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Chronic kidney disease (CKD) patients have an increased risk of cardiovascular diseases (CVDs). The present study aimed to investigate the gut microbiota and blood trimethylamine-N-oxide concentration (TMAO) in Chinese CKD patients and explore the underlying explanations through the animal experiment. The median plasma TMAO level was 30.33 μmol/L in the CKD patients, which was significantly higher than the 2.08 μmol/L concentration measured in the healthy controls. Next-generation sequence revealed obvious dysbiosis of the gut microbiome in CKD patients, with reduced bacterial diversity and biased community constitutions. CKD patients had higher percentages of opportunistic pathogens from gamma-Proteobacteria and reduced percentages of beneficial microbes, such as Roseburia , Coprococcus , and Ruminococcaceae. The PICRUSt analysis demonstrated that eight genes involved in choline, betaine, L-carnitine and trimethylamine (TMA) metabolism were changed in the CKD patients. Moreover, we transferred faecal samples from CKD patients and healthy controls into antibiotic-treated C57BL/6 mice and found that the mice that received gut microbes from the CKD patients had significantly higher plasma TMAO levels and different composition of gut microbiota than did the comparative mouse group. Our present study demonstrated that CKD patients had increased plasma TMAO levels due to contributions from both impaired renal functions and dysbiosis of the gut microbiota.

Several studies in recent times have linked gut microbiome (GM) diversity to the pathogenesis of cancer and its role in disease progression through immune response, inflammation and metabolism modulation. This study focused on the use of network analysis and weighted gene co-expression network analysis (WGCNA) to identify the biological interaction between the gut ecosystem and its metabolites that could impact the immunotherapy response in non-small cell lung cancer (NSCLC) patients undergoing second-line treatment with anti-PD1. Metabolomic data were merged with operational taxonomic units (OTUs) from 16S RNA-targeted metagenomics and classified by chemometric models. The traits considered for the analyses were: (i) condition: disease or control (CTRLs), and (ii) treatment: responder (R) or non-responder (NR). Network analysis indicated that indole and its derivatives, aldehydes and alcohols could play a signaling role in GM functionality. WGCNA generated, instead, strong correlations between short-chain fatty acids (SCFAs) and a healthy GM. Furthermore, commensal bacteria such as Akkermansia muciniphila, Rikenellaceae, Bacteroides, Peptostreptococcaceae, Mogibacteriaceae and Clostridiaceae were found to be more abundant in CTRLs than in NSCLC patients. Our preliminary study demonstrates that the discovery of microbiota-linked biomarkers could provide an indication on the road towards personalized management of NSCLC patients.

Ulcerative colitis is a chronic inflammatory disease of the colon that carries a significant disease burden in children. Therefore, new therapeutic approaches are being explored to help children living with this disease. Fecal microbiota transplantation (FMT) has been successful in some children with ulcerative colitis. However, the mechanism of its therapeutic effect in this patient population is not well understood. To characterize changes in gut microbial and metabolomic profiles after FMT, we performed 16S rRNA gene sequencing, shotgun metagenomic sequencing, virome analysis and untargeted metabolomics by gas chromatography-time of flight-mass spectrometry on stool samples collected before and after FMT from four children with ulcerative colitis who responded to this treatment. Alpha diversity of the gut microbiota increased after intervention, with species richness rising from 251 (S.D. 125) to 358 (S.D. 27). In responders, the mean relative abundance of bacteria in the class Clostridia shifted toward donor levels, increasing from 33% (S.D. 11%) to 54% (S.D. 16%). Patient metabolomic and viromic profiles exhibited a similar but less pronounced shift toward donor profiles after FMT. The fecal concentrations of several metabolites were altered after FMT, correlating with clinical improvement. Larger studies using a similar multi-omics approach may suggest novel strategies for the treatment of pediatric ulcerative colitis.

