging.

Microbiology spectrum [Epub ahead of print].

Host-bacterial interactions over the course of aging are understudied due to complexities of the human microbiome and challenges of collecting samples that span a lifetime. To investigate the role of host-microbial interactions in aging, we performed transcriptomics using wild-type Caenorhabditis elegans (N2) and three long-lived mutants (daf-2, eat-2, and asm-3) fed Escherichia coli OP50 and sampled at days 5, 7.5, and 10 of adulthood. We found host age is a better predictor of the E. coli expression profiles than host genotype. Specifically, host age was associated with clustering (permutational multivariate analysis of variance [PERMANOVA], P = 0.001) and variation (Adonis, P = 0.001, R2 = 11.5%) among E. coli expression profiles, whereas host genotype was not (PERMANOVA, P > 0.05; Adonis, P > 0.05, R2 = 5.9%). Differential analysis of the E. coli transcriptome yielded 22 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and 100 KEGG genes enriched when samples were grouped by time point [LDA, linear discriminant analysis; log(LDA), ≥2; P ≤ 0.05], including several involved in biofilm formation. Coexpression analysis of host and bacterial genes yielded six modules of C. elegans genes that were coexpressed with one bacterial regulator gene over time. The three most significant bacterial regulators included genes relating to biofilm formation, lipopolysaccharide production, and thiamine biosynthesis. Age was significantly associated with clustering and variation among transcriptomic samples, supporting the idea that microbes are active and plastic within C. elegans throughout life. Coexpression analysis further revealed interactions between E. coli and C. elegans that occurred over time, building on a growing literature of host-microbial interactions. IMPORTANCE Previous research has reported effects of the microbiome on health span and life span of Caenorhabditis elegans, including interactions with evolutionarily conserved pathways in humans. We build on this literature by reporting the gene expression of Escherichia coli OP50 in wild-type (N2) and three long-lived mutants of C. elegans. The manuscript represents the first study, to our knowledge, to perform temporal host-microbial transcriptomics in the model organism C. elegans. Understanding changes to the microbial transcriptome over time is an important step toward elucidating host-microbial interactions and their potential relationship to aging. We found that age was significantly associated with clustering and variation among transcriptomic samples, supporting the idea that microbes are active and plastic within C. elegans throughout life. Coexpression analysis further revealed interactions between E. coli and C. elegans that occurred over time, which contributes to our growing knowledge about host-microbial interactions.

RevDate: 2021-09-15

Wu Z, Han Y, Caporaso JG, et al (2021)

Cigarette Smoking and Opium Use in Relation to the Oral Microbiota in Iran.

Microbiology spectrum [Epub ahead of print].

Cigarettes and opium contain chemicals and particulate matter that may modify the oral microbiota. This study aimed to investigate the association between cigarette and opium use with the oral microbiota. A total of 558 participants were recruited from Iran between 2011 and 2015. Individuals were categorized as never cigarette nor opium users, ever cigarette-only smokers, ever opium-only users, and ever both cigarette and opium users. Participants provided saliva samples for 16S rRNA gene sequencing. Logistic regression, microbiome regression-based kernel association test (MiRKAT), and zero-inflated beta regression models were calculated. For every increase in 10 observed amplicon sequence variants (ASVs), the odds for being a cigarette-only smoker, opium-only user, and both user compared to never users decreased by 9% (odds ratio [OR] = 0.91; 95% confidence interval [95% CI] = 0.86 to 0.97), 13% (OR = 0.87; 95% CI = 0.75 to 1.01), and 12% (OR = 0.88; 95% CI = 0.80 to 0.96), respectively. The microbial communities differed by cigarette and opium use as indicated by MiRKAT models testing the three beta-diversity matrices (P < 0.05 for all). Three genera were less likely and one genus was more likely to be detected in cigarette-only smokers or opium-only users than in never users. The relative abundance of the phylum Actinobacteria (never, 14.78%; both, 21.20%) was higher and the phyla Bacteroidetes (never, 17.63%; both, 11.62%) and Proteobacteria (never, 9.06%; both, 3.70%) were lower in users of both cigarettes and opium, while the phylum Firmicutes (never, 54.29%; opium, 65.49%) was higher in opium-only users. Cigarette and opium use was associated with lower alpha-diversity, overall oral microbiota community composition, and both the presence and relative abundance of multiple taxa. IMPORTANCE Cigarette smoking and opium use are associated with periodontal disease caused by specific bacteria such as Porphyromonas gingivalis, which suggests a link between cigarette smoking and opium use and the oral microbiota. Alterations of the oral microbiota in cigarette smokers compared to nonsmokers have been reported, but this has not been studied across diverse populations. Additionally, the association of opium use with the oral microbiota has not been investigated to date. We conducted this study to investigate differences in the oral microbiota between ever users of cigarettes only, opium only, and both cigarettes and opium and never users of cigarettes and opium in Iran. Lower alpha-diversity, distinct overall oral microbial communities, and the presence and relative abundance of multiple taxa have been found for users of cigarettes and/or opium.

RevDate: 2021-09-15

Guan H, Pu Y, Liu C, et al (2021)

Comparison of Fecal Collection Methods on Variation in Gut Metagenomics and Untargeted Metabolomics.

mSphere [Epub ahead of print].

Integrative analysis of high-quality metagenomics and metabolomics data from fecal samples provides novel clues for the mechanism underpinning gut microbe-human interactions. However, data regarding the influence of fecal collection methods on both metagenomics and metabolomics are sparse. Six fecal collection methods (the gold standard [GS] [i.e., immediate freezing at -80°C with no solution], 95% ethanol, RNAlater, OMNIgene Gut, fecal occult blood test [FOBT] cards, and Microlution) were used to collect 88 fecal samples from eight healthy volunteers for whole-genome shotgun sequencing (WGSS) and untargeted metabolomic profiling. Metrics assessed included the abundances of predominant phyla and α- and β-diversity at the species, gene, and pathway levels. Intraclass correlation coefficients (ICCs) were calculated for microbes and metabolites to estimate (i) stability (day 4 versus day 0 within each method), (ii) concordance (day 0 for each method versus the GS), and (iii) reliability (day 4 for each method versus the GS). For the top 4 phyla and microbial diversity metrics at the species, gene, and pathway levels, generally high stability and reliability were observed for most methods except for 95% ethanol; similar concordances were seen for different methods. For metabolomics data, 95% ethanol showed the highest stability, concordance, and reliability (median ICCs = 0.71, 0.71, and 0.65, respectively). Taken together, OMNIgene Gut, FOBT cards, RNAlater, and Microlution, but not 95% ethanol, were reliable collection methods for gut metagenomic studies. However, 95% ethanol was the best for preserving fecal metabolite profiles. We recommend using separate collecting methods for gut metagenomic sequencing and fecal metabolomic profiling in large population studies. IMPORTANCE The choice of fecal collection method is essential for studying gut microbe-human interactions in large-scale population-based research. In this study, we examined the effects of fecal collection methods and storage time at ambient temperature on variations in the gut microbiome community composition; microbial diversity metrics at the species, gene, and pathway levels; antibiotic resistance genes; and metabolome profiling. Our findings suggest using different fecal sample collection methods for different data generation purposes. OMNIgene Gut, FOBT cards, RNAlater, and Microlution, but not 95% ethanol, were reliable collection methods for gut metagenomic studies. However, 95% ethanol was the best for preserving fecal metabolite profiles.

RevDate: 2021-09-15

Hellmann KT, Tuura CE, Fish J, et al (2021)

Viability-Resolved Metagenomics Reveals Antagonistic Colonization Dynamics of Staphylococcus epidermidis Strains on Preterm Infant Skin.

mSphere [Epub ahead of print].

Preterm infants are at increased risk of infections caused by coagulase-negative staphylococci (CoNS) that colonize skin. Technical barriers in sequencing low-microbial-biomass skin swabs from preterm infants hinder attempts to gain a strain-level understanding of CoNS colonization dynamics within their developing skin microbiome. Here, the microbiome of five skin sites and available stool was studied from four preterm infants hospitalized over their first 2 months of life. We used propidium monoazide treatment of samples to enrich for the viable microbiome and metagenomic shotgun sequencing to resolve species and strains. The microbiome of different skin sites overlapped with each other, was dominated by the CoNS species Staphylococcus epidermidis and Staphylococcus capitis, and was distinct from stool. Species diversity on skin increased over time despite antibiotic exposure. Evidence of antagonism between the most common S. epidermidis strains, ST2 and ST59, included negative relationships for species correlation networks and in situ replication rates and that ST2 colonized skin earlier but was often replaced by ST59 over time. Experiments done with reference isolates showed that ST2 produced more biofilm than ST59 on plastic surfaces, which was reduced in mixed culture. We also discovered that a rare S. epidermidis strain, ST5, grew rapidly in stool in association with Stenotrophomonas maltophilia from a suspected episode of infection. Viability treatment of samples and moderate throughput shotgun sequencing provides strain-level information about CoNS colonization dynamics of preterm infant skin that ultimately might be exploited to prevent infections. IMPORTANCE The skin is a habitat for microbes that commonly infect preterm infants, but the use of sequencing for fine-scale study of the microbial communities of skin that develop in these infants has been limited by technical barriers. We treated skin swabs of preterm infants with a photoreactive dye that eliminates DNA from nonviable microbes and then sequenced the remaining DNA. We found that two strains of the most common species, Staphylococcus epidermidis, showed an antagonistic relationship on skin by cooccurring with different species, replicating fastest in different samples, and dominating skin sites at different times. Representatives of these strains also differed in their ability to stick to plastic surfaces-an important pathogenicity trait of this species. Our study shows the feasibility of gaining detailed information about strain colonization dynamics from this difficult-to-sequence body site of preterm infants, which might be used to guide novel approaches to prevent infections.

RevDate: 2021-09-15

Zhang S, Wu P, Tian Y, et al (2021)

Gut Microbiota Serves a Predictable Outcome of Short-Term Low-Carbohydrate Diet (LCD) Intervention for Patients with Obesity.

Microbiology spectrum [Epub ahead of print].

To date, much progress has been made in dietary therapy for obese patients. A low-carbohydrate diet (LCD) has reached a revival in its clinical use during the past decade with undefined mechanisms and debatable efficacy. The gut microbiota has been suggested to promote energy harvesting. Here, we propose that the gut microbiota contributes to the inconsistent outcome under an LCD. To test this hypothesis, patients with obesity or patients who were overweight were randomly assigned to a normal diet (ND) or an LCD group with ad libitum energy intake for 12 weeks. Using matched sampling, the microbiome profile at baseline and end stage was examined. The relative abundance of butyrate-producing bacteria, including Porphyromonadaceae Parabacteroides and Ruminococcaceae Oscillospira, was markedly increased after LCD intervention for 12 weeks. Moreover, within the LCD group, participants with a higher relative abundance of Bacteroidaceae Bacteroides at baseline exhibited a better response to LCD intervention and achieved greater weight loss outcomes. Nevertheless, the adoption of an artificial neural network (ANN)-based prediction model greatly surpasses a general linear model in predicting weight loss outcomes after LCD intervention. Therefore, the gut microbiota served as a positive outcome predictor and has the potential to predict weight loss outcomes after short-term LCD intervention. Gut microbiota may help to guide the clinical application of short-term LCD intervention to develop effective weight loss strategies. (This study has been registered at the China Clinical Trial Registry under approval no. ChiCTR1800015156). IMPORTANCE Obesity and its related complications pose a serious threat to human health. Short-term low-carbohydrate diet (LCD) intervention without calorie restriction has a significant weight loss effect for overweight/obese people. Furthermore, the relative abundance of Bacteroidaceae Bacteroides is a positive outcome predictor of individual weight loss after short-term LCD intervention. Moreover, leveraging on these distinct gut microbial structures at baseline, we have established a prediction model based on the artificial neural network (ANN) algorithm that could be used to estimate weight loss potential before each clinical trial (with Chinese patent number 2021104655623). This will help to guide the clinical application of short-term LCD intervention to improve weight loss strategies.

RevDate: 2021-09-15

Kushak RI, Sengupta A, HS Winter (2021)

Interactions between the intestinal microbiota and epigenome in individuals with autism spectrum disorder.

Developmental medicine and child neurology [Epub ahead of print].

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by variable impairment of cognitive function and interpersonal relationships. Furthermore, some individuals with ASD have gastrointestinal disorders that have been correlated with impairments in intestinal microbiota. Gut microbiota are important not only for intestinal health, but also for many other functions including food digestion, energy production, immune system regulation, and, according to current data, behavior. Disruption of the indigenous microbiota, microbial dysbiosis (imbalance between microorganisms present in the gut), overgrowth of potentially pathogenic microorganisms, a less diverse microbiome, or lower levels of beneficial bacteria in children with ASD can affect behavior. Metabolome analysis in children with ASD has identified perturbations in multiple metabolic pathways that might be associated with cognitive functions. Recent studies have shown that the intestinal microbiome provides environmental signals that can modify host response to stimuli by modifying the host epigenome, which affects DNA methylation, histone modification, and non-coding RNAs. The most studied microbiota-produced epigenetic modifiers are short-chain fatty acids, although other products of intestinal microbiota might also cause epigenetic modifications in the host's DNA. Here we review evidence suggesting that epigenetic alterations caused by modification of gene expression play an important role in understanding ASD.

RevDate: 2021-09-15

Gershon MD, KG Margolis (2021)

The gut, its microbiome, and the brain: connections and communications.

The Journal of clinical investigation, 131(18):.

Modern research on gastrointestinal behavior has revealed it to be a highly complex bidirectional process in which the gut sends signals to the brain, via spinal and vagal visceral afferent pathways, and receives sympathetic and parasympathetic inputs. Concomitantly, the enteric nervous system within the bowel, which contains intrinsic primary afferent neurons, interneurons, and motor neurons, also senses the enteric environment and controls the detailed patterns of intestinal motility and secretion. The vast microbiome that is resident within the enteric lumen is yet another contributor, not only to gut behavior, but to the bidirectional signaling process, so that the existence of a microbiota-gut-brain "connectome" has become apparent. The interaction between the microbiota, the bowel, and the brain now appears to be neither a top-down nor a bottom-up process. Instead, it is an ongoing, tripartite conversation, the outline of which is beginning to emerge and is the subject of this Review. We emphasize aspects of the exponentially increasing knowledge of the microbiota-gut-brain "connectome" and focus attention on the roles that serotonin, Toll-like receptors, and macrophages play in signaling as exemplars of potentially generalizable mechanisms.

RevDate: 2021-09-15

Gao YX, Li X, Zhao JR, et al (2021)

Response of microbial communities based on full-scale classification and antibiotic resistance genes to azithromycin and copper combined pollution in activated sludge nitrification laboratory mesocosms at low temperature.

Bioresource technology, 341:125859 pii:S0960-8524(21)01200-1 [Epub ahead of print].

This study aimed to investigate the short-term response of abundant-rare genera and antibiotic resistance genes (ARGs) to azithromycin (AZM, 0.05-40 mg/L) and copper (1 mg/L) combined pollution in activated sludge nitrification system at low temperature. Nitrification was as expected inhibited in stress- and post-effects periods under AZM concentration higher than 5 mg/L. Abundant and rare taxa presented dissimilar responses based on full-scale classification. Conditionally rare or abundant taxa (CRAT) were keystone taxa. Relative abundance of ammonia-oxidizing archaea increased, and three aerobic denitrifying bacteria (Brevundimonas, Comamonas and Trichococcus) were enriched (from 9.83% to 68.91% in total). Ammonia nitrogen assimilating into Org-N and denitrification may be nitrogen pathways based on predict analysis. 29 ARGs were found with more co-occurrence patterns and high concentration of AZM (greater than 5 mg/L) caused their proliferation. Importantly, expect for some abundant taxa, rare taxa, potential pathogens and nitrogen-removal functional genera were the main potential hosts of ARGs.

RevDate: 2021-09-15

Trego AC, Conall Holohan B, Keating C, et al (2021)

First proof of concept for full-scale, direct, low-temperature anaerobic treatment of municipal wastewater.

Bioresource technology, 341:125786 pii:S0960-8524(21)01127-5 [Epub ahead of print].

Municipal wastewater constitutes the largest fraction of wastewater, and yet treatment processes are largely removal-based. High-rate anaerobic digestion (AD) has revolutionised the sustainability of industrial wastewater treatment and could additionally provide an alternative for municipal wastewater. While AD of dilute municipal wastewater is common in tropical regions, the low temperatures of temperate climates has resulted in slow uptake. Here, we demonstrate for the first time, direct, high-rate, low-temperature AD of low-strength municipal wastewater at full-scale. An 88 m3 hybrid reactor was installed at the municipal wastewater treatment plant in Builth Wells, UK and operated for 290 days. Ambient temperatures ranged from 2 to 18 °C, but remained below 15 °C for > 100 days. Influent BOD fluctuated between 2 and 200 mg L-1. However, BOD removal often reached > 85%. 16S rRNA amplicon sequencing of DNA from the biomass revealed a highly adaptable core microbiome. These findings could provide the basis for the next-generation of municipal wastewater treatment.

RevDate: 2021-09-15

Liu C, Cheung WH, Li J, et al (2021)

Understanding the gut microbiota and sarcopenia: a systematic review.

Journal of cachexia, sarcopenia and muscle [Epub ahead of print].

BACKGROUND: Gut microbiota dysbiosis and sarcopenia commonly occur in the elderly. Although the concept of the gut-muscle axis has been raised, the casual relationship is still unclear. This systematic review analyses the current evidence of gut microbiota effects on muscle/sarcopenia.

METHODS: A systematic review was performed in PubMed, Embase, Web of Science, and The Cochrane Library databases using the keywords (microbiota* OR microbiome*) AND (sarcopen* OR muscle). Studies reporting the alterations of gut microbiota and muscle/physical performance were analysed.

RESULTS: A total of 26 pre-clinical and 10 clinical studies were included. For animal studies, three revealed age-related changes and relationships between gut microbiota and muscle. Three studies focused on muscle characteristics of germ-free mice. Seventy-five per cent of eight faecal microbiota transplantation studies showed that the recipient mice successfully replicated the muscle phenotype of donors. There were positive effects on muscle from seven probiotics, two prebiotics, and short-chain fatty acids (SCFAs). Ten studies investigated on other dietary supplements, antibiotics, exercise, and food withdrawal that affected both muscle and gut microbiota. Twelve studies explored the potential mechanisms of the gut-muscle axis. For clinical studies, 6 studies recruited 676 elderly people (72.8 ± 5.6 years, 57.8% female), while 4 studies focused on 244 young adults (29.7 ± 7.8 years, 55.4% female). The associations of gut microbiota and muscle had been shown in four observational studies. Probiotics, prebiotics, synbiotics, fermented milk, caloric restriction, and exercise in six studies displayed inconsistent effects on muscle mass, function, and gut microbiota.

