Dataset Information

Extensive Mobilome-Driven Genome Diversification in Mouse Gut-Associated Bacteroides vulgatus mpk.

ABSTRACT: Like many other Bacteroides species, Bacteroides vulgatus strain mpk, a mouse fecal isolate which was shown to promote intestinal homeostasis, utilizes a variety of mobile elements for genome evolution. Based on sequences collected by Pacific Biosciences SMRT sequencing technology, we discuss the challenges of assembling and studying a bacterial genome of high plasticity. Additionally, we conducted comparative genomics comparing this commensal strain with the B. vulgatus type strain ATCC 8482 as well as multiple other Bacteroides and Parabacteroides strains to reveal the most important differences and identify the unique features of B. vulgatus mpk. The genome of B. vulgatus mpk harbors a large and diverse set of mobile element proteins compared with other sequenced Bacteroides strains. We found evidence of a number of different horizontal gene transfer events and a genome landscape that has been extensively altered by different mobilization events. A CRISPR/Cas system could be identified that provides a possible mechanism for preventing the integration of invading external DNA. We propose that the high genome plasticity and the introduced genome instabilities of B. vulgatus mpk arising from the various mobilization events might play an important role not only in its adaptation to the challenging intestinal environment in general, but also in its ability to interact with the gut microbiota.

SUBMITTER: Lange A

PROVIDER: S-EPMC4860699 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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Extensive Mobilome-Driven Genome Diversification in Mouse Gut-Associated Bacteroides vulgatus mpk.

Lange Anna A Beier Sina S Steimle Alex A Autenrieth Ingo B IB Huson Daniel H DH Frick Julia-Stefanie JS

Genome biology and evolution 20160425 4

Like many other Bacteroides species, Bacteroides vulgatus strain mpk, a mouse fecal isolate which was shown to promote intestinal homeostasis, utilizes a variety of mobile elements for genome evolution. Based on sequences collected by Pacific Biosciences SMRT sequencing technology, we discuss the challenges of assembling and studying a bacterial genome of high plasticity. Additionally, we conducted comparative genomics comparing this commensal strain with the B. vulgatus type strain ATCC 8482 as ...[more]

PMID: 27071651

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Project description:Hyperlipidemia is a risk factor and key indicator for cardiovascular diseases, and the gut microbiota is highly associated with hyperlipidemia. Bacteroides vulgatus is a prevalent mutualist across human populations and confers multiple health benefits such as immunoregulation, antiobesity, and coronary artery disease intervention. However, its role in antihyperlipidemia has not been systematically characterized. This study sought to identify the effect of B. vulgatus Bv46 on hyperlipidemia. Hyperlipidemic rats were modeled by feeding them a high-fat diet for 6 weeks. The effect of B. vulgatus Bv46 supplementation was evaluated by measuring anthropometric parameters, lipid and inflammation markers, and the liver pathology. Multi-omics was used to explore the underlying mechanisms. The ability of B. vulgatus Bv46 to produce bile salt hydrolase was confirmed by gene annotation and in vitro experiments. Oral administration of B. vulgatus Bv46 in hyperlipidemic rats significantly reduced the body weight gain, food efficiency, and liver index, improved the serum lipid profile, lowered the levels of serum inflammatory cytokines, promoted the loss of fecal bile acids (BAs), and extended the fecal pool of short-chain fatty acids (SCFAs), especially propionate and butyrate. B. vulgatus Bv46 induced compositional shifts of the gut microbial community of hyperlipidemic rats, characterized by a lower ratio of Firmicutes to Bacteroidetes with an increase of genera Bacteroides and Parabacteroides. After intervention, serum metabolite profiling exhibited an adaptation in amino acids and glycerophospholipid metabolism. Transcriptomics further detected altered biological processes, including primary bile acid biosynthesis and fatty acid metabolic process. Taken together, the findings suggest that B. vulgatus Bv46 could be a promising candidate for interventions against hyperlipidemia. IMPORTANCE As a core microbe of the human gut ecosystem, Bacteroides vulgatus has been linked to multiple aspects of metabolic disorders in a collection of associative studies, which, while indicative, warrants more direct experimental evidence to verify. In this study, we experimentally demonstrated that oral administration of B. vulgatus Bv46 ameliorated the serum lipid profile and systemic inflammation of high-fat diet-induced hyperlipidemic rats in a microbiome-regulated manner, which appears to be associated with changes of bile acid metabolism, short-chain fatty acid biosynthesis, and serum metabolomic profile. This finding supports the causal contribution of B. vulgatus in host metabolism and helps to form the basis of novel therapies for the treatment of hyperlipidemia.

Project description:BackgroundImmune checkpoint blockade (ICB) shows lasting benefits in advanced melanoma; however, not all patients respond to this treatment and many develop potentially life-threatening immune-related adverse events (irAEs). Identifying individuals who will develop irAEs is critical in order to improve the quality of care. Here, we prospectively demonstrate that the gut microbiome predicts irAEs in melanoma patients undergoing ICB.MethodsPre-, during, and post-treatment stool samples were collected from 27 patients with advanced stage melanoma treated with IPI (anti-CTLA-4) and NIVO (anti-PD1) ICB inhibitors at NYU Langone Health. We completed 16S rRNA gene amplicon sequencing, DNA deep shotgun metagenomic, and RNA-seq metatranscriptomic sequencing. The divisive amplicon denoising algorithm (DADA2) was used to process 16S data. Taxonomy for shotgun sequencing data was assigned using MetaPhlAn2, and gene pathways were assigned using HUMAnN 2.0. Compositionally aware differential expression analysis was performed using ANCOM. The Cox-proportional hazard model was used to assess the prospective role of the gut microbiome (GMB) in irAES, with adjustment for age, sex, BMI, immune ICB treatment type, and sequencing batch.ResultsTwo natural GMB clusters with distinct community compositions were identified from the analysis of 16S rRNA data (R2 = 0.16, p < 0.001). In Cox-proportional hazard modeling, these two clusters showed a near 7-fold differential risk for developing irAEs within 1 year of initiating treatment (HR = 6.89 [95% CI: 1.33-35.58]). Using shotgun metagenomics, we further identified 37 bacterial strains differentially expressed between the risk groups, with specific dominance of Bacteroides dorei within the high-risk GMB cluster and Bacteroides vulgatus in the low-risk cluster. The high-risk cluster also appeared to have elevated expression of several functional pathways, including those associated with adenosine metabolism (all FDR < 0.05). A sub-analysis of samples (n = 10 participants) at baseline and 6 and 12 weeks after the start of treatment revealed that the microbiome remained stable over the course of treatment (R2 = 0.88, p < 0.001).ConclusionsWe identified two distinct fecal bacterial community clusters which are associated differentially with irAEs in ICB-treated advanced melanoma patients.

Dataset Information

Extensive Mobilome-Driven Genome Diversification in Mouse Gut-Associated Bacteroides vulgatus mpk.

Publications

Extensive Mobilome-Driven Genome Diversification in Mouse Gut-Associated Bacteroides vulgatus mpk.

Similar Datasets

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