An increasing number of evidences indicate microbes are implicated in human physiological mechanisms, including complicated disease pathology. Some microbes have been demonstrated to be associated with diverse important human diseases or disorders. Through investigating these disease-related microbes, we can obtain a better understanding of human disease mechanisms for advancing medical scientific progress in terms of disease diagnosis, treatment, prevention, prognosis and drug discovery. Based on the known microbe-disease association network, we developed a semi-supervised computational model of L aplacian R egularized L east S quares for H uman M icrobe– D isease A ssociation (LRLSHMDA) by introducing Gaussian interaction profile kernel similarity calculation and Laplacian regularized least squares classifier. LRLSHMDA reached the reliable AUCs of 0.8909 and 0.7657 based on the global and local leave-one-out cross validations, respectively. In the framework of 5-fold cross validation, average AUC value of 0.8794 +/−0.0029 further demonstrated its promising prediction ability. In case studies, 9, 9 and 8 of top-10 predicted microbes have been manually certified to be associated with asthma, colorectal carcinoma and chronic obstructive pulmonary disease by published literature evidence. Our proposed model achieves better prediction performance relative to the previous model. We expect that LRLSHMDA could offer insights into identifying more promising human microbe-disease associations in the future.

Background Yaks are able to utilize the gastrointestinal microbiota to digest plant materials. Although the cellulolytic bacteria in the yak rumen have been reported, there is still limited information on the diversity of the major microorganisms and putative carbohydrate-metabolizing enzymes for the degradation of complex lignocellulosic biomass in its gut ecosystem. Results Here, this study aimed to decode biomass-degrading genes and genomes in the yak fecal microbiota using deep metagenome sequencing. A comprehensive catalog comprising 4.5 million microbial genes from the yak feces were established based on metagenomic assemblies from 92 Gb sequencing data. We identified a full spectrum of genes encoding carbohydrate-active enzymes, three-quarters of which were assigned to highly diversified enzyme families involved in the breakdown of complex dietary carbohydrates, including 120 families of glycoside hydrolases, 25 families of polysaccharide lyases, and 15 families of carbohydrate esterases. Inference of taxonomic assignments to the carbohydrate-degrading genes revealed the major microbial contributors were Bacteroidaceae , Ruminococcaceae , Rikenellaceae , Clostridiaceae , and Prevotellaceae . Furthermore, 68 prokaryotic genomes were reconstructed and the genes encoding glycoside hydrolases involved in plant-derived polysaccharide degradation were identified in these uncultured genomes, many of which were novel species with lignocellulolytic capability. Conclusions Our findings shed light on a great diversity of carbohydrate-degrading enzymes in the yak gut microbial community and uncultured species, which provides a useful genetic resource for future studies on the discovery of novel enzymes for industrial applications.

The aim of this study was to determine the impact of different wheat bran fractions on the gut microbiota and fat binding capacity to explain their differential effects on metabolic and inflammatory disorders induced by a western diet (WD) in mice. Wheat bran derived arabinoxylan oligosaccharides (AXOS), a crude fraction of wheat bran (WB), or the same wheat bran with reduced particle size (WBs) were added to the WD of mice for 8 weeks. AXOS shifted the gut microbiota composition, blunted Clostridium and Turicibacter genera and strongly promoted Bifidobacterium and Butyricicoccus genera, independently of changes in gut antimicrobial peptide expression. AXOS was the most efficient to reduce adiposity. Only WB fraction promoted fat excretion and differed from the other fractions by the capacity to increase the Akkermansia genus and to counteract gut interleukin 1 beta (IL1β) overexpression. Strikingly, WBs promoted steatosis and adipose tissue inflammation, despite its ability -like WB- to increase bacterial diversity. In conclusion, wheat bran fractions differently affect metabolic and inflammatory disorders associated with WD feeding, depending on their particle size, their fat binding capacity and their influence on the gut microbiota. Those results might be useful to take into account in nutritional advices to control obesity.

Structurally-diversified bile acids (BAs) are involved in shaping of intestinal microbiota as well as absorption of dietary lipids. Taurocholic acid, a conjugated form of BA, has been reported to be a factor triggering germination of a wide range of spore-forming bacteria in intestine. To test a hypothesis that other BAs also promote germination of intestinal bacteria, we attempted culture of bacteria from ethanol-treated feces by using a series of BAs. It was found that conjugated-BAs, notably three glycine-conjugated BAs, glycodeoxycholic acid and glycochenodeoxycholic acid, significantly increased the number and the species variety of colonies formed on the agar plate. These colonized bacteria mostly belonged to class Clostridia, mainly consisting of families Lachnospiraceae, Clostridiaceae, and Peptostreptococcaceae. There were several types of bacteria associated with different sensitivity to each BA. Eventually, we isolated 72 bacterial species of which 61 are known and 11 novel. These results demonstrate that the culturable range of bacteria in intestine can be widened using the germination-inducing activity of BAs. This approach would advance the research on spore-forming Clostridia that contains important but difficult-to-cultured bacteria associate with host health and diseases.