CONCLUSIONS: Altering the gut microbiota through bacteria depletion, faecal transplantation, and various supplements was shown to directly affect muscle phenotypes. Probiotics, prebiotics, SCFAs, and bacterial products are potential novel therapies to enhance muscle mass and physical performance. Lactobacillus and Bifidobacterium strains restored age-related muscle loss. Potential mechanisms of microbiome modulating muscle mainly include protein, energy, lipid, and glucose metabolism, inflammation level, neuromuscular junction, and mitochondrial function. The role of the gut microbiota in the development of muscle loss during aging is a crucial area that requires further studies for translation to patients.

RevDate: 2021-09-15

Willing CE, Pierroz G, Guzman A, et al (2021)

Keep your friends close: Host compartmentalisation of microbial communities facilitates decoupling from effects of habitat fragmentation.

Root-associated fungal communities modify the climatic niches and even the competitive ability of their hosts, yet how the different components of the root microbiome are modified by habitat loss remains a key knowledge gap. Using principles of landscape ecology, we tested how free-living versus host-associated microbes differ in their response to landscape heterogeneity. Further, we explore how compartmentalisation of microbes into specialised root structures filters for key fungal symbionts. Our study demonstrates that free-living fungal community structure correlates with landscape heterogeneity, but that host-associated fungal communities depart from these patterns. Specifically, biotic filtering in roots, especially via compartmentalisation within specialised root structures, decouples the biogeographic patterns of host-associated fungal communities from the soil community. In this way, even as habitat loss and fragmentation threaten fungal diversity in the soils, plant hosts exert biotic controls to ensure associations with critical mutualists, helping to preserve the root mycobiome.

RevDate: 2021-09-15

Zhang YG, Xia Y, J Sun (2021)

A simple and sensitive method to detect vitamin D receptor expression in various disease models using stool samples.

Genes & diseases, 8(6):939-945 pii:S2352-3042(20)30044-1.

Vitamin D receptor (VDR) executes the main biological functions of its ligand vitamin D. VDR/vitamin D plays critical roles in regulating host immunity, maintaining barrier functions, and shaping gut microbiome. Reduction of intestinal VDR has been reported in various diseases, including inflammatory diseases and colon cancer. However, it is always challenging to get biopsies to test the pathologic changes of VDR in intestine. In the current study, we reported a simple and sensitive quantitative PCR (qPCR) method to detect reduction of intestinal VDR using fecal samples. We validated this method in several experimental models, such as colitis, bacterial infection, and aging. We further correlated the qPCR data of VDR with the protein level of VDR in colon or serum 25 (OH)D3 in mice with different VDR status (VDR+/+, VDR+/-, and VDR-/-). Our data indicate that the qPCR method to test VDR using fecal samples could detect the expression level of intestinal VDR in various diseases. Our study highlights the feasibility, sensitivity, and simplicity of a molecular method to study the status of VDR as a biomarker.

RevDate: 2021-09-15

Huang X, Pan T, Yan L, et al (2021)

The inflammatory microenvironment and the urinary microbiome in the initiation and progression of bladder cancer.

Genes & diseases, 8(6):781-797 pii:S2352-3042(20)30127-6.

Accumulating evidence suggests that chronic inflammation may play a critical role in various malignancies, including bladder cancer. This hypothesis stems in part from inflammatory cells observed in the urethral microenvironment. Chronic inflammation may drive neoplastic transformation and the progression of bladder cancer by activating a series of inflammatory molecules and signals. Recently, it has been shown that the microbiome also plays an important role in the development and progression of bladder cancer, which can be mediated through the stimulation of chronic inflammation. In effect, the urinary microbiome can play a role in establishing the inflammatory urethral microenvironment that may facilitate the development and progression of bladder cancer. In other words, chronic inflammation caused by the urinary microbiome may promote the initiation and progression of bladder cancer. Here, we provide a detailed and comprehensive account of the link between chronic inflammation, the microbiome and bladder cancer. Finally, we highlight that targeting the urinary microbiome might enable the development of strategies for bladder cancer prevention and personalized treatment.

RevDate: 2021-09-15

Patel P, Poudel A, Kafle S, et al (2021)

Influence of Microbiome and Antibiotics on the Efficacy of Immune Checkpoint Inhibitors.

Cureus, 13(8):e16829.

The human microbiome mainly consists of bacteria and interacts closely with the immune system. Immune checkpoint inhibitors (ICI) are used to treat several types of cancers. Recently, it has been identified that the gut microbiome plays a role in the effectiveness of immunotherapy. This study aims to analyze the effect of microbiome and antibiotics on the effectiveness of ICI in cancer patients and the measures to improve efficacy based on that. A detailed review was conducted on articles published in PubMed and Science Direct in the last five years i.e., 2016 to 2021. A total of 16 articles involving 1293 patients with cancer who were receiving immunotherapy, were deemed eligible to be included in the final review. Data were extracted from the eligible articles and were checked for quality appraisal. All 16 articles revealed the effect of either gut microbiome or antibiotics or both on ICI. Based on our findings, we found that the microbiome enriched in different microorganisms responded differently to the ICI and that antibiotics negatively impacted the effectiveness of ICI. The time at which patients receiving ICI were prescribed antibiotics influenced the effect of ICI. Antibiotics and different microbiome also affected progression-free survival (PFS) and overall survival (OS).

RevDate: 2021-09-15

Ham J, Kim J, Choi S, et al (2021)

Interactions between NCR+ILC3s and the Microbiome in the Airways Shape Asthma Severity.

Immune network, 21(4):e25.

Asthma is a heterogeneous disease whose development is shaped by a variety of environmental and genetic factors. While several recent studies suggest that microbial dysbiosis in the gut may promote asthma, little is known about the relationship between the recently discovered lung microbiome and asthma. Innate lymphoid cells (ILCs) have also been shown recently to participate in asthma. To investigate the relationship between the lung microbiome, ILCs, and asthma, we recruited 23 healthy controls (HC), 42 patients with non-severe asthma, and 32 patients with severe asthma. Flow cytometry analysis showed severe asthma associated with fewer natural cytotoxicity receptor (NCR)+ILC3s in the lung. Similar changes in other ILC subsets, macrophages, and monocytes were not observed. The asthma patients did not differ from the HC in terms of the alpha and beta-diversity of the lung and gut microbiomes. However, lung function correlated positively with both NCR+ILC3 frequencies and microbial diversity in the lung. Sputum NCR+ILC3 frequencies correlated positively with lung microbiome diversity in the HC, but this relationship was inversed in severe asthma. Together, these data suggest that airway NCR+ILC3s may contribute to a healthy commensal diversity and normal lung function.

RevDate: 2021-09-15

Sun G, Xia T, Wei Q, et al (2021)

Analysis of gut microbiota in three species belonging to different genera (Hemitragus, Pseudois, and Ovis) from the subfamily Caprinae in the absence of environmental variance.

Ecology and evolution, 11(17):12129-12140 pii:ECE37976.

This study aimed to identify the effects of host species on the gut microbial flora in three species (Hemitragus jemlahicus, Pseudois nayaur, and Ovis orientalis) from the subfamily Caprinae, by excluding the impact of environment factors. We investigated the differences in intestinal flora of three species belonging to Caprinae, which were raised in identical conditions. Fecal samples were collected from tahr, mouflon, and bharal, and the V3-V4 region of the 16S ribosomal RNA gene was analyzed by high-throughput sequencing. The analysis of 16S rRNA gene sequences reveals that fecal samples were mainly composed of four phyla: Firmicutes, Bacteroidetes, Spirochaetes, and Proteobacteria. The most abundant phyla included Firmicutes and Bacteroidetes accounting for >90% of the bacteria, and a higher Firmicutes/Bacteroidetes ratio was observed in tahrs. Moreover, significant differences existed at multiple levels of classifications in the relative abundance of intestinal flora, differing greatly between species. Phylogenetic analyses based on 16S rRNA gene indicated that mouflon is closely related to bharal, and it is inconsistent with previous reports in the species evolutionary relationships. In this study, we demonstrated that the gut microbiota in tahr had a stronger ability to absorb and store energy from the diet compared with mouflon and bharal, and the characteristics of host-microbiome interactions were not significant.

RevDate: 2021-09-15

Fodelianakis S, Washburne AD, Bourquin M, et al (2021)

Microdiversity characterizes prevalent phylogenetic clades in the glacier-fed stream microbiome.

The ISME journal [Epub ahead of print].

Glacier-fed streams (GFSs) are extreme and rapidly vanishing ecosystems, and yet they harbor diverse microbial communities. Although our understanding of the GFS microbiome has recently increased, we do not know which microbial clades are ecologically successful in these ecosystems, nor do we understand potentially underlying mechanisms. Ecologically successful clades should be more prevalent across GFSs compared to other clades, which should be reflected as clade-wise distinctly low phylogenetic turnover. However, methods to assess such patterns are currently missing. Here we developed and applied a novel analytical framework, "phyloscore analysis", to identify clades with lower spatial phylogenetic turnover than other clades in the sediment microbiome across twenty GFSs in New Zealand. These clades constituted up to 44% and 64% of community α-diversity and abundance, respectively. Furthermore, both their α-diversity and abundance increased as sediment chlorophyll a decreased, corroborating their ecological success in GFS habitats largely devoid of primary production. These clades also contained elevated levels of putative microdiversity than others, which could potentially explain their high prevalence in GFSs. This hitherto unknown microdiversity may be threatened as glaciers shrink, urging towards further genomic and functional exploration of the GFS microbiome.

RevDate: 2021-09-15

Hu D, Lu Y, Wang D, et al (2021)

Glycosaminoglycan biosynthesis pathway in host genome is associated with Helicobacter pylori infection.

Scientific reports, 11(1):18235.

Helicobacter pylori is a causative pathogen of many gastric and extra-gastric diseases. It has infected about half of the global population. There were no genome-wide association studies (GWAS) for H. pylori infection conducted in Chinese population, who carried different and relatively homogenous strain of H. pylori. In this work, we performed SNP (single nucleotide polymorphism)-based, gene-based and pathway-based genome-wide association analyses to investigate the genetic basis of host susceptibility to H. pylori infection in 480 Chinese individuals. We also profiled the composition and function of the gut microbiota between H. pylori infection cases and controls. We found several genes and pathways associated with H. pylori infection (P < 0.05), replicated one previously reported SNP rs10004195 in TLR1 gene region (P = 0.02). We also found that glycosaminoglycan biosynthesis related pathway was associated with both onset and progression of H. pylori infection. In the gut microbiome association study, we identified 2 species, 3 genera and several pathways had differential abundance between H. pylori infected cases and controls. This paper is the first GWAS for H. pylori infection in Chinese population, and we combined the genetic and microbial data to comprehensively discuss the basis of host susceptibility to H. pylori infection.

RevDate: 2021-09-15

Andersen AL, Houlind MB, Nielsen RL, et al (2021)

Optimization of Nutrition And Medication (OptiNAM) for acutely admitted older patients: protocol for a randomized single-blinded controlled trial.

Trials, 22(1):616.

BACKGROUND: Internationally, older patients (≥65 years) account for more than 40% of acute admissions. Older patients admitted to the emergency department (ED) are frequently malnourished and exposed to inappropriate medication prescribing, due in part to the inaccuracy of creatinine-based equations for estimated glomerular filtration rate (eGFR). The overall aims of this trial are to investigate: (1) the efficacy of a medication review (MED intervention) independent of nutritional status, (2) the accuracy of eGFR equations based on various biomarkers compared to measured GFR (mGFR) based on 99mTechnetium-diethylenetriaminepentaacetic acid plasma clearance, and (3) the efficacy of an individualized multimodal and transitional nutritional intervention (MULTI-NUT-MED intervention) in older patients with or at risk of malnutrition in the ED.

METHODS: The trial is a single-center block randomized, controlled, observer-blinded, superiority and explorative trial with two parallel groups. The population consists of 200 older patients admitted to the ED: 70 patients without malnutrition or risk of malnutrition and 130 patients with or at risk of malnutrition defined as a Mini Nutritional Assessment-Short Form score ≤11. All patients without the risk of malnutrition receive the MED intervention, which consists of a medication review by a pharmacist and geriatrician in the ED. Patients with or at risk of malnutrition receive the MULTI-NUT-MED intervention, which consists of the MED intervention in addition to, dietary counseling and individualized interventions based on the results of screening tests for dysphagia, problems with activities of daily living, low muscle strength in the lower extremities, depression, and problems with oral health. Baseline data are collected upon study inclusion, and follow-up data are collected at 8 and 16 weeks after discharge. The primary outcomes are (1) change in medication appropriateness index (MAI) score from baseline to 8 weeks after discharge, (2) accuracy of different eGFR equations compared to mGFR, and (3) change in health-related quality of life (measured with EuroQol-5D-5L) from baseline to 16 weeks after discharge.

DISCUSSION: The trial will provide new information on strategies to optimize the treatment of malnutrition and inappropriate medication prescribing among older patients admitted to the ED.

TRAIL REGISTRATION: NTC03741283 . Retrospectively registered on 14 November 2018.

RevDate: 2021-09-15

Song XR, Xu Y, Seng DJ, et al (2021)

[Advances in adenotonsillar microbiome].

Zhonghua er bi yan hou tou jing wai ke za zhi = Chinese journal of otorhinolaryngology head and neck surgery, 56(8):885-890.

RevDate: 2021-09-14

Saccà ML, LM Manici (2021)

Honey bee-associated bacteria as producers of bioactive compounds for protecting hives. A biosynthetic gene-based approach.

Microbiological research, 252:126860 pii:S0944-5013(21)00166-X [Epub ahead of print].

Honey bee-associated bacteria are a source of natural compounds of interest for controlling hive decline which is threatening bee health globally. Genes involved in the biosynthesis of a series of extracellular compounds released by bacteria living on the external surface of honey bees were investigated. A biosynthetic gene-based approach was adopted by developing a battery of primers to target the genes involved in the biosynthesis of four groups of bioactive compounds (pyrrolizidine alkaloids, surfactin, 2-heptanone and helveticin J). The primers were tested on 51 bacterial isolates belonging to Bacillus thuringiensis, Acetobacteraceae bacterium, Bifidobacterium asteroides and Apilactobacillus kunkeei. The developed primers led to species-specific detection and characterization of the functional genes involved in the production of three out of four groups of compounds selected for this study. The findings suggest that microbial populations inhabiting apiaries harbor genes involved in the biosynthesis of metabolites linked to the reduction of important honey bee pathogens such as Varroa destructor, Paenibacillus larvae and Nosema ceranae. The gene-based approach adopted for evaluating the biosynthetic potential of bioactive compounds in hives is promising for investigating further compounds for low input control strategies of bee enemies.

RevDate: 2021-09-14

Martchenko SE, Martchenko A, Biancolin AD, et al (2021)

L-cell Arntl is required for rhythmic glucagon-like peptide-1 secretion and maintenance of intestinal homeostasis.

Molecular metabolism pii:S2212-8778(21)00187-3 [Epub ahead of print].

OBJECTIVES: Recent studies using whole-body clock-disrupted animals identified a disruption in the circadian rhythm of the intestinal L-cell incretin hormone, glucagon-like peptide-1 (GLP-1). Although GLP-1 plays an essential role in metabolism, through enhancement of both glucose-stimulated insulin secretion and satiety, recent evidenced has also demonstrated its importance in regulating intestinal and microbial homeostasis. Therefore, using in vivo and in vitro models, this study assessed the requirement for the core circadian clock gene Arntl in the regulation of GLP-1 secretion and its impact on the intestinal environment.

METHODS: Oral glucose tolerance tests were conducted at zeitgeber 2 and 14 in control and inducible Gcg-Arntl knockout (KO) mice. Colonic intraepithelial lymphocytes were isolated, mucosal gene expression analysis was conducted, and 16S rRNA gene sequencing of colonic feces as well as analysis of microbial metabolites were performed. Time-dependent GLP-1 secretion and transcriptomic analysis were conducted in murine (m) GLUTag L-cells following siRNA-mediated knockdown of Arntl.

RESULTS: Gcg-Arntl KO mice displayed disrupted rhythmic release of GLP-1 associated with reduced secretion at the established peak time point. Analysis of the intestinal environment in KO mice revealed a decreased proportion of CD4+ intraepithelial lymphocytes in association with increased proinflammatory cytokine gene expression and increased colonic weight. Moreover, increased Actinobacteria within the colonic microbiome was found following L-cell Arntl disruption, in association with reductions in the microbial products, short chain fatty acids and bile acids. Finally, siRNA-mediated knockdown of Arntl in mGLUTag L-cells resulted in impaired time-dependent GLP-1 secretion, as well as disruption of pathways related to key cellular processes.

CONCLUSIONS: These data establish, for the first time, the essential role of Arntl in the intestinal L-cell for the regulation of time-dependent GLP-1 secretion. Furthermore, this study revealed an integral role for L-cell Arntl in mediating the intestinal environment which may, ultimately, provide novel insight into the development of therapeutics for the treatment intestinal and metabolic disorders.

RevDate: 2021-09-14

Yan L, Tang L, Zhou Z, et al (2021)

Metagenomics reveals contrasting energy utilization efficiencies of captive and wild camels (Camelus ferus).

Integrative zoology [Epub ahead of print].

Captive conditions can affect the symbiotic microbiome of animals. In this study, we compared the structural and functional differences of the gastrointestinal microbiomes of wild Bactrian camels (Camelus ferus) between wild and captive populations, as well as their different host energy utilization performances through metagenomics. The results showed that wild-living camels harbored more microbial taxa related to the production of volatile fatty acids, fewer methanogens, and fewer genes encoding enzymes involved in methanogenesis, leading to higher energy utilization efficiency compared to that of captive-living camels. These findings suggest that the wild-living camel fecal microbiome demonstrates a series of adaptive characteristics that enable the host to adjust to a relatively barren field environment. Our study provides novel insights into the mechanisms of wildlife adaptations to habitats from the perspective of the microbiome. This article is protected by copyright. All rights reserved.

RevDate: 2021-09-14

Jalili-Firoozinezhad S, Bein A, Gazzaniga FS, et al (2022)

Establishment of a Modular Anaerobic Human Intestine Chip.

Methods in molecular biology (Clifton, N.J.), 2373:69-85.

It is impossible to analyze human-specific host-microbiome interactions using animal models and existing in vitro methods fail to support survival of human cells in direct contact with complex living microbiota for extended times. Here we describe a protocol for culturing human organ-on-a-chip (Organ Chip) microfluidic devices lined by human patient-derived primary intestinal epithelium in the presence of a physiologically relevant transluminal hypoxia gradient that enables their coculture with hundreds of different living aerobic and anaerobic bacteria found within the human gut microbiome. This protocol can be adapted to provide different levels of oxygen tension to facilitate coculturing of microbiome from different regions of gastrointestinal tract, and the same system can be applied with any other type of Organ Chip. This method can help to provide further insight into the host-microbiome interactions that contribute to human health and disease, enable discovery of new microbiome-related diagnostics and therapeutics, and provide a novel approach to advanced personalized medicine.

