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Gut microbes are associated with the development of depression based on extensive evidence. However, previous studies have led to conflicting reports on this association, posing challenges to the application of gut bacteria in the diagnostics and treatment of depression. To minimise heterogenicity in data analysis, the present meta-analysis adopted a standardised bioinformatics and statistical pipeline to analyse 16S rRNA sequences of 1827 samples from eight different cohorts. Although changes in the overall bacterial community were identified by our meta-analysis, depressive-correlated changes in alpha-diversity were absent. Enrichment of Bacteroidetes, Parabacteroides, Barnesiella, Bacteroides, and Bacteroides vulgatus, along with depletion in Firmicutes, Dialister, Oscillospiraceae UCG 003 and UCG 002, and Bacteroides plebeius, were observed in depressive-associated bacteria. By contrast, elevated L-glutamine degradation, and reduced L-glutamate and L-isoleucine biosynthesis were identified in depressive-associated microbiomes. After systemically reviewing the data of these collected cohorts, we have established a bacterial classifier to identify depressive symptoms with AUC 0.834 and 0.685 in the training and external validation dataset, respectively. Moreover, a low-risk bacterial cluster for depressive symptoms was identified, which was represented by a lower abundance of Escherichia-Shigella, and a higher abundance of Faecalibacterium, Oscillospiraceae UCG 002, Ruminococcus, and Christensenellaceae R.7 group.

Gut microbes are associated with the development of depression based on extensive evidence. However, previous studies have led to conflicting reports on this association, posing challenges to the application of the gut microbiota in the diagnostics and treatment of depression. To minimize heterogenicity in data analysis, the present meta-analysis adopted a standardized bioinformatic and statistical pipeline to analyze 16s rRNA sequences of 1827 samples from 8 different cohorts. Although changes in the overall microbial community were identified by our meta-analysis, depressive-correlated changes in alpha-diversity were absent. Enrichment of Bacteroidetes, Parabacteroides, Barnesiella, Bacteroides, Alistipes inops, Bacteroides massiliensis, along with depletion in Firmicutes, Dialister and Bacteroides plebeius were observed in depressive-associated microbiota. By contrast, elevated L-glutamine degradation and reduced L-glutamate production and L-isoleucine biosynthesis were identified in depressive-associated microbiome. After systemically reviewing the data of these collected cohorts, we have established a microbial classifier to identify depressive symptoms with AUC > 78%. Moreover, a low-risk microbial cluster for depressive symptoms was identified, which presented by a lower abundance of Escherichia-Shigella, and a higher abundance of Faecalibacterium, Oscillospiraceae UCG 002, Ruminococcus and Christensenellaceae R.7 group.

Reference genomes are essential for metagenomic analyses and functional characterization of the human gut microbiota. We present the Culturable Genome Reference (CGR), a collection of 1,520 nonredundant, high-quality draft genomes generated from >6,000 bacteria cultivated from fecal samples of healthy humans. Of the 1,520 genomes, which were chosen to cover all major bacterial phyla and genera in the human gut, 264 are not represented in existing reference genome catalogs. We show that this increase in the number of reference bacterial genomes improves the rate of mapping metagenomic sequencing reads from 50% to >70%, enabling higher-resolution descriptions of the human gut microbiome. We use the CGR genomes to annotate functions of 338 bacterial species, showing the utility of this resource for functional studies. We also carry out a pan-genome analysis of 38 important human gut species, which reveals the diversity and specificity of functional enrichment between their core and dispensable genomes., A resource of >1,500 bacterial reference genomes sheds light on the human gut microbiome.

Most of the disease studies for the gut microbiome have collected cases and control samples from the elderly or the middle-aged. Despite general interest in microbiome health, it is not known how microbial biomarkers from metagenome-wide association studies (MWAS) would perform in a cohort of young individuals, who would be largely free of chronic diseases, as well as medication. Here we analyze high-depth fecal metagenomic shotgun sequencing for 2183 healthy adults with clinical parameters, diet, lifestyle, and metabolite measurements. We provide the first set of large-scale evidence for gut microbiome dysbiosis in hyperuricemia, which relates to meat intake. We build a cardiometabolic disease risk model based on gut microbes for initial screening in a young population and confirm the validity using external cohorts. Fecal bacteria that have been reported to be enriched in colorectal cancer (CRC) are found to correlate with methylhistidines, branched-chain amino acids (BCAA), aromatic amino acids and glutamic acid in these young individuals, which were validated by an additional cohort of 1404 individuals. Our comprehensive data suggest that the gut microbiome could show trends towards diseases years before onset, and the results lay the foundation for the design of larger screens for cardiometabolic diseases and CRC with clinically meaningful cutoffs.

