An Expanded Gene Catalog of Mouse Gut Metagenomes

High-quality and comprehensive reference gene catalogs are essential for metagenomic research. The rather low diversity of samples used to construct existing catalogs of the mouse gut metagenome limits the numbers of identified genes in existing catalogs. We therefore established an expanded catalog of genes in the mouse gut metagenome (EMGC) containing >5.8 million genes by integrating 88 newly sequenced samples, 86 mouse gut-related bacterial genomes, and 3 existing gene catalogs. EMGC increases the number of nonredundant genes by more than 1 million genes compared to the so-far most extensive catalog. More than 60% of the genes in EMGC were assigned to Bacteria, with 54.20% being assigned to a phylum and 35.33% to a genus, while 30.39% were annotated at the KEGG orthology level. Nine hundred two metagenomic species (MGS) assigned to 122 taxa are identified based on the EMGC. The EMGC-based analysis of samples from groups of mice originating from different animal providers, housing laboratories, and genetic strains substantiated that diet is a major contributor to differences in composition and functional potential of the gut microbiota irrespective of differences in environment and genetic background. We envisage that EMGC will serve as a valuable reference data set for future metagenomic studies in mice.publishedVersio

Characterization a Novel Butyric Acid-Producing Bacterium Collinsella aerofaciens Subsp. Shenzhenensis Subsp. Nov.

Butyrate-producing bacteria can biosynthesize butyrate and alleviate inflammatory diseases. However, few studies have reported that the genus Collinsella has the ability to produce butyric acid. Here, our study depicts a Collinsella strain, which is a rod-shaped obligate anaerobe that is able to produce butyric acid. This microorganism was isolated from a human gut, and the optimal growth conditions were found to be 37 °C on PYG medium with pH 6.5. The 16S rRNA gene sequence demonstrated that this microorganism shared 99.93% similarity with C. aerofaciens ATCC 25986T, which was higher than the threshold (98.65%) for differentiating two species. Digital DNA–DNA hybridization and average nucleotide identity values also supported that this microorganism belonged to the species C. aerofaciens. Distinct phenotypic characteristics between TF06-26 and the type strain of C. aerofaciens, such as the fermentation of D-lactose, D-fructose and D-maltose, positive growth under pH 5 and 0.2% (w/v) cholate, suggested this strain was a novel subspecies. Comparative genome analysis revealed that butyric acid kinase and phosphate butyryltransferase enzymes were coded exclusively by this strain, indicating a specific butyric acid-producing function of this C. aerofaciens subspecies within the genus Collinsella. Thus, Collinsella aerofaciens subsp. shenzhenensis subsp. nov. was proposed, with set strain TF06-26T (=CGMCC 1.5216T = DSM 105138T) as the type strain

A Novel Gene Alignment in <i>Dorea</i> sp. AM58‑8 Produces 7‑Dehydroxy-3β Bile Acids from Primary Bile Acids

Bile acids are essential metabolites and signaling molecules in mammals. Primary bile acids are synthesized from cholesterol in the liver. At the same time, the microbiota in the mammalian gut has many interactions with bile acid, including various biotransformation processes such as 7-dehydroxylation and 3-epimerization. 7-Dehydroxylation is mediated by a bile acid-inducible (bai) operon, while 7-dehydroxylation and 3-epimerization are independently observed in only a few strains. Herein, we describe a novel microbe, Dorea sp. AM58-8, that can accomplish a two-step transformation and turn primary bile acids into both 3α secondary bile acids like deoxycholic acid and lithocholic acid, and 3β secondary bile acids like isodeoxycholic acid and isolithocholic acid. We subsequently characterized BaiA, BaiB, BaiE, and their substrate profiles biochemically. The potential bai gene clusters in the metagenomes were further mined. Their evolution, potential functions, and possible regulatory pathways were predicted using bioinformatics based on our understanding of the 7-dehydroxylation pathway in Dorea sp. AM58-8. This study of Dorea sp. AM58-8 also helps us distinguish the inactive bacteria that seem to have the 7-dehydroxylation pathway proteins and discover the 7-dehydroxylation pathway in other mammalian gut microbes

Fecal microbiota transplantation results in bacterial strain displacement in patients with inflammatory bowel diseases