RevDate: 2021-09-14

Selwal KK, Selwal MK, Z Yu (2021)

Mucolytic bacteria: prevalence in various pathological diseases.

World journal of microbiology & biotechnology, 37(10):176.

All mucins are highly glycosylated and a key constituent of the mucus layer that is vigilant against pathogens in many organ systems of animals and humans. The viscous layer is organized in bilayers, i.e., an outer layer that is loosely arranged, variable in thickness, home to the commensal microbiota that grows in the complex environment, and an innermost layer that is stratified, non-aspirated, firmly adherent to the epithelial cells and devoid of any microorganisms. The O-glycosylation moiety represents the site of adhesion for pathogens and due to the increase of motility, mucolytic activity, and upregulation of virulence factors, some microorganisms can circumvent the component of the mucus layer and cause disruption in organ homeostasis. A dysbiotic microbiome, defective mucus barrier, and altered immune response often result in various diseases. In this review, paramount emphasis is given to the role played by the bacterial species directly or indirectly involved in mucin degradation, alteration in mucus secretion or its composition or mucin gene expression, which instigates many diseases in the digestive, respiratory, and other organ systems. A systematic view can help better understand the etiology of some complex disorders such as cystic fibrosis, ulcerative colitis and expand our knowledge about mucin degraders to develop new therapeutic approaches to correct ill effects caused by these mucin-dwelling pathogens.

RevDate: 2021-09-14

Zhu HZ, Jiang MZ, Zhou N, et al (2021)

Submerged macrophytes recruit unique microbial communities and drive functional zonation in an aquatic system.

Applied microbiology and biotechnology [Epub ahead of print].

Aquatic and wetland systems are widely used for landscapes and water regeneration. Microbiomes and submerged macrophytes (hydrophytes) play essential roles in conversions of organic and inorganic compounds in those ecosystems. The systems were extensively investigated for microbial diversities and compositions. However, little is known about how hydrophytes recruited diverse microbiota and affected functional zonation in aquatic systems. To address this issue, epiphytic leaf and root, sediment, and surrounding water samples were collected from the dragon-shape aquatic system in Beijing Olympic Park. Metagenomic DNAs were extracted and subjected to sequencing. Results showed that epiphytic leaf and root microbiomes and metabolic marker genes were remarkably different from that of surrounding environment. Twenty indicator bacterial genera for epiphytic microbiomes were identified and 50 metabolic marker genes were applied to evaluate the function of epiphytic leaf and root, water, and sediment microbiomes. Co-occurrence analysis revealed highly modularized pattern of metabolic marker genes and indicator bacterial genera related to metabolic functions. These results suggested that hydrophytes shaped microbiomes and drove functional zonation in aquatic systems. KEY POINTS: • Microbiomes of hydrophytes and their surrounding environments were investigated. • Twenty indicator bacterial genera highly specific to epiphytic biofilms were identified. • Epiphytes recruited unique microbiomes and drove functional zonation in aquatic systems.

RevDate: 2021-09-14

Hoffman C, Siddiqui NY, Fields I, et al (2021)

Species-Level Resolution of Female Bladder Microbiota from 16S rRNA Amplicon Sequencing.

mSystems [Epub ahead of print].

The human bladder contains bacteria, even in the absence of infection. Interest in studying these bacteria and their association with bladder conditions is increasing. However, the chosen experimental method can limit the resolution of the taxonomy that can be assigned to the bacteria found in the bladder. 16S rRNA amplicon sequencing is commonly used to identify bacteria in urinary specimens, but it is typically restricted to genus-level identification. Our primary aim here was to determine if accurate species-level identification of bladder bacteria is possible using 16S rRNA amplicon sequencing. We evaluated the ability of different classification schemes, each consisting of combinations of a reference database, a 16S rRNA gene variable region, and a taxonomic classification algorithm to correctly classify bladder bacteria. We show that species-level identification is possible and that the reference database chosen is the most important component, followed by the 16S variable region sequenced. IMPORTANCE Accurate species-level identification from culture-independent techniques is of importance for microbial niches that are less well characterized, such as that of the bladder. 16S rRNA amplicon sequencing, a common culture-independent way to identify bacteria, is often critiqued for lacking species-level resolution. Here, we extensively evaluate classification schemes for species-level bacterial annotation of 16S amplicon data from bladder bacteria. Our results show that the proper choice of taxonomic database and variable region of the 16S rRNA gene sequence makes species level identification possible. We also show that this improvement can be achieved through the more careful application of existing methods and resources. Species-level information may deepen our understanding of associations between bacteria in the bladder and bladder conditions such as lower urinary tract symptoms and urinary tract infections.

RevDate: 2021-09-14

Ho B, Ryback D, Benson B, et al (2021)

Gut Metabolites Are More Predictive of Disease and Cohoused States than Gut Bacterial Features in a Polycystic Ovary Syndrome-Like Mouse Model.

mSystems [Epub ahead of print].

Polycystic ovary syndrome (PCOS) impacts ∼10% of reproductive-aged women worldwide. In addition to infertility, women with PCOS suffer from metabolic dysregulation which increases their risk of developing type 2 diabetes, cardiovascular disease, and nonalcoholic fatty liver disease. Studies have shown differences in the gut microbiome of women with PCOS compared to controls, a pattern replicated in PCOS-like mouse models. Recently, using a letrozole (LET)-induced mouse model of PCOS, we demonstrated that cohousing was protective against development of metabolic and reproductive phenotypes and showed via 16S amplicon sequencing that this protection correlated with time-dependent shifts in gut bacteria. Here, we applied untargeted metabolomics and shotgun metagenomics approaches to further analyze the longitudinal samples from the cohousing experiment. Analysis of beta diversity found that untargeted metabolites had the strongest correlation to both disease and cohoused states and that shifts in metabolite diversity were detected prior to shifts in bacterial diversity. In addition, log2 fold analyses found numerous metabolite features, particularly bile acids (BAs), to be highly differentiated between placebo and LET, as well as LET cohoused with placebo versus LET. Our results indicate that changes in gut metabolites, particularly BAs, are associated with a PCOS-like phenotype as well as with the protective effect of cohousing. Our results also suggest that transfer of metabolites via coprophagy occurs rapidly and may precipitate changes in bacterial diversity. This study joins a growing body of research linking changes in primary and secondary BAs to host metabolism and gut microbes relevant to the pathology of PCOS. IMPORTANCE Using a combination of untargeted metabolomics and metagenomics, we performed a comparative longitudinal analysis of the feces collected in a cohousing study with a PCOS-like mouse model. Our results showed that gut metabolite composition experienced earlier and more pronounced differentiation in both the disease model and cohoused mice compared with the microbial composition. Notably, statistical and machine learning approaches identified shifts in the relative abundance of primary and secondary BAs, which have been implicated as modifiers of gut microbial growth and diversity. Network correlation analysis showed strong associations between particular BAs and bacterial species, particularly members of Lactobacillus, and that these correlations were time and treatment dependent. Our results provide novel insights into host-microbe relationships related to hyperandrogenism in females and indicate that focused research into small-molecule control of gut microbial diversity and host physiology may provide new therapeutic options for the treatment of PCOS.

RevDate: 2021-09-14

Diener C, Qin S, Zhou Y, et al (2021)

Baseline Gut Metagenomic Functional Gene Signature Associated with Variable Weight Loss Responses following a Healthy Lifestyle Intervention in Humans.

mSystems [Epub ahead of print].

Recent human feeding studies have shown how the baseline taxonomic composition of the gut microbiome can determine responses to weight loss interventions. However, the functional determinants underlying this phenomenon remain unclear. We report a weight loss response analysis on a cohort of 105 individuals selected from a larger population enrolled in a commercial wellness program, which included healthy lifestyle coaching. Each individual in the cohort had baseline blood metabolomics, blood proteomics, clinical labs, dietary questionnaires, stool 16S rRNA gene sequencing data, and follow-up data on weight change. We generated additional targeted proteomics data on obesity-associated proteins in blood before and after intervention, along with baseline stool metagenomic data, for a subset of 25 individuals who showed the most extreme weight change phenotypes. We built regression models to identify baseline blood, stool, and dietary features associated with weight loss, independent of age, sex, and baseline body mass index (BMI). Many features were independently associated with baseline BMI, but few were independently associated with weight loss. Baseline diet was not associated with weight loss, and only one blood analyte was associated with changes in weight. However, 31 baseline stool metagenomic functional features, including complex polysaccharide and protein degradation genes, stress-response genes, respiration-related genes, and cell wall synthesis genes, along with gut bacterial replication rates, were associated with weight loss responses after controlling for age, sex, and baseline BMI. Together, these results provide a set of compelling hypotheses for how commensal gut microbiota influence weight loss outcomes in humans. IMPORTANCE Recent human feeding studies have shown how the baseline taxonomic composition of the gut microbiome can determine responses to dietary interventions, but the exact functional determinants underlying this phenomenon remain unclear. In this study, we set out to better understand interactions between baseline BMI, metabolic health, diet, gut microbiome functional profiles, and subsequent weight changes in a human cohort that underwent a healthy lifestyle intervention. Overall, our results suggest that the microbiota may influence host weight loss responses through variable bacterial growth rates, dietary energy harvest efficiency, and immunomodulation.

RevDate: 2021-09-14

Leclerc M, Bedu-Ferrari C, Etienne-Mesmin L, et al (2021)

Nitric Oxide Impacts Human Gut Microbiota Diversity and Functionalities.

mSystems [Epub ahead of print].

The disruption of gut microbiota homeostasis has been associated with numerous diseases and with a disproportionate inflammatory response, including overproduction of nitric oxide (NO) in the intestinal lumen. However, the influence of NO on the human gut microbiota has not been well characterized yet. We used in vitro fermentation systems inoculated with human fecal samples to monitor the effect of repetitive NO pulses on the gut microbiota. NO exposure increased the redox potential and modified the fermentation profile and gas production. The overall metabolome was modified, reflecting less strict anaerobic conditions and shifts in amino acid and nitrogen metabolism. NO exposure led to a microbial shift in diversity with a decrease in Clostridium leptum group and Faecalibacterium prausnitzii biomass and an increased abundance of the Dialister genus. Escherichia coli, Enterococcus faecalis, and Proteus mirabilis operational taxonomic unit abundance increased, and strains from those species isolated after NO stress showed resistance to high NO concentrations. As a whole, NO quickly changed microbial fermentations, functions, and composition in a pulse- and dose-dependent manner. NO could shift, over time, the trophic chain to conditions that are unfavorable for strict anaerobic microbial processes, implying that a prolonged or uncontrolled inflammation has detrimental and irreversible consequences on the human microbiome. IMPORTANCE Gut microbiota dysbiosis has been associated with inflammatory diseases. The human inflammatory response leads to an overproduction of nitric oxide (NO) in the gut. However, so far, the influence of NO on the human gut microbiota has not been characterized. In this study, we used in vitro fermentation systems with human fecal samples to understand the effect of NO on the microbiota: NO modified the microbial composition and its functionality. High NO concentration depleted the microbiota of beneficial butyrate-producing species and favored potentially deleterious species (E. coli, E. faecalis, and P. mirabilis), which we showed can sustain high NO concentrations. Our work shows that NO may participate in the vicious circle of inflammation, leading to detrimental and irreversible consequences on human health.

RevDate: 2021-09-14

Handakumbura PP, Rivas Ubach A, AK Battu (2021)

Visualizing the Hidden Half: Plant-Microbe Interactions in the Rhizosphere.

mSystems [Epub ahead of print].

Plant roots and the associated rhizosphere constitute a dynamic environment that fosters numerous intra- and interkingdom interactions, including metabolite exchange between plants and soil mediated by root exudates and the rhizosphere microbiome. These interactions affect plant fitness and performance, soil health, and the belowground carbon budget. Exploring and understanding the molecular mechanisms governing ecosystem responses via rhizosphere interactions allow the rational and sustainable design of future ecosystems. However, visualizing the plant root system architecture with spatially resolved root exudate and microbiome profiles along the root in its native state remains an ambitious grand challenge in rhizosphere biology. To address this challenge, we developed a three-dimensional (3D) root cartography platform to accurately visualize molecular and microbial constituents and their interactions in the root-rhizosphere zone.

RevDate: 2021-09-14

Chen P, Huang J, Rao L, et al (2021)

Resistance and Resilience of Fish Gut Microbiota to Silver Nanoparticles.

mSystems [Epub ahead of print].

Understanding mechanisms governing the resistance and resilience of microbial communities is essential for predicting their ecological responses to environmental disturbances. Although we have a good understanding of such issues for soil and lake ecosystems, how ecological resistance and resilience regulate the microbiota in the fish gut ecosystem remains unclear. Using the zebrafish model, we clarified the potential mechanisms governing the gut microbiota after exposure to silver nanoparticles (AgNPs). Here, we explored the ecological resistance and resilience of gut microbiota in zebrafish exposed to different concentrations of AgNPs (i.e., 10, 33 and 100 μg/liter) for 15, 45, 75 days. The high-throughput sequencing analysis of the 16S rRNA gene showed that AgNP exposure significantly reduced the α-diversity of gut microbiota and resulted in obvious dynamics of community composition and structure. However, the rebound of zebrafish gut microbiota was pushed toward an alternative state after 15 days of AgNP exposure. We found that homogeneous selection was a more prevalent contributor in driving gut community recovery after AgNP exposure. The resilience and resistance of gut microbiota responses to AgNP disturbance might be mainly determined by the predominant keystone taxa such as Acinetobacter and Gemmata. This study not only expanded our understanding of fish gut microbiota's responses to pollutants but also provided new insights into maintaining host-microbiome stability during environmental perturbations. IMPORTANCE Understanding the ecological mechanisms governing the resistance and resilience of microbial communities is a key issue to predict their responses to environmental disturbances. Using the zebrafish model, we wanted to clarify the potential mechanisms governing the resistance and resilience of gut microbiota after exposure to silver nanoparticles (AgNPs). We found that AgNP contamination significantly reduced the α-diversity of gut microbiota and resulted in obvious changes in community composition. The resilience and resistance of gut microbiota to AgNPs might be associated with the predominant keystone taxa (e.g., Acinetobacter and Gemmata). This study greatly expanded our understanding of how fish gut microbiota responds to environmental perturbations and maintains stability.

RevDate: 2021-09-14

Quinn RA, Hagiwara KA, Liu K, et al (2021)

Bridging the Gap between Analytical and Microbial Sciences in Microbiome Research.

mSystems [Epub ahead of print].

Metabolites from the microbiome influence human, animal, and environmental health, but the diversity and functional roles of these compounds have only begun to be elucidated. Comprehensively characterizing these molecules are significant challenges, as it requires expertise in analytical methods, such as mass spectrometry and nuclear magnetic resonance spectroscopy, skills that not many traditional microbiologists or microbial ecologists possess. This creates a gap between microbiome scientists that want to understand the role of microbial metabolites in microbiome systems and the skills required to generate and interpret complex metabolomics data sets. To bridge this gap, microbiome scientists should engage analytical chemists to best understand the underlying chemical principles of the data. Conversely, analytical scientists are encouraged to engage with microbiome scientists to better understand the biological questions being asked with metabolomics and to best communicate its intricacies. Better communication across the chemistry/biology disciplines will further reveal the "dark matter" within microbiomes that maintain healthy humans and environments.

RevDate: 2021-09-14

Rubio-Portillo E, Martin-Cuadrado AB, Ramos-Esplá AÁ, et al (2021)

Metagenomics Unveils Posidonia oceanica "Banquettes" as a Potential Source of Novel Bioactive Compounds and Carbohydrate Active Enzymes (CAZymes).

mSystems [Epub ahead of print].

Posidonia oceanica is a long-living and very slow-growing marine seagrass endemic to the Mediterranean Sea. It produces large amounts of leaf material and rhizomes, which can reach the shore and build important banks known as "banquettes." In recent years, interest in the potential uses of these P. oceanica banquettes has increased, and it was demonstrated that biomass extracts showed antioxidant, antifungal, and antiviral activities. The discovery of new compounds through the culture of microorganisms is limited, and to overcome this limitation, we performed a metagenomic study to investigate the microbial community associated with P. oceanica banquettes. Our results showed that the microbial community associated with P. oceanica banquettes was dominated by Alphaproteobacteria, Gammaproteobacteria, Bacteroidetes, and Cyanobacteria. Pseudoalteromonas was the dominant genus, followed by Alteromonas, Labrenzia, and Aquimarina. The metagenome reads were binned and assembled into 23 nearly complete metagenome-assembled genomes (MAGs), which belonged to new families of Cyanobacteria, Myxococcota, and Granulosicoccaceae and also to the novel genus recently described as Gammaproteobacteria family UBA10353. A comparative analysis with 60 published metagenomes from different environments, including seawater, marine biofilms, soils, corals, sponges, and hydrothermal vents, indicated that banquettes have numbers of natural products and carbohydrate active enzymes (CAZymes) similar to those found for soils and were only surpassed by marine biofilms. New proteins assigned to cellulosome modules and lignocellulose-degrading enzymes were also found. These results unveiled the diverse microbial composition of P. oceanica banquettes and determined that banquettes are a potential source of bioactive compounds and novel enzymes. IMPORTANCE Posidonia oceanica is a long-living and very slow-growing marine seagrass endemic to the Mediterranean Sea that forms large amounts of leaf material and rhizomes, which can reach the shore and build important banks known as "banquettes." These banquettes accumulate on the shore, where they can prevent erosion, although they also cause social concern due to their impact on beach use. Furthermore, Posidonia dry material has been considered a source of traditional remedies in several areas of the Mediterranean, and a few studies have been carried out to explore pharmacological activities of Posidonia extracts. The work presented here provides the first characterization of the microbiome associated with Posidonia banquettes. We carried out a metagenomic analysis together with an in-depth comparison of the banquette metagenome with 60 published metagenomes from different environments. This comparative analysis has unveiled the potential that Posidonia banquettes have for the synthesis of natural products, both in abundance (only surpassed by marine biofilms) and novelty. These products include mainly nonribosomal peptides and carbohydrate active enzymes. Thus, the interest of our work lies in the interest of Posidonia "waste" material as a source of new bioactive compounds and CAZymes.

RevDate: 2021-09-14

Conover AE, Morando M, Zhao Y, et al (2021)

Alphaproteobacteria facilitate Trichodesmium community trimethylamine utilization.

Environmental microbiology [Epub ahead of print].