Abstract Background Inflammatory bowel diseases (IBDs) are a group of heterogeneous inflammatory conditions affecting the gastrointestinal tract. Although there is considerable evidence linking the gut microbiota to intestinal inflammation, there is limited knowledge on its potential role in the development of extraintestinal manifestations of IBD. Methods Four groups of patients were included: IBD-associated arthropathy (IBD-A); IBD without arthropathy (IBD-N); rheumatoid arthritis (RA); and non-IBD, nonarthritis controls. DNA from stool samples was isolated and sequenced using the Illumina platform. Paired-end reads were quality-controlled using SHI7 and processed with SHOGUN. Abundance and diversity analyses were performed using QIIME, and compositional biomarker identification was performed using LEfSe. Results One hundred eighty patients were included in the analysis. IBD-A was associated with an increased abundance of microbial tyrosine degradation pathways when compared with IBD-N (P = 0.02), whereas IBD-A and RA patients both shared an increased abundance of Clostridiaceae when compared with controls (P = 0.045). We found that history of bowel surgery was a significant source of variability (P = 0.001) among all IBD patients and was associated with decreased alpha diversity and increased abundance of Enterobacteriaceae (P = 0.004). Conclusions An increased abundance of gut microbial tyrosine degradation pathways was associated with IBD-A. An increased abundance of Clostridiaceae was shared by both IBD-A and RA patients and suggests a potentially common microbial link for inflammatory arthritis. The increased abundance of Enterobacteriaceae, previously reported in IBD, may be due to the effects of previous bowel surgery and highlights the importance of controlling for this variable in future studies.

The Lachnospiraceae and Ruminococcaceae are two of the most abundant families from the order Clostridiales found in the mammalian gut environment, and have been associated with the maintenance of gut health. While they are both diverse groups, they share a common role as active plant degraders. By comparing the genomes of the Lachnospiraceae and Ruminococcaceae with the Clostridiaceae, a more commonly free-living group, we identify key carbohydrate-active enzymes, sugar transport mechanisms, and metabolic pathways that distinguish these two commensal groups as specialists for the degradation of complex plant material.

Pre-weaning diarrhea (PWD) in mink kits is a common multifactorial syndrome on commercial mink farms. Several potential pathogens such as astroviruses, caliciviruses, Escherichia coli and Staphylococcus delphini have been studied, but the etiology of the syndrome seems complex. In pooled samples from 38 diarrheic and 42 non-diarrheic litters, each comprising of intestinal contents from 2-3 mink kits from the same litter, the bacterial populations were studied using Illumina Next Generation Sequencing technology and targeted 16S amplicon sequencing. In addition, we used deep sequencing to determine and compare the viral intestinal content in 31 healthy non-diarrheic and 30 diarrheic pooled samples (2-3 mink kits from the same litter per pool). The results showed high variations in composition of the bacterial species between the pools. Enterococci, staphylococci and streptococci dominated in both diarrheic and non-diarrheic pools. However, enterococci accounted for 70% of the reads in the diarrheic group compared to 50% in the non-diarrheic group and this increase was at the expense of staphylococci and streptococci which together accounted for 45% and 17% of the reads in the non-diarrheic and diarrheic group, respectively. Moreover, in the diarrheic pools there were more reads assigned to Clostridia, Escherichia-Shigella and Enterobacter compared to the non-diarrheic pools. The taxonomically categorized sequences from the virome showed that the most prevalent viruses in all pools were caliciviruses and mamastroviruses (almost exclusively type 10). However, the numbers of reads assigned to caliciviruses were almost 3 times higher in the diarrheic pools compared the non-diarrheic pools and Sapporo-like caliciviruses were more abundant than the Norwalk-like caliciviruses. The results from this study have contributed to the insight into the changes in the intestinal microbiota associated with the PWD syndrome of mink.