Fecal microbiota transplantation (FMT), which is thought to have the potential to correct dysbiosis of gut microbiota, has been used to treat inflammatory bowel disease (IBD) for almost a decade. Here, we report an interventional prospective cohort study performed to elucidate the extent of and processes underlying microbiota engraftment in IBD patients after FMT treatment. The cohort included two categories of patients: (a) patients with moderate to severe Crohn’s disease (CD) (Harvey–Bradshaw Index ≥ 7, n = 11) and (b) patients with ulcerative colitis (UC) (Montreal classification S2 and S3, n = 4). All patients were treated with a single FMT (via mid‐gut, from healthy donors), and follow‐up visits were performed at baseline, 3 days, 1 week, and 1 month after FMT (missing time points included). At each follow‐up time point, fecal samples and clinical metadata were collected. For comparative analysis, 10 fecal samples from 10 healthy donors were included to represent the diversity level of normal gut microbiota. Additionally, the metagenomic data of 25 fecal samples from five individuals with metabolic syndrome who underwent autologous FMT treatment were downloaded from a previous published paper to represent fluctuations in microbiota induced during FMT. All fecal samples underwent shotgun metagenomic sequencing. We found that 3 days after FMT, 11 out of 15 recipients were in remission (three out of four UC recipients; 8 out of 11 CD recipients). Generally, bacterial colonization was observed to be lower in CD recipients than in UC recipients at both species and strain levels. Furthermore, across species, different strains displayed disease‐specific displacement advantages under two‐disease status. Finally, most post‐FMT species (> 80%) could be properly predicted (area under the curve > 85%) using a random forest classification model, with the gut microbiota composition and clinical parameters of pre‐FMT recipients acting as factors that contribute to prediction accuracy

Fecal microbiota transplantation results in bacterial strain displacement in patients with inflammatory bowel diseases

Fecal microbiota transplantation (FMT), which is thought to have the potential to correct dysbiosis of gut microbiota, has been used to treat inflammatory bowel disease (IBD) for almost a decade. Here, we report an interventional prospective cohort study performed to elucidate the extent of and processes underlying microbiota engraftment in IBD patients after FMT treatment. The cohort included two categories of patients: (a) patients with moderate to severe Crohn’s disease (CD) (Harvey–Bradshaw Index ≥ 7, n = 11) and (b) patients with ulcerative colitis (UC) (Montreal classification S2 and S3, n = 4). All patients were treated with a single FMT (via mid‐gut, from healthy donors), and follow‐up visits were performed at baseline, 3 days, 1 week, and 1 month after FMT (missing time points included). At each follow‐up time point, fecal samples and clinical metadata were collected. For comparative analysis, 10 fecal samples from 10 healthy donors were included to represent the diversity level of normal gut microbiota. Additionally, the metagenomic data of 25 fecal samples from five individuals with metabolic syndrome who underwent autologous FMT treatment were downloaded from a previous published paper to represent fluctuations in microbiota induced during FMT. All fecal samples underwent shotgun metagenomic sequencing. We found that 3 days after FMT, 11 out of 15 recipients were in remission (three out of four UC recipients; 8 out of 11 CD recipients). Generally, bacterial colonization was observed to be lower in CD recipients than in UC recipients at both species and strain levels. Furthermore, across species, different strains displayed disease‐specific displacement advantages under two‐disease status. Finally, most post‐FMT species (> 80%) could be properly predicted (area under the curve > 85%) using a random forest classification model, with the gut microbiota composition and clinical parameters of pre‐FMT recipients acting as factors that contribute to prediction accuracy

An Expanded Gene Catalog of Mouse Gut Metagenomes

High-quality and comprehensive reference gene catalogs are essential for metagenomic research. The rather low diversity of samples used to construct existing catalogs of the mouse gut metagenome limits the numbers of identified genes in existing catalogs. We therefore established an expanded catalog of genes in the mouse gut metagenome (EMGC) containing >5.8 million genes by integrating 88 newly sequenced samples, 86 mouse gut-related bacterial genomes, and 3 existing gene catalogs. EMGC increases the number of nonredundant genes by more than 1 million genes compared to the so-far most extensive catalog. More than 60% of the genes in EMGC were assigned to Bacteria, with 54.20% being assigned to a phylum and 35.33% to a genus, while 30.39% were annotated at the KEGG orthology level. Nine hundred two metagenomic species (MGS) assigned to 122 taxa are identified based on the EMGC. The EMGC-based analysis of samples from groups of mice originating from different animal providers, housing laboratories, and genetic strains substantiated that diet is a major contributor to differences in composition and functional potential of the gut microbiota irrespective of differences in environment and genetic background. We envisage that EMGC will serve as a valuable reference data set for future metagenomic studies in mice