In the surface waters of the warm oligotrophic ocean, filaments and aggregated colonies of the nitrogen (N)-fixing cyanobacterium Trichodesmium create microscale nutrient-rich oases. These hotspots fuel primary productivity and harbor a diverse consortium of heterotrophs. Interactions with associated microbiota can affect the physiology of Trichodesmium, often in ways that have been predicted to support its growth. Recently, it was found that trimethylamine (TMA), a globally-abundant organic N compound, inhibits N2 fixation in cultures of Trichodesmium without impairing growth rate, suggesting that Trichodesmium receives nitrogen from TMA. In this study, 15 N-TMA DNA stable isotope probing (SIP) of a Trichodesmium enrichment was employed to further investigate TMA metabolism and determine if TMA-N is incorporated directly or secondarily via cross-feeding facilitated by microbial associates. Herein, we identify two members of the marine Roseobacter clade (MRC) of Alphaproteobacteria as the likely metabolizers of TMA and provide genomic evidence that they converted TMA into a more readily available form of N, e.g., NH4 + , which was subsequently used by Trichodesmium and the rest of the community. The results implicate microbiome-mediated carbon (C) and N transformations in modulating N2 fixation, and thus highlight the involvement of host-associated heterotrophs in global biogeochemical cycling. This article is protected by copyright. All rights reserved.

RevDate: 2021-09-14

O'Leary K (2021)

A compelling microbial SagA.

RevDate: 2021-09-14

Odogwu NM, Onebunne CA, Chen J, et al (2021)

Lactobacillus crispatus thrives in pregnancy hormonal milieu in a Nigerian patient cohort.

Scientific reports, 11(1):18152.

Steroid hormones are one of the presumed modulators of Lactobacillus abundance in the vaginal epithelium. We set out to characterize the vaginal microbiome (VMB) and also provide an in-depth understanding of the relative contribution of estradiol (E2) and progesterone (P1) in shaping the vaginal microbiome of Nigerian women (n = 38) who experienced both uncomplicated term delivery and preterm delivery using samples longitudinally collected during pregnancy (17-21, 27-31, 36-41 weeks gestation) and 6 weeks postpartum. Vaginal swabs and blood samples were aseptically collected. Vaginal swabs were used for microbiome assessment using 16S ribosomal RNA (rRNA) gene sequencing. Blood samples were used for hormonal measurement using a competitive-based enzyme-linked immunosorbent assay (ELISA). Across several maternal covariates, maternal age, pregnancy status and delivery mode were not significantly associated with the vaginal microbiota whereas maternal E2 level (pE2 = 0.006, Omnibus), and P1 level (pP1 = 0.001, Omnibus) were significantly associated with the vaginal microbiome. E2 and P1 concentrations increased throughout pregnancy commensurately with increasing proportions of L. crispatus (pE2 = 0.036, pP1 = 0.034, Linear Mixed Model). An increasing trend of α-diversity was also observed as pregnancy progressed (pobserved ASV = 0.006, LMM). A compositional microbiome shift from Lactobacillus profile to non-Lactobacillus profile was observed in most postnatal women (pCST IV < 0.001, LMM). Analysis of our data shows a species-specific link between pregnancy steroid hormone concentration and L. crispatus abundance.

RevDate: 2021-09-14

Walls Castellanos M, EC Claud (2021)

The microbiome, guard or threat to infant health.

Trends in molecular medicine pii:S1471-4914(21)00228-8 [Epub ahead of print].

Despite improvements in survival for very low birthweight (VLBW) premature infants, there continues to be significant morbidity for these infants at remarkable cost to the healthcare system. Concurrent development of the preterm infant intestine alongside the gut microbiome in the clinical setting rather than in the protected in utero environment where it would usually occur creates significant vulnerabilities for the infant's immature intestine and immune system, resulting in devastating illness and neurological injury. However, the microbiome also has the capacity to promote healthy development. Studies of parallel gut microbiome and preterm infant development have given key insight into the impact of the microbiome on intestinal as well as neural development and may provide potential therapeutic targets to prevent preterm infant morbidities.

RevDate: 2021-09-14

Zhang W, T Pan (2021)

Quantitative probing of glycosylated queuosine modifications in tRNA.

Methods in enzymology, 658:73-82.

Queuosine (Q) in humans is a microbiome-dependent modification in the wobble anticodon position of tRNATyr, tRNAHis, tRNAAsn, and tRNAAsp. These tRNAs share a G34U35N36 anticodon consensus. In humans, the Q base in tRNATyr and tRNAAsp is further glycosylated to generate galactosyl-Q (galQ) and mannosyl-Q (manQ) modifications. Q-tRNA modification is known to regulate translation in a codon dependent manner, but the function of Q glycosylation is unknown. A sensitive and quantitative detection method for Q-glycosylation in tRNA is essential to investigate its biological function. Although LC/MS was used in the characterization of glyco-Q tRNA, the requirements of large amount of input material and LC/MS expertise limit its application. We recently developed an acid denaturing gel and Northern blot method to sensitively detect galQ and manQ-tRNA modification and quantify their modification fractions using just microgram amounts of total RNA. This method uses the same acid denaturing gel system for separating charged from uncharged tRNA; however, deacylated, galQ and manQ modified tRNAs are also separated from unmodified tRNAs because of the positive charge carried by the secondary amine and the large chemical moiety of the glyco-Q base. Our method enables rapid investigation of glycosylated Q modification in tRNA, and also has the potential to investigate other large tRNA modifications that carry a positive charge under acid denaturing gel conditions.

RevDate: 2021-09-14

Smith DRM, Temime L, L Opatowski (2021)

Microbiome-pathogen interactions drive epidemiological dynamics of antibiotic resistance: a modelling study applied to nosocomial pathogen control.

eLife, 10: pii:68764 [Epub ahead of print].

The human microbiome can protect against colonization with pathogenic antibiotic-resistant bacteria (ARB), but its impacts on the spread of antibiotic resistance are poorly understood. We propose a mathematical modelling framework for ARB epidemiology formalizing within-host ARB-microbiome competition, and impacts of antibiotic consumption on microbiome function. Applied to the healthcare setting, we demonstrate a trade-off whereby antibiotics simultaneously clear bacterial pathogens and increase host susceptibility to their colonization, and compare this framework with a traditional strain-based approach. At the population level, microbiome interactions drive ARB incidence, but not resistance rates, reflecting distinct epidemiological relevance of different forces of competition. Simulating a range of public health interventions (contact precautions, antibiotic stewardship, microbiome recovery therapy) and pathogens (Clostridioides difficile, methicillin-resistant Staphylococcus aureus, multidrug-resistant Enterobacteriaceae) highlights how species-specific within-host ecological interactions drive intervention efficacy. We find limited impact of contact precautions for Enterobacteriaceae prevention, and a promising role for microbiome-targeted interventions to limit ARB spread.

RevDate: 2021-09-14

Shute A, Callejas BE, Li S, et al (2021)

Cooperation between host immunity and the gut bacteria is essential for helminth-evoked suppression of colitis.

Microbiome, 9(1):186.

BACKGROUND: Studies on the inhibition of inflammation by infection with helminth parasites have, until recently, overlooked a key determinant of health: the gut microbiota. Infection with helminths evokes changes in the composition of their host's microbiota: one outcome of which is an altered metabolome (e.g., levels of short-chain fatty acids (SCFAs)) in the gut lumen. The functional implications of helminth-evoked changes in the enteric microbiome (composition and metabolites) are poorly understood and are explored with respect to controlling enteric inflammation.

METHODS: Antibiotic-treated wild-type, germ-free (GF) and free fatty-acid receptor-2 (ffar2) deficient mice were infected with the tapeworm Hymenolepis diminuta, then challenged with DNBS-colitis and disease severity and gut expression of the il-10 receptor-α and SCFA receptors/transporters assessed 3 days later. Gut bacteria composition was assessed by 16 s rRNA sequencing and SCFAs were measured. Other studies assessed the ability of feces or a bacteria-free fecal filtrate from H. diminuta-infected mice to inhibit colitis.

RESULTS: Protection against disease by infection with H. diminuta was abrogated by antibiotic treatment and was not observed in GF-mice. Bacterial community profiling revealed an increase in variants belonging to the families Lachnospiraceae and Clostridium cluster XIVa in mice 8 days post-infection with H. diminuta, and the transfer of feces from these mice suppressed DNBS-colitis in GF-mice. Mice treated with a bacteria-free filtrate of feces from H. diminuta-infected mice were protected from DNBS-colitis. Metabolomic analysis revealed increased acetate and butyrate (both or which can reduce colitis) in feces from H. diminuta-infected mice, but not from antibiotic-treated H. diminuta-infected mice. H. diminuta-induced protection against DNBS-colitis was not observed in ffar2-/- mice. Immunologically, anti-il-10 antibodies inhibited the anti-colitic effect of H. diminuta-infection. Analyses of epithelial cell lines, colonoids, and colon segments uncovered reciprocity between butyrate and il-10 in the induction of the il-10-receptor and butyrate transporters.

CONCLUSION: Having defined a feed-forward signaling loop between il-10 and butyrate following infection with H. diminuta, this study identifies the gut microbiome as a critical component of the anti-colitic effect of this helminth therapy. We suggest that any intention-to-treat with helminth therapy should be based on the characterization of the patient's immunological and microbiological response to the helminth.

RevDate: 2021-09-14

Damico ME, Rueppell O, Shaffer Z, et al (2021)

High royal jelly production does not impact the gut microbiome of honey bees.

Animal microbiome, 3(1):60.

BACKGROUND: Honey bees are not only essential for pollination services, but are also economically important as a source of hive products (e.g., honey, royal jelly, pollen, wax, and propolis) that are used as foods, cosmetics, and alternative medicines. Royal jelly is a popular honey bee product with multiple potential medicinal properties. To boost royal jelly production, a long-term genetic selection program of Italian honey bees (ITBs) in China has been performed, resulting in honey bee stocks (here referred to as RJBs) that produce an order of magnitude more royal jelly than ITBs. Although multiple studies have investigated the molecular basis of increased royal jelly yields, one factor that has not been considered is the role of honey bee-associated gut microbes.

RESULTS: Based on the behavioral, morphological, physiological, and neurological differences between RJBs and ITBs, we predicted that the gut microbiome composition of RJBs bees would differ from ITBs. To test this hypothesis, we investigated the bacterial composition of RJB and ITB workers from an urban location and RJBs from a rural location in China. Based on 16S rRNA gene profiling, we did not find any evidence that RJBs possess a unique bacterial gut community when compared to ITBs. However, we observed differences between honey bees from the urban versus rural sites.

CONCLUSIONS: Our results suggest that the environmental factors rather than stock differences are more important in shaping the bacterial composition in honey bee guts. Further studies are needed to investigate if the observed differences in relative abundance of taxa between the urban and rural bees correspond to distinct functional capabilities that impact honey bee health. Because the lifestyle, diet, and other environmental variables are different in rural and urban areas, controlled studies are needed to determine which of these factors are responsible for the observed differences in gut bacterial composition between urban and rural honeybees.

RevDate: 2021-09-14

Gupta VK, Cunningham KY, Hur B, et al (2021)

Gut microbial determinants of clinically important improvement in patients with rheumatoid arthritis.

Genome medicine, 13(1):149.

BACKGROUND: Rapid advances in the past decade have shown that dysbiosis of the gut microbiome is a key hallmark of rheumatoid arthritis (RA). Yet, the relationship between the gut microbiome and clinical improvement in RA disease activity remains unclear. In this study, we explored the gut microbiome of patients with RA to identify features that are associated with, as well as predictive of, minimum clinically important improvement (MCII) in disease activity.

METHODS: We conducted a retrospective, observational cohort study on patients diagnosed with RA between 1988 and 2014. Whole metagenome shotgun sequencing was performed on 64 stool samples, which were collected from 32 patients with RA at two separate time-points approximately 6-12 months apart. The Clinical Disease Activity Index (CDAI) of each patient was measured at both time-points to assess achievement of MCII; depending on this clinical status, patients were distinguished into two groups: MCII+ (who achieved MCII; n = 12) and MCII- (who did not achieve MCII; n = 20). Multiple linear regression models were used to identify microbial taxa and biochemical pathways associated with MCII while controlling for potentially confounding factors. Lastly, a deep-learning neural network was trained upon gut microbiome, clinical, and demographic data at baseline to classify patients according to MCII status, thereby enabling the prediction of whether a patient will achieve MCII at follow-up.

RESULTS: We found age to be the largest determinant of the overall compositional variance in the gut microbiome (R2 = 7.7%, P = 0.001, PERMANOVA). Interestingly, the next factor identified to explain the most variance in the gut microbiome was MCII status (R2 = 3.8%, P = 0.005). Additionally, by looking at patients' baseline gut microbiome profiles, we observed significantly different microbiome traits between patients who eventually showed MCII and those who did not. Taxonomic features include alpha- and beta-diversity measures, as well as several microbial taxa, such as Coprococcus, Bilophila sp. 4_1_30, and Eubacterium sp. 3_1_31. Notably, patients who achieved clinical improvement had higher alpha-diversity in their gut microbiomes at both baseline and follow-up visits. Functional profiling identified fifteen biochemical pathways, most of which were involved in the biosynthesis of L-arginine, L-methionine, and tetrahydrofolate, to be differentially abundant between the MCII patient groups. Moreover, MCII+ and MCII- groups showed significantly different fold-changes (from baseline to follow-up) in eight microbial taxa and in seven biochemical pathways. These results could suggest that, depending on the clinical course, gut microbiomes not only start at different ecological states, but also are on separate trajectories. Finally, the neural network proved to be highly effective in predicting which patients will achieve MCII (balanced accuracy = 90.0%, leave-one-out cross-validation), demonstrating potential clinical utility of gut microbiome profiles.

CONCLUSIONS: Our findings confirm the presence of taxonomic and functional signatures of the gut microbiome associated with MCII in RA patients. Ultimately, modifying the gut microbiome to enhance clinical outcome may hold promise as a future treatment for RA.

RevDate: 2021-09-13

Chai Y, Luo J, Y Bao (2021)

Effects of Polygonatum sibiricum saponin on hyperglycemia, gut microbiota composition and metabolic profiles in type 2 diabetes mice.

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 143:112155 pii:S0753-3322(21)00939-2 [Epub ahead of print].

Diabetes is a global disease that endangers human health. As reported, saponins are effective bioactive compounds for treating type 2 diabetes mellitus (T2DM) and have nontoxic side effects. This study aimed to examine the hypoglycemic effects of Polygonatum sibiricum saponin (PSS) on T2DM mice. We found that PSS could significantly decrease the levels of insulin secretion and fasting blood glucose (FBG) in T2DM mice. And the level of triacylglycerol (TG), total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) in the blood was decreased. In contrast, the content of high-density lipoprotein cholesterol (HDL-C) was increased. 16S rDNA sequencing was used to evaluate the changes in the gut microbiota of T2DM mice, and metabolites were analyzed by metabolomic profiling. The results showed that PSS could decrease the abundance of Firmicutes in T2DM mice, increase the abundance of Bacteroidetes. It also increased the abundance of some bacterial genera (Lactobacillus, Lachnospiraceae_NK4A136_group and Intestinimonas). The phenotypes of the gut microbiome also changed accordingly. Metabolomics analysis showed that carbohydrate metabolism and amino acid metabolisms, such as L-alanine and L-glutamic acid, were greatly affected by PSS. In addition, the levels of inositol and chlorogenic acid in metabolites also increased significantly under PSS intervention. In general, PSS could exert its hypoglycemic effect, regulate the gut microbiota and affect the metabolism of T2DM mice.

RevDate: 2021-09-13

Heymann CJF, Bard JM, Heymann MF, et al (2021)

The intratumoral microbiome: Characterization methods and functional impact.

Cancer letters pii:S0304-3835(21)00456-0 [Epub ahead of print].

Live-pathogenic bacteria, which were identified inside tumors hundreds year ago, are key elements in modern cancer research. As they have a relatively accessible genome, they offer a multitude of metabolic engineering opportunities, useful in several clinical fields. Better understanding of the tumor microenvironment and its associated microbiome would help conceptualize new metabolically engineered species, triggering efficient therapeutic responses against cancer. Unfortunately, given the low microbial biomass nature of tumors, characterizing the tumor microbiome remains a challenge. Tumors have a high host versus bacterial DNA ratio, making it extremely complex to identify tumor-associated bacteria. Nevertheless, with the improvements in next-generation analytic tools, recent studies demonstrated the existence of intratumor bacteria inside defined tumors. It is now proven that each cancer subtype has a unique microbiome, characterized by bacterial communities with specific metabolic functions. This review provides a brief overview of the main approaches used to characterize the tumor microbiome, and of the recently proposed functions of intracellular bacteria identified in oncological entities. The therapeutic aspects of live-pathogenic microbes are also discussed, regarding the tumor microenvironment of each cancer type.

RevDate: 2021-09-13

Takezawa K, Fujita K, Matsushita M, et al (2021)

The Firmicutes/Bacteroidetes ratio of the human gut microbiota is associated with prostate enlargement.

The Prostate [Epub ahead of print].

BACKGROUND: The pathophysiology of the prostate enlargement underlying lower urinary tract symptoms is unknown. Meanwhile, the gut microbiota can contribute to various host conditions. We hypothesized that the gut microbiota plays a role in prostate enlargement.

METHODS: We included 128 patients who underwent prostate biopsies at our hospitals between December 2018 and March 2020, excluding those who had used antibiotics within the past 6 months and those who were diagnosed with prostate cancer of cT3 or higher. Patients with prostate volumes ≥30 ml were defined as the prostate-enlargement (PE) group; those with prostate volumes <30 ml were defined as the non-PE group. Their gut microbiotas were analyzed via 16S rRNA metagenomic analyses of rectal swab samples and were compared between the groups.

RESULTS: The PE group included 66 patients; the non-PE group included 62 patients. Age, body mass index, and prostate-specific antigen levels did not significantly differ between the groups. Linear discriminant analysis effect size analysis indicated a higher proportion of Firmicutes and Actinobacteria in the PE group and a higher proportion of Bacteroidetes in the non-PE group. The Firmicutes/Bacteroidetes (F/B) ratio was significantly higher in the PE group than in the non-PE group (2.21 ± 0.39 vs. 1.61 ± 0.40, p = 0.015).

CONCLUSION: The F/B ratio of the gut microbiota was associated with prostate enlargement. Although the detailed mechanisms are unclear, the gut microbiota might affect prostate enlargement.

RevDate: 2021-09-13

Ma S, Ren B, Mallick H, et al (2021)

A statistical model for describing and simulating microbial community profiles.

PLoS computational biology, 17(9):e1008913 pii:PCOMPBIOL-D-21-00544 [Epub ahead of print].