More than a decade of gut microbiome studies have a common goal of improving human health. However, while most of the disease studies have focused on the elderly or the middle-aged, a reference cohort for the gut microbiome in young individuals has been lacking. It is also not clear what other omics data need to be measured to better understand the gut microbiome. Here, we present a cohort including 2183 adults with high-depth metagenomic shotgun sequencing data for the fecal microbiome and other omics data. In this multiomic cohort, we observe a number of vitamins, hormones, amino acids, and trace elements that correlated with the gut microbiome. Many of the associations are validated in an additional cohort consisting of 1404 individuals. Our comprehensive data are poised to provide advice to future populations and mechanistic study designs to better understand and manage our gut microbiome.

Background International travel could facilitate the spread of antimicrobial-resistant bacteria including extended spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E). Previous studies, which attempted to understand the role of gut microbiota in the acquisition of antimicrobial resistant bacteria during international travels, are limited to western travellers. Methods We established a prospective cohort of 90 Hong Kong travellers to investigate gut microbiota determinants and associated risk factors for the acquisition of ESBL-E. Baseline characteristics and travel-associated risk factors were gathered through questionnaires. Faecal samples were collected in 3-4 days before and after travel. Antimicrobial susceptibility of ESBL-E isolates was tested, and gut microbiota were profiled by 16S rDNA amplicon sequencing. Non-parametric tests were used to detect potential associations, and logistic regression models were used to quantify the associations. Random forest models were constructed to identify microbial predictors for ESBL-E acquisition. Results In total, 49 (54.4%) participants were tested negative for ESBL-E colonization before travel and were followed up after travel. A total of 60 ESBL-E isolates were cultured from 20 (40.8%) participants. Having low Actinobacteria richness and low abundance of short-chain fatty acid-producing bacteria in the gut microbiota before travel increased the risk of acquiring ESBL-E and the risk can be further exacerbated by eating raw seafood during travel. Besides, post-travel ESBL-E positive participants had increased abundances of several opportunistic pathogens such as Staphylococcus, Enterococcus, Escherichia/Shigella and Klebsiella. The random forest model integrating pre-travel microbiota and the identified travel-related risk factor could predict ESBL-E acquisition with an area under the curve of 75.4% (95% confidence interval: 57.9–93.0%). Conclusions In this study, we identified both travel-related risk factors and microbiota predictors for the risk of ESBL-E acquisition. Our results provide foundational knowledge for future developments of microbiota-based interventions to prevent ESBL-E acquisition during international travels.

Although gut microbiota has been suggested to play a role in disease phenotypes of Prader&ndash, Willi syndrome (PWS), little is known about its composition in affected children and how it relates to hyperphagia. This cross-sectional study aimed to characterize the gut bacterial and fungal communities of children with PWS, and to determine associations with hyperphagia. Fecal samples were collected from 25 children with PWS and 25 age-, sex-, and body mass index-matched controls. Dietary intake data, hyperphagia scores, and relevant clinical information were also obtained. Fecal bacterial and fungal communities were characterized by 16S rRNA and ITS2 sequencing, respectively. Overall bacterial &alpha, diversity and compositions of PWS were not different from those of the controls, but 13 bacterial genera were identified to be differentially abundant. Interestingly, the fungal community, as well as specific genera, were different between PWS and controls. The majority of the variation in the gut microbiota was not attributed to differences in dietary intake or the impact of genotype. Hyperphagia scores were associated with fungal &alpha, diversity and relative abundance of several taxa, such as Staphylococcus, Clostridium, SMB53, and Candida. Further longitudinal studies correlating changes in the microbiome with the degree of hyperphagia and studies integrating multi-omics data are warranted.

Gut microbiome influenced many aspects of host physiology and psychology. Vice versa, lifestyles factors such as exercise and healthy diet are ways to shape the gut microbiota towards balance. We observed two distinct microbe groups characterized by physical fitness in a multi-omic cohort of 2183 young subjects with metagenomics, national physique comprehensive test, lifestyle and metabolome data. The panel of bacterial taxa including Clostridium bolteae, Escherichia coli, Ruminococcus gnavus, Clostridium clostridioforme, Clostridium innocuum, Bacteroides cellulosilyticus and Oscillospiraceae, were consistently associated with most of the physical fitness. Clostridium species and trace element both increased in the individuals those tend to stay up late. Yogurt consumption was associated with Streptococcus thermophilus and Bifidobacterium animalis subsp. lactis in feces, which differed from potentially endogenous Bifidobacterium species that was associated with milk intake. Our large-scale analyses were poised to advise for a healthy gut microbiome through behavioural changes.