Many methods have been developed for statistical analysis of microbial community profiles, but due to the complex nature of typical microbiome measurements (e.g. sparsity, zero-inflation, non-independence, and compositionality) and of the associated underlying biology, it is difficult to compare or evaluate such methods within a single systematic framework. To address this challenge, we developed SparseDOSSA (Sparse Data Observations for the Simulation of Synthetic Abundances): a statistical model of microbial ecological population structure, which can be used to parameterize real-world microbial community profiles and to simulate new, realistic profiles of known structure for methods evaluation. Specifically, SparseDOSSA's model captures marginal microbial feature abundances as a zero-inflated log-normal distribution, with additional model components for absolute cell counts and the sequence read generation process, microbe-microbe, and microbe-environment interactions. Together, these allow fully known covariance structure between synthetic features (i.e. "taxa") or between features and "phenotypes" to be simulated for method benchmarking. Here, we demonstrate SparseDOSSA's performance for 1) accurately modeling human-associated microbial population profiles; 2) generating synthetic communities with controlled population and ecological structures; 3) spiking-in true positive synthetic associations to benchmark analysis methods; and 4) recapitulating an end-to-end mouse microbiome feeding experiment. Together, these represent the most common analysis types in assessment of real microbial community environmental and epidemiological statistics, thus demonstrating SparseDOSSA's utility as a general-purpose aid for modeling communities and evaluating quantitative methods. An open-source implementation is available at

RevDate: 2021-09-13

Brandwein M, Fuks G, Israel A, et al (2021)

Biogeographical Landscape of the Human Face Skin Microbiome Viewed in High Definition.

Acta dermato-venereologica [Epub ahead of print].

The bacterial population that colonizes the human face imparts physiochemical and physiological effects on the facial skin. These skin-microbe interactions impact dermatological, cosmetic and skincare applications due to the centrality of the human face in daily interactions. However, fine-scale characterization of the human face skin microbiome is lacking. Using 16S rRNA sequencing and 3D cartography, this study plotted and characterized the facial skin microbiome in high-definition, based on 1,649 samples from 12 individuals. Analysis yielded a number of novel insights, including that of the relative uniformity of skin microbiome composition within skin sites, site localization of certain microbes, and the interpersonal variability of the skin microbiome. The results show that high-resolution topographical mapping of the skin microbiome is a powerful tool for studying the human skin microbiome. Despite a decade of skin microbiome research, there is still much to be discovered.

RevDate: 2021-09-13

Baur R, Gandhi J, Marshall NB, et al (2021)

Dermal exposure to the immunomodulatory antimicrobial chemical triclosan alters the skin barrier integrity and microbiome in mice.

Toxicological sciences : an official journal of the Society of Toxicology pii:6369529 [Epub ahead of print].

Triclosan is an antimicrobial chemical used in healthcare settings that can be absorbed through the skin. Exposure to triclosan has been positively associated with food and aeroallergy and asthma exacerbation in humans and, although not directly sensitizing, has been demonstrated to augment the allergic response in a mouse model of asthma. The skin barrier and microbiome are thought to play important roles in regulating inflammation and allergy and disruptions may contribute to development of allergic disease. To investigate potential connections of the skin barrier and microbiome with immune responses to triclosan, SKH1 mice were exposed dermally to triclosan (0.5-2%) or vehicle for up to 7 consecutive days. Exposure to 2% triclosan for 5-7 days on the skin was shown to increase trans-epidermal water loss levels. Seven days of dermal exposure to triclosan decreased filaggrin 2 and keratin 10 expression, but increased filaggrin and keratin 14 protein along with the danger signal S100a8 and interleukin-4. Dermal exposure to triclosan for 7 days also altered the alpha and beta diversity of the skin and gut microbiome. Specifically, dermal triclosan exposure increased the relative abundance of the Firmicutes family, Lachnospiraceae on the skin but decreased the abundance of Firmicutes family, Ruminococcaceae in the gut. Collectively, these results demonstrate that repeated dermal exposure to the antimicrobial chemical triclosan alters the skin barrier integrity and microbiome in mice, suggesting that these changes may contribute to the increase in allergic immune responses following dermal exposure to triclosan.

RevDate: 2021-09-13

Li C, Y Hu (2021)

Align resistant starch structures from plant-based foods with human gut microbiome for personalized health promotion.

Critical reviews in food science and nutrition [Epub ahead of print].

Resistant starch (RS) is beneficial for human health through its interactions with gut microbiota. However, the alignment between RS structures with gut microbiota profile and consequentially health benefits remain elusive. This review summarizes current understanding of RS complex structures and their interactions with the gut microbiota, aiming to highlight the possibility of manipulating RS structures for a targeted and predictable gut microbiota shift for human health in a personalized way. Current definition of RS types is strongly associated with starch digestion behaviors in small intestine, which does not precisely reflect their interactions with human gut microbiota. Distinct alterations of gut microbiota could be associated with the same RS type. The principles to describe the specificity of different RS structural characteristics in terms of aligning with human gut microbiota shift was proposed in this review, which could result in new definitions of RS types from the microbial perspectives. To consider the highly variable personal features, a machine-learning algorithm to integrate different personalized factors and better understand the complex interaction between RS and gut microbiota and its effects on individual health was explained. This review contains important information to bring interactions between RS and gut microbiota to translational practice.

RevDate: 2021-09-13

Scott DA, Dukka H, D Saxena (2021)

Potential Mechanisms Underlying Marijuana-Associated Periodontal Tissue Destruction.

Journal of dental research [Epub ahead of print].

While definitive evidence awaits, cannabis is emerging as a likely risk factor for periodontal tissue destruction. The mechanisms that underlie potential cannabis-induced or cannabis-enhanced periodontal diseases, however, remain to be elucidated. Herein, we 1) examine insights obtained from the endocannabinoid system, 2) summarize animal models of exposure to cannabinoid receptor agonists and antagonists, 3) review the evidence suggesting that cannabis and cannabis-derived molecules exert a profound influence on components of the oral microbiome, and 4) assess studies indicating that marijuana and phytocannabinoids compromise the immune response to plaque. Furthermore, we address how knowledge of cannabinoid influences in the oral cavity may be exploited to provide potential novel periodontal therapeutics, while recognizing that such medicinal approaches may be most appropriate for nonhabitual marijuana users. The suspected increase in susceptibility to periodontitis in marijuana users is multifaceted, and it is clear that we are only beginning to understand the complex toxicological, cellular, and microbial interactions involved. With marijuana consumption increasing across all societal demographics, periodontal complications of use may represent a significant, growing oral health concern. In preparation, an enhanced research response would seem appropriate.

RevDate: 2021-09-13

McGuire MK, MA McGuire (2021)

Microbiomes and Childhood Malnutrition: What Is the Evidence?.

Annals of nutrition & metabolism pii:000519001 [Epub ahead of print].

Both undernutrition and overnutrition continue to represent enduring global health crises, and with the growing implications of both forms of malnutrition occurring simultaneously in individuals and populations (referred to as the double burden of malnutrition), understanding their biological and environmental causes is a primary research and humanitarian necessity. There is growing evidence of a bidirectional association between variation in the gastrointestinal (GI) microbiome and risk of/resilience to malnutrition during early life. For example, studies of siblings who discordantly do or do not develop severe malnutrition show clear differences in the diversity and composition of fecal microbiomes. These differences are transiently lessened during refeeding but re-emerge thereafter. These findings have been somewhat recapitulated using animal models, but small sample sizes and limited range complicate interpretation of results and applicability to humans. Mechanisms driving these differences are currently unknown but likely involve a combination of inflammatory pathways (and perhaps antioxidant status of the host) and effects on nutrient availability, requirements, and utilization by both host and microbe. A less robust literature also suggests that variation in GI microbiome is associated with risk for obesity during childhood. The putative impact of GI microbiomes on malnutrition is likely modified by a variety of important variables such as genetics (likely driven, in part, by evolution), environmental pathogen exposure and its timing, dietary factors, and cultural/societal pattern (e.g., use of antibiotics). Given the growing double burden of malnutrition, this topic demands a focused interdisciplinary approach that expands from merely characterizing differences and longitudinal changes in fecal microbes to examining their functionality during early life. Understanding the complex composition of human milk and how its components impact establishment and maintenance of the recipient infant's GI microbiome will also undoubtedly shed important light on this topic.

RevDate: 2021-09-13

Marongiu L, H Allgayer (2021)

Viruses in colorectal cancer.

Molecular oncology [Epub ahead of print].

Increasing evidence suggests that microorganisms might represent at least highly interesting co-factors in colorectal cancer (CRC) oncogenesis and progression. Still, associated mechanisms, specifically in colonocytes and their microenvironmental interactions, are still poorly understood. Although, currently, at least seven viruses are being recognized as human carcinogens, only three of these - Epstein-Barr virus (EBV), human papillomavirus (HPV) and John Cunningham virus (JCV) - have been described, with varying levels of evidence, in CRC. In addition, cytomegalovirus (CMV) has been associated with CRC in some publications, albeit not being a fully acknowledged oncovirus. Moreover, recent microbiome studies set increasing grounds for new hypotheses on bacteriophages as interesting additional modulators in CRC carcinogenesis and progression. The present Review summarizes how particular groups of viruses, including bacteriophages, affect cells and the cellular and microbial microenvironment, thereby putatively contributing to foster CRC. This could be achieved, for example, by promoting several processes - such as DNA damage, chromosomal instability, or molecular aspects of cell proliferation, CRC progression and metastasis - not necessarily by direct infection of epithelial cells only, but also via interaction with the microenvironment of infected cells. In this context, there are striking common features of EBV, CMV, HPV and JCV that are able to promote oncogenesis, in terms of establishing latent infections and affecting p53-/pRb-driven, epithelial-mesenchymal transition (EMT)-/EGFR-associated, and especially Wnt/β-catenin-driven pathways. We speculate that, at least in part, such viral impacts on particular pathways might be reflected in lasting (e.g., mutational or further genomic) fingerprints of viruses in cells. Also, the complex interplay between several species within the intestinal microbiome, involving a direct impact on colorectal and microenvironmental cells but also between, for example, phages and bacterial and viral pathogens, certainly might, in part, explain ongoing difficulties to establish unequivocal monocausal links between specific viral infections and CRC.

RevDate: 2021-09-13

Suchodolski JS (2021)

Analysis of the gut microbiome in dogs and cats.

Veterinary clinical pathology [Epub ahead of print].

The gut microbiome is an important immune and metabolic organ. Intestinal bacteria produce various metabolites that influence the health of the intestine and other organ systems, including kidney, brain, and heart. Changes in the microbiome in diseased states are termed dysbiosis. The concept of dysbiosis is constantly evolving and includes changes in microbiome diversity and/or structure and functional changes (eg, altered production of bacterial metabolites). Molecular tools are now the standard for microbiome analysis. Sequencing of microbial genes provides information about the bacteria present and their functional potential but lacks standardization and analytical validation of methods and consistency in the reporting of results. This makes it difficult to compare results across studies or for individual clinical patients. The Dysbiosis Index (DI) is a validated quantitative PCR assay for canine fecal samples that measures the abundance of seven important bacterial taxa and summarizes the results as one single number. Reference intervals are established for dogs, and the DI can be used to assess the microbiome in clinical patients over time and in response to therapy (eg, fecal microbiota transplantation). In situ hybridization or immunohistochemistry allows the identification of mucosa-adherent and intracellular bacteria in animals with intestinal disease, especially granulomatous colitis. Future directions include the measurement of bacterial metabolites in feces or serum as markers for the appropriate function of the microbiome. This article summarizes different approaches to the analysis of gut microbiota and how they might be applicable to research studies and clinical practice in dogs and cats.

RevDate: 2021-09-13

Sarbagili Shabat C, Scaldaferri F, Zittan E, et al (2021)

Use of Fecal transplantation with a novel diet for mild to moderate active ulcerative colitis: The CRAFT UC randomized controlled trial.

Journal of Crohn's & colitis pii:6369227 [Epub ahead of print].

BACKGROUND: We evaluated whether integration of novel diets for donors and patients in addition to fecal transplantation (FT) could increase FT remission rate in refractory ulcerative colitis (UC).

METHODS: This was a blinded randomized controlled trial in adults with active UC, defined by a simple clinical colitis activity index (SCCAI) of ≥5 and ≤ 11 and endoscopic Mayo score 2-3, refractory to medication. Group 1 received free diet and single donor standard FT by colonoscopy on day 1and rectal enemas on days 2 and 14 without dietary conditioning of the donor. Group 2: FT as above but with dietary pre-conditioning of the donor for 14 days and a UC Exclusion Diet (UCED) for the patients. Group 3 received the UCED alone. The primary endpoint was week 8 clinical steroid free remission, defined as SCCAI <3.

RESULTS: Sixty two of 96 planned patients were enrolled. Remission week 8 Group 1 was 2/17 (11.8%), Group 2 4/19 (21.1%), Group 3 6/15 (40%) (NS). Endoscopic remission was Group 1 2/17 (12%), Group 2 3/19 (16%), Group 3 4/15 (27%) (Group 1 vs.3 p=0.38). Mucosal healing (Mayo 0) was achieved only in Group 3 (3/15, 20%) vs. 0/36 FT patients (p=0.022). Exacerbation of disease occurred in 3/17 (17.6%) Group 1, 4/19 (21.1%) Group 2, and 1/15 (6.7%) Group 3 (Group 2 vs.3, p=0.35).

CONCLUSIONS: UCED alone appeared to achieve higher clinical remission and mucosal healing than single donor FT with or without diet. The study was stopped for futility by a safety monitoring board.

RevDate: 2021-09-13

Nogal B, Blumberg JB, Blander G, et al (2021)

Gut Microbiota-Informed Precision Nutrition in the Generally Healthy Individual: Are We There Yet?.

Current developments in nutrition, 5(9):nzab107 pii:nzab107.

Since next generation sequencing facilitated high-throughput and cost-efficient genomics analyses, the human gut metagenome has become an emerging frontier to explore toward precision nutrition. Significant progress has been made in identifying gut microbial features associated with a wide spectrum of human disease. However, other than a few microbiome-disease relations, there is a dearth of confirmed causal inferences, particularly in generally healthy populations. The relatively high unexplained variability in microbiome compositions in this group warrants caution in applying this complex biomarker toward precision nutrition, because our understanding of what constitutes a healthy microbiome is still rudimentary. Although gut microbiota harbor integrated environmental and host-specific information with the potential to facilitate personalized nutritional and lifestyle advice, these data cannot yet be confidently interpreted toward precise recommendations. Thus, nutritional advice for generally healthy individuals based on personal microbiome composition analysis might not yet be appropriate unless accompanied by established blood and physiological biomarkers.

RevDate: 2021-09-13

Pandey K, S Umar (2021)

Microbiome in drug resistance to colon cancer.

Current opinion in physiology, 23:.

Metagenomic analyses have revealed microbial dysbiosis in the gut of patients with colorectal cancer (CRC). The gut microbiota influences CRC via a variety of mechanisms, including microbial-derived factors such as metabolites or genotoxins. Pathogenic drivers and opportunistic passenger bacteria may underlie direct effect of the gut microbiota on carcinogenesis. We posit that metabolites generated by gut microbiota can influence CRC through a multitude of epigenetic or genetic effects on malignant transformation. A closer look at the cross talks between the commensals, epithelial cells, immune regulators etc., needs to be established with more substantiated studies. The recurrence of chemoresistant disease following therapy undoubtedly provides the impetus for morbidity and mortality; yet, the role of gut microbiome in drug resistance remains to be fully investigated. We review the current literature on microbial dysbiosis during CRC and discuss the mechanistic basis of CRC-associated bacteria in tumor initiation, progression and drug resistance.

RevDate: 2021-09-13

Jergens AE, Parvinroo S, Kopper J, et al (2021)

Rules of Engagement: Epithelial-Microbe Interactions and Inflammatory Bowel Disease.

Frontiers in medicine, 8:669913.

Inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), are complex, multifactorial disorders that lead to chronic and relapsing intestinal inflammation. The exact etiology remains unknown, however multiple factors including the environment, genetic, dietary, mucosal immunity, and altered microbiome structure and function play important roles in disease onset and progression. Supporting this notion that the gut microbiota plays a pivotal role in IBD pathogenesis, studies in gnotobiotic mice have shown that mouse models of intestinal inflammation require a microbial community to develop colitis. Additionally, antimicrobial therapy in some IBD patients will temporarily induce remission further demonstrating an association between gut microbes and intestinal inflammation. Finally, a dysfunctional intestinal epithelial barrier is also recognized as a key pathogenic factor in IBD. The intestinal epithelium serves as a barrier between the luminal environment and the mucosal immune system and guards against harmful molecules and microorganisms while being permeable to essential nutrients and solutes. Beneficial (i.e., mutualists) bacteria promote mucosal health by strengthening barrier integrity, increasing local defenses (mucin and IgA production) and inhibiting pro-inflammatory immune responses and apoptosis to promote mucosal homeostasis. In contrast, pathogenic bacteria and pathobionts suppress expression and localization of tight junction proteins, cause dysregulation of apoptosis/proliferation and increase pro-inflammatory signaling that directly damages the intestinal mucosa. This review article will focus on the role of intestinal epithelial cells (IECs) and the luminal environment acting as mediators of barrier function in IBD. We will also share some of our translational observations of interactions between IECs, immune cells, and environmental factors contributing to maintenance of mucosal homeostasis, as it relates to GI inflammation and IBD in different animal models.

RevDate: 2021-09-13

Lang JM, Sedgeman LR, Cai L, et al (2021)

Dietary and Pharmacologic Manipulations of Host Lipids and Their Interaction With the Gut Microbiome in Non-human Primates.

Frontiers in medicine, 8:646710.

The gut microbiome influences nutrient processing as well as host physiology. Plasma lipid levels have been associated with the microbiome, although the underlying mechanisms are largely unknown, and the effects of dietary lipids on the gut microbiome in humans are not well-studied. We used a compilation of four studies utilizing non-human primates (Chlorocebus aethiops and Macaca fascicularis) with treatments that manipulated plasma lipid levels using dietary and pharmacological techniques, and characterized the microbiome using 16S rDNA. High-fat diets significantly reduced alpha diversity (Shannon) and the Firmicutes/Bacteroidetes ratio compared to chow diets, even when the diets had different compositions and were applied in different orders. When analyzed for differential abundance using DESeq2, Bulleidia, Clostridium, Ruminococcus, Eubacterium, Coprocacillus, Lachnospira, Blautia, Coprococcus, and Oscillospira were greater in both chow diets while Succinivibrio, Collinsella, Streptococcus, and Lactococcus were greater in both high-fat diets (oleic blend or lard fat source). Dietary cholesterol levels did not affect the microbiome and neither did alterations of plasma lipid levels through treatments of miR-33 antisense oligonucleotide (anti-miR-33), Niemann-Pick C1-Like 1 (NPC1L1) antisense oligonucleotide (ASO), and inducible degrader of LDLR (IDOL) ASO. However, a liver X receptor (LXR) agonist shifted the microbiome and decreased bile acid levels. Fifteen genera increased with the LXR agonist, while seven genera decreased. Pseudomonas increased on the LXR agonist and was negatively correlated to deoxycholic acid, cholic acid, and total bile acids while Ruminococcus was positively correlated with taurolithocholic acid and taurodeoxycholic acid. Seven of the nine bile acids identified in the feces significantly decreased due to the LXR agonist, and total bile acids (nmol/g) was reduced by 62%. These results indicate that plasma lipid levels have, at most, a modest effect on the microbiome, whereas bile acids, derived in part from plasma lipids, are likely responsible for the indirect relationship between lipid levels and the microbiome.