The root microbes play pivotal roles in plant productivity, nutrient uptakes, and disease resistance. The root microbial community structure has been extensively investigated by 16S/18S/ITS amplicons and metagenomic sequencing in crops and model plants. However, the functional associations between root microbes and host plant growth are poorly understood. This work investigates the root bacterial community of foxtail millet (Setaria italica) and its potential effects on host plant productivity. We determined the bacterial composition of 2882 samples from foxtail millet rhizoplane, rhizosphere and corresponding bulk soils from 2 well-separated geographic locations by 16S rRNA gene amplicon sequencing. We identified 16 109 operational taxonomic units (OTUs), and defined 187 OTUs as shared rhizoplane core OTUs. The β-diversity analysis revealed that microhabitat was the major factor shaping foxtail millet root bacterial community, followed by geographic locations. Large-scale association analysis identified the potential beneficial bacteria correlated with plant high productivity. Besides, the functional prediction revealed specific pathways enriched in foxtail millet rhizoplane bacterial community. We systematically described the root bacterial community structure of foxtail millet and found its core rhizoplane bacterial members. Our results demonstrated that host plants enrich specific bacteria and functions in the rhizoplane. The potentially beneficial bacteria may serve as a valuable knowledge foundation for bio-fertilizer development in agriculture.

More than a decade of gut microbiome studies have a common goal for human health. As most of the disease studies sample the elderly or the middle-aged, a reference cohort for young individuals has been lacking. It is also not clear what other omics data need to be measured to better understand the gut microbiome. Here we present high-depth metagenomic shotgun sequencing data for the fecal microbiome together with other omics data in a cohort of 2,183 adults, and observe a number of vitamins, hormones, amino acids and trace elements to correlate with the gut microbiome and cluster with T cell receptors. Associations with physical fitness, sleeping habits and dairy consumption are identified in this large multi-omic cohort. Many of the associations are validated in an additional cohort of 1,404 individuals. Our comprehensive data are poised to advise future study designs to better understand and manage our gut microbiome both in population and in mechanistic investigations.

The gut microbiota has been linked to cardiovascular diseases. However, the composition and functional capacity of the gut microbiome in relation to cardiovascular diseases have not been systematically examined. Here, we perform a metagenome-wide association study on stools from 218 individuals with atherosclerotic cardiovascular disease (ACVD) and 187 healthy controls. The ACVD gut microbiome deviates from the healthy status by increased abundance of Enterobacteriaceae and Streptococcus spp. and, functionally, in the potential for metabolism or transport of several molecules important for cardiovascular health. Although drug treatment represents a confounding factor, ACVD status, and not current drug use, is the major distinguishing feature in this cohort. We identify common themes by comparison with gut microbiome data associated with other cardiometabolic diseases (obesity and type 2 diabetes), with liver cirrhosis, and rheumatoid arthritis. Our data represent a comprehensive resource for further investigations on the role of the gut microbiome in promoting or preventing ACVD as well as other related diseases., The gut microbiota may play a role in cardiovascular diseases. Here, the authors perform a metagenome-wide association study on stools from individuals with atherosclerotic cardiovascular disease and healthy controls, identifying microbial strains and functions associated with the disease.

Nat. Biotechnol. 33, 1103–1108 (2015); published online 28 September 2015; corrected after print 18 December 2018 In the version of this article initially published, the y-axis numbering in Figure 1 was high by a factor of 10; the correct range is 0.5 to 2.5 million nonredundant genes. The error hasbeen corrected in the HTML and PDF versions of the article.

Background Roux-en-Y gastric bypass (RYGB) is an effective means to achieve sustained weight loss for morbidly obese individuals. Besides rapid weight reduction, patients achieve major improvements of insulin sensitivity and glucose homeostasis. Dysbiosis of gut microbiota has been associated with obesity and some of its co-morbidities, like type 2 diabetes, and major changes of gut microbial communities have been hypothesized to mediate part of the beneficial metabolic effects observed after RYGB. Here we describe changes in gut microbial taxonomic composition and functional potential following RYGB. Methods We recruited 13 morbidly obese patients who underwent RYGB, carefully phenotyped them, and had their gut microbiomes quantified before (n = 13) and 3 months (n = 12) and 12 months (n = 8) after RYGB. Following shotgun metagenomic sequencing of the fecal microbial DNA purified from stools, we characterized the gut microbial composition at species and gene levels followed by functional annotation. Results In parallel with the weight loss and metabolic improvements, gut microbial diversity increased within the first 3 months after RYGB and remained high 1 year later. RYGB led to altered relative abundances of 31 species (P

Ten supporting figures. A figure caption for each is given within the file. (PDF 716 kb)

International audience; The pig is a major species for livestock production and is also extensively used as the preferred model species for analyses of a wide range of human physiological functions and diseases1. The importance of the gut microbiota in complementing the physiology and genome of the host is now well recognized2. Knowledge of the functional interplay between the gut microbiota and host physiology in humans has been advanced by the human gut reference catalogue3,4. Thus, establishment of a comprehensive pig gut microbiome gene reference catalogue constitutes a logical continuation of the recently published pig genome5. By deep metagenome sequencing of faecal DNA from 287 pigs, we identified 7.7 million non-redundant genes representing 719 metagenomic species. Of the functional pathways found in the human catalogue, 96% are present in the pig catalogue, supporting the potential use of pigs for biomedical research. We show that sex, age and host genetics are likely to influence the pig gut microbiome. Analysis of the prevalence of antibiotic resistance genes demonstrated the effect of eliminating antibiotics from animal diets and thereby reducing the risk of spreading antibiotic resistance associated with farming systems.