RevDate: 2021-09-13

Graf AC, Striesow J, Pané-Farré J, et al (2021)

An Innovative Protocol for Metaproteomic Analyses of Microbial Pathogens in Cystic Fibrosis Sputum.

Frontiers in cellular and infection microbiology, 11:724569.

Hallmarks of cystic fibrosis (CF) are increased viscosity of mucus and impaired mucociliary clearance within the airways due to mutations of the cystic fibrosis conductance regulator gene. This facilitates the colonization of the lung by microbial pathogens and the concomitant establishment of chronic infections leading to tissue damage, reduced lung function, and decreased life expectancy. Although the interplay between key CF pathogens plays a major role during disease progression, the pathophysiology of the microbial community in CF lungs remains poorly understood. Particular challenges in the analysis of the microbial population present in CF sputum is (I) the inhomogeneous, viscous, and slimy consistence of CF sputum, and (II) the high number of human proteins masking comparably low abundant microbial proteins. To address these challenges, we used 21 CF sputum samples to develop a reliable, reproducible and widely applicable protocol for sputum processing, microbial enrichment, cell disruption, protein extraction and subsequent metaproteomic analyses. As a proof of concept, we selected three sputum samples for detailed metaproteome analyses and complemented and validated metaproteome data by 16S sequencing, metabolomic as well as microscopic analyses. Applying our protocol, the number of bacterial proteins/protein groups increased from 199-425 to 392-868 in enriched samples compared to nonenriched controls. These early microbial metaproteome data suggest that the arginine deiminase pathway and multiple proteases and peptidases identified from various bacterial genera could so far be underappreciated in their contribution to the CF pathophysiology. By providing a standardized and effective protocol for sputum processing and microbial enrichment, our study represents an important basis for future studies investigating the physiology of microbial pathogens in CF in vivo - an important prerequisite for the development of novel antimicrobial therapies to combat chronic recurrent airway infection in CF.

RevDate: 2021-09-13

Lettieri GM, Santiago LM, Lettieri GC, et al (2021)

Oral Phenotype and Salivary Microbiome of Individuals With Papillon-Lefèvre Syndrome.

Frontiers in cellular and infection microbiology, 11:720790.

Papillon-Lefèvre syndrome (PLS) is an autosomal recessive rare disease, main characteristics of which include palmoplantar hyperkeratosis and premature edentulism due to advanced periodontitis (formerly aggressive periodontitis). This study aimed to characterize the oral phenotype, including salivary parameters, and the salivary microbiome of three PLS sisters, comparatively. Two sisters were toothless (PLSTL1 and PLSTL2), and one sister had most of the teeth in the oral cavity (PLST). Total DNA was extracted from the unstimulated saliva, and the amplicon sequencing of the 16S rRNA gene fragment was performed in an Ion PGM platform. The amplicon sequence variants (ASVs) were obtained using the DADA2 pipeline, and the taxonomy was assigned using the SILVA v.138. The main phenotypic characteristics of PLS were bone loss and premature loss of primary and permanent dentition. The PLST sister presented advanced periodontitis with gingival bleeding and suppuration, corresponding to the advanced periodontitis as a manifestation of systemic disease, stage IV, grade C. All three PLS sisters presented hyposalivation as a possible secondary outcome of the syndrome. Interestingly, PLST salivary microbiota was dominated by the uncultured bacteria Bacterioidales (F0058), Fusobacterium, Treponema, and Sulfophobococcus (Archaea domain). Streptococcus, Haemophilus, and Caldivirga (Archaea) dominated the microbiome of the PLSTL1 sister, while the PLSTL2 had higher abundances of Lactobacillus and Porphyromonas. This study was the first to show a high abundance of organisms belonging to the Archaea domain comprising a core microbiome in human saliva. In conclusion, a PLST individual does have a microbiota different from that of the periodontitis' aggressiveness previously recognized. Due to an ineffective cathepsin C, the impairment of neutrophils probably provided a favorable environment for the PLS microbiome. The interactions of Bacteroidales F0058, Caldivirga, and Sulfophobococcus with the microbial consortium of PLS deserves future investigation. Traditional periodontal therapy is not efficient in PLS patients. Unraveling the PLS microbiome is essential in searching for appropriate treatment and avoiding early tooth loss.

RevDate: 2021-09-13

Liu X, Pan X, Liu H, et al (2021)

Gut Microbial Diversity in Female Patients With Invasive Mole and Choriocarcinoma and Its Differences Versus Healthy Controls.

Frontiers in cellular and infection microbiology, 11:704100.

Objective: To investigate variation in gut microbiome in female patients with invasive mole (IM) and choriocarcinoma (CC) and compare it with healthy controls.

Methods: Fecal microbiome of 12 female patients with IM, 9 female patients with CC, and 24 healthy females were analyzed based on 16s rDNA sequencing. Alpha (α) diversity was evaluated using Shannon diversity index and Pielou evenness index, while beta (β) diversity was assessed using principle coordinate analysis (PCoA) of unweighted Unifrac distances. The potential functional changes of microbiomes were predicted using Tax4Fun. The relative abundance of microbial taxa was compared using Welch's t test. The role of varied gut microbiota was analyzed via receiver operating characteristic (ROC) curve.

Results: The α diversity and β diversity were significantly different between IM patients and controls, but not between CC patients and controls. In addition, the abundance of cancer-related genes was significantly increased in IM and CC patients. Notably, a total of 19 families and 39 genera were found to have significant differences in bacterial abundance. ROC analysis indicated that Prevotella_7 may be a potential biomarker among IM, CC, and controls.

Conclusion: Our study demonstrated that the diversity and composition of gut microbiota among IM patients, CC patients, and healthy females were significantly different, which provides rationale for using gut microbiota as diagnostic markers and treatment targets, as well as for further study of gut microbiota in gestational trophoblastic neoplasia (GTN).

RevDate: 2021-09-13

Innes AJ, Mullish BH, Ghani R, et al (2021)

Fecal Microbiota Transplant Mitigates Adverse Outcomes Seen in Patients Colonized With Multidrug-Resistant Organisms Undergoing Allogeneic Hematopoietic Cell Transplantation.

Frontiers in cellular and infection microbiology, 11:684659.

The gut microbiome can be adversely affected by chemotherapy and antibiotics prior to hematopoietic cell transplantation (HCT). This affects graft success and increases susceptibility to multidrug-resistant organism (MDRO) colonization and infection. We performed an initial retrospective analysis of our use of fecal microbiota transplantation (FMT) from healthy donors as therapy for MDRO-colonized patients with hematological malignancy. FMT was performed on eight MDRO-colonized patients pre-HCT (FMT-MDRO group), and outcomes compared with 11 MDRO colonized HCT patients from the same period. At 12 months, survival was significantly higher in the FMT-MDRO group (70% versus 36% p = 0.044). Post-HCT, fewer FMT-MDRO patients required intensive care (0% versus 46%, P = 0.045) or experienced fever (0.29 versus 0.11 days, P = 0.027). Intestinal MDRO decolonization occurred in 25% of FMT-MDRO patients versus 11% non-FMT MDRO patients. Despite the significant differences and statistically comparable patient/transplant characteristics, as the sample size was small, a matched-pair analysis between both groups to non-MDRO colonized control cohorts (2:1 matching) was performed. At 12 months, the MDRO group who did not have an FMT had significantly lower survival (36.4% versus 61.9% respectively, p=0.012), and higher non relapse mortality (NRM; 60.2% versus 16.7% respectively, p=0.009) than their paired non-MDRO-colonized cohort. Conversely, there was no difference in survival (70% versus 43.4%, p=0.14) or NRM (12.5% versus 31.2% respectively, p=0.24) between the FMT-MDRO group and their paired non-MDRO cohort. Collectively, these data suggest that negative clinical outcomes, including mortality associated with MDRO colonization, may be ameliorated by pre-HCT FMT, even in the absence of intestinal MDRO decolonization. Further work is needed to explore this observed benefit.

RevDate: 2021-09-13

Ruo SW, Alkayyali T, Win M, et al (2021)

Role of Gut Microbiota Dysbiosis in Breast Cancer and Novel Approaches in Prevention, Diagnosis, and Treatment.

Cureus, 13(8):e17472.

Breast cancer is the most common cause of cancer-related deaths in women. Breast cancer is still a major cause of morbidity and mortality among women despite all the available diagnostic and treatment modalities. The gut microbiota has drawn keen interest as an additional environmental risk factor in breast cancer, especially in sporadic cases. This article explores factors that disrupt the normal gut microbial composition and the role of gut microbial dysbiosis in the development of breast cancer. We finalized 40 relevant articles after searching Pubmed and Google Scholar using regular keywords and the Medical Subject Headings (MeSH) strategy. Gut microbiota dysbiosis has been shown to play a role in the development of breast cancer via estrogen-dependent mechanisms and non-estrogen-dependent mechanisms involving the production of microbial-derived metabolites, immune regulation, and effects on DNA. The gut microbiota influence estrogen metabolism hence estrogen levels. The metabolites that have demonstrated anticancer properties include lithocholic acid, butyrate, and cadaverine. New approaches targeting the gut microbiota have come up and may yield new advances in the prevention, diagnosis, and treatment of breast cancer. They include the use of prebiotics, probiotics, and hormone supplements to restore normobiosis in the prevention and treatment of breast cancer.

RevDate: 2021-09-13

Da Silva K, Pons N, Berland M, et al (2021)

StrainFLAIR: strain-level profiling of metagenomic samples using variation graphs.

PeerJ, 9:e11884 pii:11884.

Current studies are shifting from the use of single linear references to representation of multiple genomes organised in pangenome graphs or variation graphs. Meanwhile, in metagenomic samples, resolving strain-level abundances is a major step in microbiome studies, as associations between strain variants and phenotype are of great interest for diagnostic and therapeutic purposes. We developed StrainFLAIR with the aim of showing the feasibility of using variation graphs for indexing highly similar genomic sequences up to the strain level, and for characterizing a set of unknown sequenced genomes by querying this graph. On simulated data composed of mixtures of strains from the same bacterial species Escherichia coli, results show that StrainFLAIR was able to distinguish and estimate the abundances of close strains, as well as to highlight the presence of a new strain close to a referenced one and to estimate its abundance. On a real dataset composed of a mix of several bacterial species and several strains for the same species, results show that in a more complex configuration StrainFLAIR correctly estimates the abundance of each strain. Hence, results demonstrated how graph representation of multiple close genomes can be used as a reference to characterize a sample at the strain level.

RevDate: 2021-09-13

Panahabadi R, Ahmadikhah A, McKee LS, et al (2021)

Genome-Wide Association Mapping of Mixed Linkage (1,3;1,4)-β-Glucan and Starch Contents in Rice Whole Grain.

Frontiers in plant science, 12:665745.

The glucan content of rice is a key factor defining its nutritional and economic value. Starch and its derivatives have many industrial applications such as in fuel and material production. Non-starch glucans such as (1,3;1,4)-β-D-glucan (mixed-linkage β-glucan, MLG) have many benefits in human health, including lowering cholesterol, boosting the immune system, and modulating the gut microbiome. In this study, the genetic variability of MLG and starch contents were analyzed in rice (Oryza sativa L.) whole grain, by performing a new quantitative analysis of the polysaccharide content of rice grains. The 197 rice accessions investigated had an average MLG content of 252 μg/mg, which was negatively correlated with the grain starch content. A new genome-wide association study revealed seven significant quantitative trait loci (QTLs) associated with the MLG content and two QTLs associated with the starch content in rice whole grain. Novel genes associated with the MLG content were a hexose transporter and anthocyanidin 5,3-O-glucosyltransferase. Also, the novel gene associated with the starch content was a nodulin-like domain. The data pave the way for a better understanding of the genes involved in determining both MLG and starch contents in rice grains and should facilitate future plant breeding programs.

RevDate: 2021-09-13

Bozward AG, Ronca V, Osei-Bordom D, et al (2021)

Gut-Liver Immune Traffic: Deciphering Immune-Pathogenesis to Underpin Translational Therapy.

Frontiers in immunology, 12:711217.

The tight relationship between the gut and liver on embryological, anatomical and physiological levels inspired the concept of a gut-liver axis as a central element in the pathogenesis of gut-liver axis diseases. This axis refers to the reciprocal regulation between these two organs causing an integrated system of immune homeostasis or tolerance breakdown guided by the microbiota, the diet, genetic background, and environmental factors. Continuous exposure of gut microbiome, various hormones, drugs and toxins, or metabolites from the diet through the portal vein adapt the liver to maintain its tolerogenic state. This is orchestrated by the combined effort of immune cells network: behaving as a sinusoidal and biliary firewall, along with a regulatory network of immune cells including, regulatory T cells and tolerogenic dendritic cells (DC). In addition, downregulation of costimulatory molecules on hepatic sinusoids, hepatocytes and biliary epithelial cells as well as regulating the bile acids chain also play a part in hepatic immune homeostasis. Recent evidence also demonstrated the link between changes in the gut microbiome and liver resident immune cells in the progression of cirrhosis and the tight correlation among primary sclerosing cholangitis (PSC) and also checkpoint induced liver and gut injury. In this review, we will summarize the most recent evidence of the bidirectional relationship among the gut and the liver and how it contributes to liver disease, focusing mainly on PSC and checkpoint induced hepatitis and colitis. We will also focus on completed therapeutic options and on potential targets for future treatment linking with immunology and describe the future direction of this research, taking advantage of modern technologies.

RevDate: 2021-09-13

Fujiwara H (2021)

Crosstalk Between Intestinal Microbiota Derived Metabolites and Tissues in Allogeneic Hematopoietic Cell Transplantation.

Frontiers in immunology, 12:703298.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an evidence based- cellular immunotherapy for hematological malignancies. Immune reactions not only promote graft-versus-tumor effects that kill hematological malignant cells but also graft-versus-host disease (GVHD) that is the primary complication characterized by systemic organ damages consisting of T-cells and antigen presenting cells (APCs) activation. GVHD has long been recognized as an immunological reaction that requires an immunosuppressive treatment targeting immune cells. However immune suppression cannot always prevent GVHD or effectively treat it once it has developed. Recent studies using high-throughput sequencing technology investigated the impact of microbial flora on GVHD and provided profound insights of the mechanism of GVHD other than immune cells. Allo-HSCT affects the intestinal microbiota and microbiome-metabolome axis that can alter intestinal homeostasis and the severity of experimental GVHD. This axis can potentially be manipulated via dietary intervention or metabolites produced by intestinal bacteria affected post-allo-HSCT. In this review, we discuss the mechanism of experimental GVHD regulation by the complex microbial community-metabolites-host tissue axis. Furthermore, we summarize the major findings of microbiome-based immunotherapeutic approaches that protect tissues from experimental GVHD. Understanding the complex relationships between gut microbiota-metabolites-host tissues axis provides crucial insight into the pathogenesis of GVHD and advances the development of new therapeutic approaches.

RevDate: 2021-09-13

Benner M, Lopez-Rincon A, Thijssen S, et al (2021)

Antibiotic Intervention Affects Maternal Immunity During Gestation in Mice.

Frontiers in immunology, 12:685742.

Background: Pregnancy is a portentous stage in life, during which countless events are precisely orchestrated to ensure a healthy offspring. Maternal microbial communities are thought to have a profound impact on development. Although antibiotic drugs may interfere in these processes, they constitute the most frequently prescribed medication during pregnancy to prohibit detrimental consequences of infections. Gestational antibiotic intervention is linked to preeclampsia and negative effects on neonatal immunity. Even though perturbations in the immune system of the mother can affect reproductive health, the impact of microbial manipulation on maternal immunity is still unknown.

Aim: To assess whether antibiotic treatment influences maternal immunity during pregnancy.

Methods: Pregnant mice were treated with broad-spectrum antibiotics. The maternal gut microbiome was assessed. Numerous immune parameters throughout the maternal body, including placenta and amniotic fluid were investigated and a novel machine-learning ensemble strategy was used to identify immunological parameters that allow distinction between the control and antibiotic-treated group.

Results: Antibiotic treatment reduced diversity of maternal microbiota, but litter sizes remained unaffected. Effects of antibiotic treatment on immunity reached as far as the placenta. Four immunological features were identified by recursive feature selection to contribute to the most robust classification (splenic T helper 17 cells and CD5+ B cells, CD4+ T cells in mesenteric lymph nodes and RORγT mRNA expression in placenta).

Conclusion: In the present study, antibiotic treatment was able to affect the carefully coordinated immunity during pregnancy. These findings highlight the importance of inclusion of immunological parameters when studying the effects of medication used during gestation.

RevDate: 2021-09-13

Fortmann I, Dammann MT, Siller B, et al (2021)

Infants Younger Than 90 Days Admitted for Late-Onset Sepsis Display a Reduced Abundance of Regulatory T Cells.

Frontiers in immunology, 12:666447.

Objective: To provide epidemiological data of infants < 90 days of age with suspected late-onset sepsis (LOS) and evaluate distinct immunological specificities. We hypothesized that previously healthy infants < 3 months of age with sepsis have a yet undefined immunological predisposition; e.g. differences in lymphocyte subsets including regulatory T cells.

Methods: We performed an exploratory, single center study between January 1st, 2019 and June 1st, 2021. Routine diagnostics included conventional culture (blood, cerebrospinal fluid, urine), PCR and inflammatory markers in infants < 90 days of age with suspected sepsis. We additionally analyzed lymphocyte subsets and CD4+ CD25+ forkhead box protein (FoxP3)+ Tregs at admission for sepsis workup as compared to age-matched controls.

Results: A convenience sample cohort of n= 51 infants with sepsis workup was enrolled. Invasive bacterial infection (IBI) was diagnosed in 25 (49.0%) patients including two infants with a rhinovirus co-infection and viral infection in 14 (27.5%) neonates. No infectious cause was found in 12 cases. Infants with suspected LOS displayed a decreased abundance of CD4+ FoxP3+ T cells as compared to controls, which was most pronounced in the subgroup of infants with IBI. We also noticed elevated HLA-DR-positive CD3+ cells in infants with LOS and a higher CD4/CD8-ratio in infants with viral infection as compared to healthy controls. Infants with viral infections had a higher number of natural killer cells as compared to infants with IBI.

Conclusion: Our exploratory data support the concept of a potential immaturity state and failed immune tolerance development for young infants with LOS. Future large-scale studies are needed to elucidate pre-sepsis conditions and to target the microbiome-immunity interplay as a potential risk pattern.

RevDate: 2021-09-13

Li Y, Cai Y, Huang Q, et al (2021)

Altered Fecal Microbiome and Metabolome in a Mouse Model of Choroidal Neovascularization.

Frontiers in microbiology, 12:738796.