Colorectal cancer, a commonly diagnosed cancer in the elderly, often develops slowly from benign polyps called adenoma. The gut microbiota is believed to be directly involved in colorectal carcinogenesis. The identity and functional capacity of the adenoma- or carcinoma-related gut microbe(s), however, have not been surveyed in a comprehensive manner. Here we perform a metagenome-wide association study (MGWAS) on stools from advanced adenoma and carcinoma patients and from healthy subjects, revealing microbial genes, strains and functions enriched in each group. An analysis of potential risk factors indicates that high intake of red meat relative to fruits and vegetables appears to associate with outgrowth of bacteria that might contribute to a more hostile gut environment. These findings suggest that faecal microbiome-based strategies may be useful for early diagnosis and treatment of colorectal adenoma or carcinoma.

The mouse gut microbiome is catalogued and compared to the human microbiome. We established a catalog of the mouse gut metagenome comprising ∼2.6 million nonredundant genes by sequencing DNA from fecal samples of 184 mice. To secure high microbiome diversity, we used mouse strains of diverse genetic backgrounds, from different providers, kept in different housing laboratories and fed either a low-fat or high-fat diet. Similar to the human gut microbiome, >99% of the cataloged genes are bacterial. We identified 541 metagenomic species and defined a core set of 26 metagenomic species found in 95% of the mice. The mouse gut microbiome is functionally similar to its human counterpart, with 95.2% of its Kyoto Encyclopedia of Genes and Genomes (KEGG) orthologous groups in common. However, only 4.0% of the mouse gut microbial genes were shared (95% identity, 90% coverage) with those of the human gut microbiome. This catalog provides a useful reference for future studies.

As there is no effective treatment for irritable bowel syndrome (IBS), many patients turn to traditional Chinese medicine (TCM) for possible cure. We investigated the therapeutic efficacy of an ancient herbal Chinese formula in patients with diarrhea-predominant IBS.This was a randomized double-blinded placebo-controlled trial. Chinese IBS patients with predominant diarrhea symptoms that fulfilled Rome II criteria were recruited. The diagnosis was verified by a TCM herbalist using TCM criteria. Eligible patients were randomized to receive a standard preparation of TCM extracts that contained 11 herbs or placebo with similar appearance and taste for 8 wk after a 2-wk run-in period. Patients were followed up for an additional 8 wk post-treatment. Primary outcome was patient's global symptom assessment. Other outcome measures included individual IBS symptom scores and health-related quality of life (short form 36).One hundred nineteen patients were randomized: 60 to receive TCM and 59 to receive placebo. There was no significant difference in the proportion of patients with global symptom improvement between the TCM and placebo groups at week 8 (35% vs 44.1%, p = 0.38) and at week 16 (31.7% vs 33.9%, p = 0.62). Moreover, there was no difference in individual symptom scores and the quality-of-life assessment between the two groups at all time points.The use of this herbal formulation for diarrhea-predominant IBS did not lead to global symptom improvement. Further controlled clinical studies may be necessary to characterize the role of TCM in the management of IBS.

To minimize the impact of antibiotics, gut microorganisms harbour and exchange antibiotics resistance genes, collectively called their resistome. Using shotgun sequencing-based metagenomics, we analysed the partial eradication and subsequent regrowth of the gut microbiota in 12 healthy men over a 6-month period following a 4-day intervention with a cocktail of 3 last-resort antibiotics: meropenem, gentamicin and vancomycin. Initial changes included blooms of enterobacteria and other pathobionts, such as Enterococcus faecalis and Fusobacterium nucleatum, and the depletion of Bifidobacterium species and butyrate producers. The gut microbiota of the subjects recovered to near-baseline composition within 1.5 months, although 9 common species, which were present in all subjects before the treatment, remained undetectable in most of the subjects after 180 days. Species that harbour β-lactam resistance genes were positively selected for during and after the intervention. Harbouring glycopeptide or aminoglycoside resistance genes increased the odds of de novo colonization, however, the former also decreased the odds of survival. Compositional changes under antibiotic intervention in vivo matched results from in vitro susceptibility tests. Despite a mild yet long-lasting imprint following antibiotics exposure, the gut microbiota of healthy young adults are resilient to a short-term broad-spectrum antibiotics intervention and their antibiotics resistance gene carriage modulates their recovery processes.