Purpose: Choroidal neovascularization (CNV) is the defining feature of neovascular age-related macular degeneration (nAMD). Gut microbiota might be deeply involved in the pathogenesis of nAMD. This study aimed to reveal the roles of the gut microbiome and fecal metabolome in a mouse model of laser-induced CNV.

Methods: The feces of C57BL/6J mice with or without laser-induced CNV were collected. Multi-omics analyses, including 16S rRNA gene sequencing and untargeted metabolomics, were conducted to analyze the changes in the gut microbial composition and the fecal metabolomic profiles in CNV mice.

Results: The gut microbiota was significantly altered in CNV mice. The abundance of Candidatus_Saccharimonas was significantly upregulated in the feces of CNV mice, while 16 genera, including Prevotellaceae_NK3B31_group, Candidatus_Soleaferrea, and Truepera, were significantly more abundant in the controls than in the CNV group. Fecal metabolomics identified 73 altered metabolites (including 52 strongly significantly altered metabolites) in CNV mice compared to control mice. Correlation analysis indicated significant correlations between the altered fecal metabolites and gut microbiota genera, such as Lachnospiraceae_UCG-001 and Candidatus_Saccharimonas. Moreover, KEGG analysis revealed six pathways associated with these altered metabolites, such as the ABC transporter, primary bile acid biosynthesis and steroid hormone biosynthesis pathways.

Conclusion: The study identified an altered fecal microbiome and metabolome in a CNV mouse model. The altered microbes, metabolites and the involved pathways might be associated with the pathogenesis of nAMD.

RevDate: 2021-09-13

Zhang Y, Gao C, Masum MMI, et al (2021)

Dynamic Microbiome Changes Reveal the Effect of 1-Methylcyclopropene Treatment on Reducing Post-harvest Fruit Decay in "Doyenne du Comice" Pear.

Frontiers in microbiology, 12:729014.

Pathogen-induced decay is one of the most common causes of fruit loss, resulting in substantial economic loss and posing a health risk to humans. As an ethylene action inhibitor, 1-methylcyclopropene (1-MCP) can significantly reduce fruit decay, but its effect on fruit pathogens remains unclear. Herein, the change in microbial community structure was analyzed using the high-throughput sequencing technology, and characteristics related to fruit quality were determined after 1-MCP (1.0 M l L-1) treatment in "Doyenne du Comiceis" pear fruit during storage at ambient temperature. Overall, 1-MCP was highly effective in reducing disease incidence and induced multiple changes of the fungal and bacterial microbiota. At day 15, the microbial diversity of fungi or bacteria was reduced significantly in the control fruit (non-treated with 1-MCP), which had the most severe decay incidence. For fungi, in addition to Alternaria being the most abundant in both 1-MCP treatment (59.89%) and control (40.18%), the abundances of Botryosphaeria (16.75%), Penicillium (8.81%), and Fusarium (6.47%) increased significantly with the extension of storage time. They became the primary pathogens to cause fruit decay in control, but they were markedly decreased in 1-MCP treatment, resulting in reduced disease incidence. For bacteria, the abundance of Gluconobacter (50.89%) increased dramatically at day 15 in the control fruit, showing that it also played a crucial role in fruit decay. In addition, Botryosphaeria, Fusarium fungi, and Massilia, Kineococcus bacteria were identified as biomarkers to distinguish 1-MCP treatment and control using Random Forest analysis. The redundancy analysis (RDA) result showed that the amount of Botryosphaeria, Penicillium, and Fusarium were positively correlated with disease incidence and respiration rate of pear fruits while negatively correlated with fruit firmness. This investigation is the first comprehensive analysis of the microbiome response to 1-MCP treatment in post-harvest pear fruit, and reveals the relationship between fruit decay and microbial composition in pear fruit.

RevDate: 2021-09-13

Zhang R, Zhong Z, Ma H, et al (2021)

Mucosal Microbiota and Metabolome in the Ileum of Hu Sheep Offered a Low-Grain, Pelleted or Non-pelleted High-Grain Diet.

Frontiers in microbiology, 12:718884.

Alterations in mucosal microbiota and metabolites are critical to intestinal homeostasis and host health. This study used a combination of 16S rRNA gene sequencing and liquid chromatography-mass spectrometry (LC/MS) to investigate mucosal microbiota and their metabolic profiles in the ileum of Hu sheep fed different diets. Here, we randomly allocated 15 Hu sheep to three diets, a non-pelleted low-grain diet (control diet; CON), a non-pelleted high-grain diet (HG), and a pelleted high-grain diet (HP). After 60 days of treatment, ileal mucosal samples were collected for microbiome and metabolome analysis. The results of principal coordinate analysis and permutation multivariate analysis showed that there was a tendency for microbial differentiation between the CON and HG groups (P < 0.1), although no significant difference between the HG and HP groups was observed (P > 0.05). Compared with the CON diet, the HG diet decreased (P < 0.05) the abundance of some probiotic species (e.g., Sphingomonas and Candidatus Arthromitus) and increased (P < 0.05) the abundance of acid-producing microbiota (e.g., Succiniclasticum, Nesterenkonia, and Alloprevotella) in the ileal mucosa. Compared with the HG diet, the HP diet decreased (P < 0.05) the abundance of Alloprevotella and increased (P < 0.05) the abundance of Mycoplasma in the ileal mucosa. Furthermore, partial least squares discriminant analysis and orthogonal partial least-squared discriminant analysis indicated that different dietary treatments resulted in different metabolic patterns in the ileal mucosa of the CON, HG, and HP groups. The HG diet altered (VIP > 1 and P < 0.05) the metabolic patterns of amino acids, fatty acids, and nucleotides/nucleosides (such as increased amounts of ornithine, tyrosine, cis-9-palmitoleic acid, and adenosine) compared with the CON diet. However, 10 differential metabolites (VIP > 1 and P < 0.05; including tyrosine, ornithine, and cis-9-palmitoleic acid) identified in the HG group exhibited a diametrically opposite trend in the HP group, suggesting that the HP diet could partially eliminate the changes brought upon by the HG diet. Collectively, our findings demonstrate that different diets altered the ileal mucosal microbiota and metabolites and provide new insight into the effects of high-grain diets on the intestinal health of ruminant animals.

RevDate: 2021-09-13

Tavares TCL, Bezerra WM, Normando LRO, et al (2021)

Brazilian Semi-Arid Mangroves-Associated Microbiome as Pools of Richness and Complexity in a Changing World.

Frontiers in microbiology, 12:715991.

Mangrove microbiomes play an essential role in the fate of mangroves in our changing planet, but the factors regulating the biogeographical distribution of mangrove microbial communities remain essentially vague. This paper contributes to our understanding of mangrove microbiomes distributed along three biogeographical provinces and ecoregions, covering the exuberant mangroves of Amazonia ecoregion (North Brazil Shelf) as well as mangroves located in the southern limit of distribution (Southeastern ecoregion, Warm Temperate Southwestern Atlantic) and mangroves localized on the drier semi-arid coast (Northeastern ecoregion, Tropical Southwestern Atlantic), two important ecotones where poleward and landward shifts, respectively, are expected to occur related to climate change. This study compared the microbiomes associated with the conspicuous red mangrove (Rhizophora mangle) root soils encompassing soil properties, latitudinal factors, and amplicon sequence variants of 105 samples. We demonstrated that, although the northern and southern sites are over 4,000 km apart, and despite R. mangle genetic divergences between north and south populations, their microbiomes resemble each other more than the northern and northeastern neighbors. In addition, the northeastern semi-arid microbiomes were more diverse and displayed a higher level of complexity than the northern and southern ones. This finding may reflect the endurance of the northeast microbial communities tailored to deal with the stressful conditions of semi-aridity and may play a role in the resistance and growing landward expansion observed in such mangroves. Minimum temperature, precipitation, organic carbon, and potential evapotranspiration were the main microbiota variation drivers and should be considered in mangrove conservation and recovery strategies in the Anthropocene. In the face of changes in climate, land cover, biodiversity, and chemical composition, the richness and complexity harbored by semi-arid mangrove microbiomes may hold the key to mangrove adaptability in our changing planet.

RevDate: 2021-09-13

Xia X, Ni J, Yin S, et al (2021)

Elevated Systemic and Intestinal Inflammatory Response Are Associated With Gut Microbiome Disorder After Cardiovascular Surgery.

Frontiers in microbiology, 12:686648.

Systemic inflammatory response after cardiovascular surgery is associated with poor prognosis, to which gut barrier impairment is related. To investigate whether perioperative changes of the gut microbiome are associated with systemic and intestinal inflammatory response, we examined changes of the gut microbiome, intestinal homeostasis, and systemic inflammatory response in cardiovascular patients before (Pre) surgery and on the first defecation day [postoperative time 1 (Po1)] or a week [postoperative time 2 (Po2)] postsurgery. Markedly, the enhanced systemic inflammatory response was observed in Po1 and Po2 compared with that in Pre. In line with inflammatory response, impaired gut barrier and elevated gut local inflammation were observed in Po1 and Po2. Microbiome analysis showed a remarkable and steady decline of alpha diversity perioperatively. In addition, microbial composition in the postoperation period was characterized by significant expansion of Enterococcus along with a decrease in anaerobes (Blautia, Faecalibacterium, Bifidobacterium, Roseburia, Gemmiger, [Ruminococcus], and Coprococcus), which were typically health-associated bacteria. Spearman correlation analysis showed microbiome disorder was associated with enhanced systemic inflammatory response and intestinal dysbiosis. These results suggest that microbiome disorder was related to disturbed gut homeostatic and subsequently elevates plasma endotoxin and systemic inflammatory response after cardiovascular surgery. This study not only highlights gut microbiome would be considered in future clinical practice but also proposes a promising perspective of potential diagnostic and therapeutic options for perioperative management of cardiovascular surgery patients.

RevDate: 2021-09-13

Bakir-Gungor B, Bulut O, Jabeer A, et al (2021)

Discovering Potential Taxonomic Biomarkers of Type 2 Diabetes From Human Gut Microbiota via Different Feature Selection Methods.

Frontiers in microbiology, 12:628426.

Human gut microbiota is a complex community of organisms including trillions of bacteria. While these microorganisms are considered as essential regulators of our immune system, some of them can cause several diseases. In recent years, next-generation sequencing technologies accelerated the discovery of human gut microbiota. In this respect, the use of machine learning techniques became popular to analyze disease-associated metagenomics datasets. Type 2 diabetes (T2D) is a chronic disease and affects millions of people around the world. Since the early diagnosis in T2D is important for effective treatment, there is an utmost need to develop a classification technique that can accelerate T2D diagnosis. In this study, using T2D-associated metagenomics data, we aim to develop a classification model to facilitate T2D diagnosis and to discover T2D-associated biomarkers. The sequencing data of T2D patients and healthy individuals were taken from a metagenome-wide association study and categorized into disease states. The sequencing reads were assigned to taxa, and the identified species are used to train and test our model. To deal with the high dimensionality of features, we applied robust feature selection algorithms such as Conditional Mutual Information Maximization, Maximum Relevance and Minimum Redundancy, Correlation Based Feature Selection, and select K best approach. To test the performance of the classification based on the features that are selected by different methods, we used random forest classifier with 100-fold Monte Carlo cross-validation. In our experiments, we observed that 15 commonly selected features have a considerable effect in terms of minimizing the microbiota used for the diagnosis of T2D and thus reducing the time and cost. When we perform biological validation of these identified species, we found that some of them are known as related to T2D development mechanisms and we identified additional species as potential biomarkers. Additionally, we attempted to find the subgroups of T2D patients using k-means clustering. In summary, this study utilizes several supervised and unsupervised machine learning algorithms to increase the diagnostic accuracy of T2D, investigates potential biomarkers of T2D, and finds out which subset of microbiota is more informative than other taxa by applying state-of-the art feature selection methods.

RevDate: 2021-09-13

Zhang L, Yang C, Li Y, et al (2021)

Dynamic Changes in the Levels of Amyloid-β42 Species in the Brain and Periphery of APP/PS1 Mice and Their Significance for Alzheimer's Disease.

Frontiers in molecular neuroscience, 14:723317.

Although amyloid-β42 (Aβ42) has been used as one of the core biomarkers for Alzheimer's disease (AD) diagnosis, the dynamic changes of its different forms in the brain, blood, and even intestines and its correlation with the progression of AD disease remain obscure. Herein, we screened Aβ42-specific preferred antibody pairs 1F12/1F12 and 1F12/2C6 to accurately detect Aβ42 types using sandwich ELISA, including total Aβ42, Aβ42 oligomers (Aβ42Os), and Aβ42 monomers (Aβ42Ms). The levels of Aβ42 species in the brain, blood, and intestines of different aged APP/PS1 mice were quantified to study their correlation with AD progression. Total Aβ42 levels in the blood were not correlated with AD progression, but Aβ42Ms level in the blood of 9-month-old APP/PS1 mice was significantly reduced, and Aβ42Os level in the brain was significantly elevated compared to 3-month-old APP/PS1, demonstrating that the levels of Aβ42Ms and Aβ42Os in the blood and brain were correlated with AD progression. Interestingly, in 9-month-old APP/PS1 mice, the level of Aβ42 in the intestine was higher than that in 3-month-old APP/PS1 mice, indicating that the increased level of Aβ42 in the gastrointestinal organs may also be related to the progression of AD. Meanwhile, changes in the gut microbiota composition of APP/PS1 mice with age were also observed. Therefore, the increase in Aβ derived from intestinal tissues and changes in microbiome composition can be used as a potential early diagnosis tool for AD, and further used as an indicator of drug intervention to reduce brain amyloid.

RevDate: 2021-09-13

Hill AE, Wade-Martins R, PWJ Burnet (2021)

What Is Our Understanding of the Influence of Gut Microbiota on the Pathophysiology of Parkinson's Disease?.

Frontiers in neuroscience, 15:708587.

Microbiota have increasingly become implicated in predisposition to human diseases, including neurodegenerative disorders such as Parkinson's disease (PD). Traditionally, a central nervous system (CNS)-centric approach to understanding PD has predominated; however, an association of the gut with PD has existed since Parkinson himself reported the disease. The gut-brain axis refers to the bidirectional communication between the gastrointestinal tract (GIT) and the brain. Gut microbiota dysbiosis, reported in PD patients, may extend this to a microbiota-gut-brain axis. To date, mainly the bacteriome has been investigated. The change in abundance of bacterial products which accompanies dysbiosis is hypothesised to influence PD pathophysiology via multiple mechanisms which broadly centre on inflammation, a cause of alpha-synuclein (a-syn) misfolding. Two main routes are hypothesised by which gut microbiota can influence PD pathophysiology, the neural and humoral routes. The neural route involves a-syn misfolding peripherally in the enteric nerves which can then be transported to the brain via the vagus nerve. The humoral route involves transportation of bacterial products and proinflammatory cytokines from the gut via the circulation which can cause central a-syn misfolding by inducing neuroinflammation. This article will assess whether the current literature supports gut bacteria influencing PD pathophysiology via both routes.

RevDate: 2021-09-13

Kelly MS, Plunkett C, Yu Y, et al (2021)

Non-diphtheriae Corynebacterium species are associated with decreased risk of pneumococcal colonization during infancy.

The ISME journal [Epub ahead of print].

Streptococcus pneumoniae (pneumococcus) is a leading cause of severe infections among children and adults. Interactions between commensal microbes in the upper respiratory tract and S. pneumoniae are poorly described. In this study, we sought to identify interspecies interactions that modify the risk of S. pneumoniae colonization during infancy and to describe development of the upper respiratory microbiome during infancy in a sub-Saharan African setting. We collected nasopharyngeal swabs monthly (0-6 months of age) or bimonthly (6-12 months of age) from 179 mother-infant dyads in Botswana. We used 16S ribosomal RNA gene sequencing to characterize the nasopharyngeal microbiome and identified S. pneumoniae colonization using a species-specific PCR assay. We detect S. pneumoniae colonization in 144 (80%) infants at a median age of 71 days and identify a strong negative association between the relative abundance of the bacterial genera Corynebacterium within the infant nasopharyngeal microbiome and the risk of S. pneumoniae colonization. Using in vitro cultivation experiments, we demonstrate growth inhibition of S. pneumoniae by secreted factors from strains of several Corynebacterium species isolated from these infants. Finally, we demonstrate that antibiotic exposures and the winter season are associated with a decline in the relative abundance of Corynebacterium within the nasopharyngeal microbiome, while breastfeeding is associated with an increase in the Corynebacterium relative abundance. Our findings provide novel insights into the interspecies interactions that contribute to colonization resistance to S. pneumoniae and suggest that the nasopharyngeal microbiome may be a previously unrecognized mechanism by which environmental factors influence the risk of pneumococcal infections during childhood. Moreover, this work lays the foundation for future studies seeking to use targeted manipulation of the nasopharyngeal microbiome to prevent infections caused by S. pneumoniae.

RevDate: 2021-09-13

Baky MH, Elshahed MS, Wessjohann LA, et al (2021)

Interactions between dietary flavonoids and the gut microbiome: A comprehensive review.

The British journal of nutrition pii:S0007114521003627 [Epub ahead of print].

Flavonoids are natural polyphenol secondary metabolites that are widely produced in planta. Flavonoids are ubiquities in human dietary intake and exhibit a myriad of health benefits. Flavonoids-induced biological activities are strongly influenced by their in-situ availability in the human GI tract, as well as the levels of which are modulated by interaction with the gut bacteria. As such, assessing flavonoids-microbiome interactions is considered a key to understand their physiological activities. Here, we review the interaction between the various classes of dietary flavonoids (flavonols, flavones, flavanones, isoflavones, flavan-3-ols, and anthocyanins) and gut microbiota. We aim to provide a holistic overview of the nature and identity of flavonoids on diet, and highlight how flavonoids chemical structure, metabolism, and impact on humans and their microbiomes are interconnected. Emphasis is placed on how flavonoids and their biotransformation products affect gut microbiota population, influence gut homeostasis, and induce measurable physiological changes and biological benefits.

RevDate: 2021-09-12

Yan K, Hung A, Parmer C, et al (2021)

Obeticholic Acid Decreases Intestinal Content of Enterococcus in Rats With Cirrhosis and Ascites.

Hepatology communications, 5(9):1507-1517.

The intestinal microbiome and bacterial translocation (BT), the passage of microorganisms from the gut lumen to mesenteric lymph nodes and other extra-intestinal sites, are main mechanisms implicated in liver injury and further decompensation in patients with cirrhosis. We hypothesized that obeticholic acid (OCA), a semisynthetic bile acid, would change the microbiome composition and reduce bacterial translocation in experimental cirrhosis. Rats with cirrhosis induced by carbon tetrachloride inhalation (a nonseptic model) with ascites present for at least 7 days were randomized to receive a 14-day course of OCA at a dose of 5 mg/kg/day (n = 34) or placebo (n = 34). Stool was collected at days 1 (randomization), 8, and 14 (sacrifice) for analysis of intestinal microbiome using the V4 hypervariable region of the bacterial 16S gene amplified by polymerase chain reaction. Bacteriological cultures of mesenteric lymph nodes, blood, and ascites were performed at end of study. Twenty-four animals in each group reached the end of study. Compared with placebo, rats treated with OCA had decreased relative abundance of Enterococcus in both ileum content (P = 0.02) and in stool (P < 0.001). BT from pathogenic bacteria was not different between groups. At end of treatment, rats on OCA had a significantly lower aspartate aminotransferase (AST) (266 vs. 369 IU/L; P < 0.01) and higher serum albumin (0.9 vs. 0.7 g/dL; P < 0.01) than rats on placebo. Conclusion: Although OCA did not appear to reduce BT by pathogenic bacteria, the reduction in intestinal content of Enterococcus, which has been associated with hepatocyte death, in OCA-treated animals is consistent with our observed improvements in AST and in liver function, as evidenced by higher serum albumin.

RevDate: 2021-09-12

Rangel LI, Hamilton O, de Jonge R, et al (2021)

Fungal social influencers: secondary metabolites as a platform for shaping the plant-associated community.

The Plant journal : for cell and molecular biology [Epub ahead of print].

Fungal secondary metabolites (FSMs) are capable of manipulating plant community dynamics by inhibiting or facilitating the establishment of co-habitating organisms. Although production of FSMs is not crucial for survival of the producer, their absence can indirectly impair growth and/or niche competition of these fungi on the plant. Presence of FSMs with no obvious consequence on the fitness of the producer leaves questions regarding ecological impact. This review investigates how fungi employ FSMs as a platform to mediate fungal-fungal, fungal-bacterial, and fungal-animal interactions associated with the plant community. We discuss how the biological function of FSMs may indirectly benefit the producer by altering the dynamics of surrounding organisms. We introduce several instances where FSMs influence antagonistic- or alliance-driven interactions. Part of our aim is to decipher the meaning of the FSM 'language' since it is widely noted to impact the surrounding community. Here, we highlight the contribution of FSMs to plant-associated interaction networks that affect the host either broadly or in ways that may have previously been unclear.

RevDate: 2021-09-12

Wang Y, Zhang J, Deji C, et al (2021)

Differential perturbations of gut microbial profiles and co-occurrence networks among phases of methamphetamine-induced conditioned place preference.

Journal of neuroscience research [Epub ahead of print].

The gut-brain axis provides a pathway for the interaction between gut microbiota and methamphetamine (METH) addiction. However, the gut microbial signatures during different phases of METH use remain unclear. In the present study, we established models of acquisition, extinction, and reinstatement of METH-induced conditioned place preference (CPP) in male mice and detected the gut microbiome profiles of the fecal samples at the three phases by 16S rRNA gene sequencing. Our results revealed that the richness of the gut microbiome increased following repeated METH administration, and it decreased after 4 weeks of abstinence. The microbial richness remained at a low level after one METH challenge at the reinstatement phase. The abundance of several genera including Prevotella, Bacteroides, and Lactobacillus differentially altered among phases of METH-induced CPP. The co-occurrence networks of the gut microbiome became weaker and more unstable during the development of METH-induced CPP at the extinction and reinstatement phases. Notably, the predicted gene functions of short-chain fatty acid metabolism, which were correlated with the abundance of Prevotella, Bacteroides, and Lactobacillus, were found differentially enriched among phases of METH-induced CPP. Our findings highlight a potential association between perturbations of the gut microbiome and different phases of METH use.

RevDate: 2021-09-12

Kelleher ST, McMahon CJ, A James (2021)

Necrotizing Enterocolitis in Children with Congenital Heart Disease: A Literature Review.

Pediatric cardiology [Epub ahead of print].

Infants with congenital heart disease (CHD) are at an increased risk of developing necrotising enterocolitis (NEC), a serious inflammatory intestinal condition classically associated with prematurity. CHD not only increases the risk of NEC in preterm infants but is one of the most commonly implicated risk factors in term infants. Existing knowledge on the topic is limited largely to retrospective studies. This review acts to consolidate existing knowledge on the topic in terms of disease incidence, pathophysiology, risk factors, outcomes and the complex relationship between NEC and enteral feeds. Potential preventative strategies, novel biomarkers for NEC in this population, and the role of the intestinal microbiome are all explored. Numerous challenges exist in the study of this complex multifactorial disease which arise from the heterogeneity of the affected population and its relative scarcity. Nevertheless, its high related morbidity and mortality warrant renewed interest in identifying those infants most at risk and implementing strategies to reduce the incidence of NEC in infants with CHD.

RevDate: 2021-09-12

LeMay-Nedjelski L, Yonemitsu C, Asbury MR, et al (2021)

Oligosaccharides and Microbiota in Human Milk Are Interrelated at 3 Months Postpartum in a Cohort of Women with a High Prevalence of Gestational Impaired Glucose Tolerance.

The Journal of nutrition pii:6369047 [Epub ahead of print].

BACKGROUND: Human milk is a rich source of human milk oligosaccharides (HMOs) and bacteria. It is unclear how these components interact within the breast microenvironment.

OBJECTIVES: The objectives were first, to investigate the association between maternal characteristics and HMOs, and second, to assess the association between HMOs and microbial community composition and predicted function in milk from women with high rates of gestational glucose intolerance.

METHODS: This was an exploratory analysis of a previously completed prospective cohort study (NCT01405547) where milk samples (n = 107) were collected at 3 mo postpartum. Milk microbiota composition was analyzed by V4-16S ribosomal RNA gene sequencing and HMOs by rapid high-throughput HPLC. Data were stratified and analyzed by maternal secretor status phenotype and associations between HMOs and microbiota were determined using linear regression models (ɑ-diversity), Adonis (B-diversity), Poisson regression models (differential abundance), and general linear models (predicted microbial function).

RESULTS: Prepregnancy BMI, race, and frequency of direct breastfeeding, but not gestational glucose intolerance, were found to be significantly associated with a number of HMOs among secretors and non-secretors. Fucosyllacto-N-hexaose was negatively associated with microbial richness (Chao1) among secretors [B-estimate (SE): -9.3 × 102 (3.4 × 102); P = 0.0082] and difucosyllacto-N-hexaose was negatively associated with microbiota diversity (Shannon index) [-1.7 (0.78); P = 0.029] among secretors. Lacto-N-neotetraose (LNnT) was associated with both microbial B-diversity (weighted UniFrac R2 = 0.040, P = 0.036) and KEGG ortholog B-diversity (Bray-Curtis R2 = 0.039, P = 0.043) in secretors. Additionally, difucosyllactose in secretors and disialyllacto-N-hexaose and LNnT in non-secretors were associated with enrichment of predicted microbial genes encoding for metabolism- and infection-related pathways (P-false discovery rate < 0.1).

CONCLUSIONS: HMOs are associated with the microbial composition and predicted microbial functions in human milk at 3 mo postpartum. Further research is needed to investigate the role these relations play in maternal and infant health.

RevDate: 2021-09-12

Reyes SM, Allen DL, Williams JE, et al (2021)

Pumping supplies alter the microbiome of pumped human milk: An in-home, randomized, crossover trial.

The American journal of clinical nutrition pii:6369099 [Epub ahead of print].

BACKGROUND: The human milk microbiome may contribute to the benefits of breastfeeding by providing bacteria to the infant gastrointestinal tract. Many women pump their milk, but the effect of pumping on the milk microbiome is unknown.

OBJECTIVES: Our objective was to determine the effects of pumping supplies on the pumped human milk microbiome.

METHODS: This was an in-home, randomized, crossover trial of 2 collection methods. Women (n = 52) pumped twice within 3.5 h, once with their own breast pumps and milk collection supplies (OWN SUPP) and once with a hospital-grade pump and sterile collection supplies (STER SUPP). Pumping order was randomized. The milk microbiome was characterized by aerobic culturing and 16S ribosomal RNA gene sequencing.

RESULTS: Milk collected with OWN SUPP yielded more total aerobic and gram-negative bacteria than milk collected with STER SUPP, reflecting a 6.6 (adjusted OR; 95% CI: 1.7, 25; P = 0.006) higher odds of containing >104 total aerobic CFU/mL and 19 (adjusted OR; 95% CI: 4.1, 88; P < 0.0001) higher odds of yielding culturable gram-negative bacteria. Milk collected with OWN SUPP yielded more Proteobacterias , including higher relative abundances of Acinetobacter and Stenotrophomonas, compared to milk collected with STER SUPP. Results were consistent across pumping-order groups.

CONCLUSIONS: We demonstrated that pumping supplies altered the milk microbiome. On average, milk collected with OWN SUPP resulted in elevated levels of culturable total and gram-negative bacteria and proteobacterial DNA compared to milk collected with STER SUPP. More research is needed to assess implications for infant health.

RevDate: 2021-09-12

Houf J (2021)

Faecal microbiota transplants: towards a healthy disgust scepticism.

Medical humanities pii:medhum-2020-012135 [Epub ahead of print].

This paper engages with the obstacle of disgust surrounding the use of faecal microbiota transplants (FMT). In discourse about the human microbiome and microbiota-based therapies (like FMT), disgust has become an unavoidable emotion for physicians, patients and caregivers interested in these therapies. Additionally, microbiota therapies and microbiomes are challenging our conception of an individual biological self. As these two discourses converge with FMT, it becomes necessary to understand how they are working together. To do this, this paper explores the way disgust functions in the formation of subjects. Scholarship about disgust can be categorised into two approaches: disgust as a deep wisdom or disgust scepticism. The former approach focuses on the physiological, embodied aspects of our disgust reactions as evidence of 'truth' in disgusting encounters, and the latter recognises the way disgust is culturally contingent and adapted for use in moral and social determinations of good and bad. However, both positions accept the use of disgust as a defence against 'toxins and diseases'. Yet, as this paper argues, we should take the sceptical approach further. The disgust sceptical approach, particularly as developed by Sarah Ahmed, does more than just challenge disgust's role in moral deliberations. It also demands sceptical reflection on disgust as a universal defence against 'toxins and diseases'. Much as disgust can be co-opted to support oppression, it too can be co-opted to reconstitute a false vision of human subjectivity-the coherent, contained and exceptional human subject situated above the natural world. The human microbiome, faecal therapeutics and being disgusted give us an opportunity to recognise ourselves as more-than-human subjects.

RevDate: 2021-09-12

do Carmo Precci Lopes A, Ebner C, Gerke F, et al (2021)

Residual municipal solid waste as co-substrate at wastewater treatment plants: An assessment of methane yield, dewatering potential and microbial diversity.

The Science of the total environment, 804:149936 pii:S0048-9697(21)05011-7 [Epub ahead of print].

Separately collected organic fraction of municipal solid waste, also known as biowaste, is typically used to fill the available capacity of digesters at wastewater treatment plants. However, this approach might impair the use of the ensuing digestate for fertilizer production due to the presence of sewage sludge, a contaminated substrate. Worldwide, unsorted municipal solid household waste, i.e. residual waste, is still typically disposed of in landfills or incinerated, despite its high content of biodegradables and recyclables. Once efficiently separated from residual waste by mechanical processes, the biodegradables might be appropriate to substitute biowaste at wastewater treatment plants. Thus, the biowaste would be available for fertilizer production and contribute to a reduction in the demand on non-renewable fertilizers. This study aimed at determining the technical feasibility of co-digesting the mechanically separated organic fraction of residual waste with sewage sludge. Further, key parameters for the implementation of co-digestion at wastewater treatment plants were determined, namely, degradation of the solids and organics, specific methane production, flocculant demand, and dewatered sludge production. The microbial community and diversity in both mono- and co-digestion was also investigated. Semi-continuous laboratory scale experiments showed that the co-substrate derived from the residual waste provided a stable anaerobic co-digestion process, producing 206 to 245 L of methane per kg of volatiles solids added to the digester. The dewaterability of the digestate increased by 4.8 percentage points when the co-substrate was added; however, there was also an increase in the flocculant demand. The specific dewatered sludge production was 955 kg per ton of total solids of co-substrate added to the digester. Amplicon sequencing analysis provided a detailed insight into the microbial communities, which were primarily affected by the addition of co-substrate. The microbiota was fully functional and no inhibition or problems in the anaerobic digestion process were observed after co-substrate addition.

RevDate: 2021-09-12

Pereira AM, A Clemente (2021)

Dogs' microbiome from tip to toe.

Topics in companion animal medicine pii:S1938-9736(21)00077-5 [Epub ahead of print].

Microbiota and microbiome, which refers, respectively, to the microorganisms and conjoint of microorganisms and genes are known to live in symbiosis with hosts, being implicated in health and disease. The advancements and cost reduction associated with high-throughput sequencing techniques have allowed expanding the knowledge of microbial communities in several species, including dogs. Throughout their body, dogs harbor distinct microbial communities according to the location (e.g., skin, ear canal, conjunctiva, respiratory tract, genitourinary tract, gut), which have been a target of study mostly in the last couple of years. Although there might be a core microbiota for different body sites, shared by dogs, it is likely influenced by intrinsic factors such as age, breed, and sex, but also by extrinsic factors such as the environment (e.g., lifestyle, urban vs rural), and diet. It starts to become clear that some medical conditions are mediated by alterations in microbiota namely dysbiosis. Moreover, understanding microbial colonization and function can be used to prevent medical conditions, for instance, modulation of gut microbiota of puppies is more effective to ensure a healthy gut than interventions in adults. This paper gathers current knowledge of dogs' microbial communities, exploring their function, implications in the development of diseases, and potential interactions among communities while providing hints for further research.

RevDate: 2021-09-12

Tan S, Xu X, Cheng H, et al (2021)

The alteration of gut microbiome community play an important role in mercury biotransformation in largemouth bass.

Environmental research pii:S0013-9351(21)01321-9 [Epub ahead of print].

Mercury (Hg) biotransformation is an important process that can affect the speciation and bioaccumulation of Hg in fish. The intestinal microbiota has been suggested to take part in this process. However, Hg biotransformation in fish is still unclear and the responses of gut microbiota to different Hg exposure scenarios have not been well addressed. The present study investigated the bioaccumulation and biotransformation of Hg in a freshwater fish (Micropterus salmoides) and characterized the gut microbiome community under dietary inorganic Hg (IHg) or methylmercury (MeHg) exposure, aiming to evaluate the effects of gut microbiome's activities on the internal-handling and fate of Hg in fish. Significant Hg methylation was observed in fish under IHg exposure, whereas there was no demethylation occurred in MeHg-treated fish. Both IHg and MeHg could significantly alter the community composition of gut microbiome. The administrated IHg in the food could enhance the growth of methylators, resulting in additional MeHg production in fish gut. However, abundance of demethylators was greatly decreased under either IHg or MeHg exposure, leading the demethylation process to be negligible. The results strongly suggested that the behaviors of gut bacterial community played an important role in the presence or absence of biotransformation processes. This study elucidated the importance of gut microbiome in Hg biotransformation process, and helped to develop a novel perspective to understand the Hg bioaccumulation of fish in realistic environment.

RevDate: 2021-09-12

Lin S, Zhang T, Zhu L, et al (2021)

Characteristic dysbiosis in gout and the impact of a uric acid-lowering treatment, febuxostat on the gut microbiota.

Journal of genetics and genomics = Yi chuan xue bao pii:S1673-8527(21)00193-4 [Epub ahead of print].

Gut dysbiosis is suggested to play a critical role in the pathogenesis of gout. The aim of our study was to identify the characteristic dysbiosis of the gut microbiota in gout patients and the impact of a commonly used uric acid-lowering treatment, febuxostat on gut microbiota in gout. 16S ribosomal RNA sequencing and metagenomic shotgun sequencing was performed on fecal DNA isolated from 38 untreated gout patients, 38 gout patients treated with febuxostat, and 26 healthy controls (HCs). A restriction of gut microbiota biodiversity was detected in the untreated gout patients, and the alteration was partly restored by febuxostat. Biochemical metabolic indexes involved in liver and kidney metabolism were significantly associated with the gut microbiota composition in gout patients. Functional analysis revealed that the gut microbiome of gout patients had an enriched function on carbohydrate metabolism but a lower potential for purine metabolism, which was comparatively enhanced in the febuxostat treated gout patients. A classification microbial model obtained a high mean area under the curve (AUC) up to 0.973. Therefore, gut dysbiosis characterizings gout could potentially serve as a noninvasive diagnostic tool for gout and may be a promising target of future preventive interventions.

RevDate: 2021-09-13

Kim YK, J Song (2021)

Therapeutic Applications of Resveratrol in Hepatic Encephalopathy through Its Regulation of the Microbiota, Brain Edema, and Inflammation.

Journal of clinical medicine, 10(17):.

Hepatic encephalopathy is a common complication in patients with liver cirrhosis and portosystemic shunting. Patients with hepatic encephalopathy present a variety of clinical features, including neuropsychiatric manifestations, cognitive dysfunction, impaired gut barrier function, hyperammonemia, and chronic neuroinflammation. These pathogeneses have been linked to various factors, including ammonia-induced oxidative stress, neuronal cell death, alterations in the gut microbiome, astrocyte swelling, and blood-brain barrier disruptions. Many researchers have focused on identifying novel therapeutics and prebiotics in the hope of improving the treatment of these conditions. Resveratrol is a natural polyphenic compound and is known to exert several pharmacological effects, including antioxidant, anti-inflammatory, and neuroprotective activities. Recent studies suggest that resveratrol contributes to improving the neuropathogenic effects of liver failure. Here, we review the current evidence describing resveratrol's effects in neuropathogenesis and its impact on the gut-liver axis relating to hepatic encephalopathy. We highlight the hypothesis that resveratrol exerts diverse effects in hepatic encephalopathy and suggest that these effects are likely mediated by changes to the gut microbiota, brain edema, and neuroinflammation.

RevDate: 2021-09-11

Kattner AA (2021)

We refuse to die.

This issue of the Biomedical Journal offers insights into the origin and consequences of different lymphoproliferative disorders and autoimmunity. Furthermore we learn about RASopathies, a group of congenital disorders that occur rather frequently. Then the current ELISA assays for measuring antibody avidity are critically examined, the relationship between female sex steroid hormones and cardiovascular disease is explored, and an assessment of persistent diarrhea as a leading cause of child death in India is performed. Additionally, there are several articles about COVID-19, presenting its connection to neutrophil recruitment and acute respiratory distress syndrome, as well as its relation to changes in the vascular glycocalyx. A COVID-19 case study from the emergency room is presented. We are also introduced to novel treatment approaches against COVID-19 like the construction of peptide-based vaccines, or targeting the respiratory tract microbiome. Finally, there is an assessment about how prepared medical students at a Taiwan University feel for independent practice, and another article about the treatment of intravascular large B cell lymphoma in a Taiwanese institution. Lastly, we discover possible surgery techniques in the case of external auditory canal osteoma.


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
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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 )