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A novel Ruminococcus gnavus clade enriched in inflammatory bowel disease patients

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TLDR
In this article, the authors performed metagenomic sequencing of monthly stool samples from 20 IBD patients and 12 controls (266 total samples) and identified strain-specific functional correlates with IBD outcomes.
Abstract
Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the gastrointestinal tract that is associated with changes in the gut microbiome. Here, we sought to identify strain-specific functional correlates with IBD outcomes. We performed metagenomic sequencing of monthly stool samples from 20 IBD patients and 12 controls (266 total samples). These were taxonomically profiled with MetaPhlAn2 and functionally profiled using HUMAnN2. Differentially abundant species were identified using MaAsLin and strain-specific pangenome haplotypes were analyzed using PanPhlAn. We found a significantly higher abundance in patients of facultative anaerobes that can tolerate the increased oxidative stress of the IBD gut. We also detected dramatic, yet transient, blooms of Ruminococcus gnavus in IBD patients, often co-occurring with increased disease activity. We identified two distinct clades of R. gnavus strains, one of which is enriched in IBD patients. To study functional differences between these two clades, we augmented the R. gnavus pangenome by sequencing nine isolates from IBD patients. We identified 199 IBD-specific, strain-specific genes involved in oxidative stress responses, adhesion, iron-acquisition, and mucus utilization, potentially conferring an adaptive advantage for this R. gnavus clade in the IBD gut. This study adds further evidence to the hypothesis that increased oxidative stress may be a major factor shaping the dysbiosis of the microbiome observed in IBD and suggests that R. gnavus may be an important member of the altered gut community in IBD.

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Journal ArticleDOI

Multi-omics of the gut microbial ecosystem in inflammatory bowel diseases.

TL;DR: It is demonstrated that periods of disease activity were also marked by increases in temporal variability, with characteristic taxonomic, functional, and biochemical shifts, and integrative analysis identified microbial, biochemical, and host factors central to this dysregulation.
Journal ArticleDOI

Role of gut microbiota in type 2 diabetes pathophysiology.

TL;DR: Evidence from 42 human studies reporting microbial associations with disease, and supporting preclinical studies or clinical trials using treatments with probiotics are identified, found the genera of Bifidobacterium, Bacteroides, Faecalibacteriaium, Akkermansia and Roseburia were negatively associated with T2D, while theGenera of Ruminococcus, Fusobacteria, and Blautia were positively associated withT2D.
Journal ArticleDOI

Gut microbiota-derived metabolites as key actors in inflammatory bowel disease.

TL;DR: This Review aims to define the key classes of microbial-derived metabolites that are altered in IBD, describe the pathophysiological basis of these associations and identify future targets for precision therapeutic modulation.
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The Integrative Human Microbiome Project

TL;DR: Over ten years, the Human Microbiome Project has provided resources for studying the microbiome and its relationship to disease; this Perspective summarizes the key achievements and findings of the project and its relation to the broader field.
References
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Journal ArticleDOI

Structure, function and diversity of the healthy human microbiome

Curtis Huttenhower, +253 more
- 14 Jun 2012 - 
TL;DR: The Human Microbiome Project Consortium reported the first results of their analysis of microbial communities from distinct, clinically relevant body habitats in a human cohort; the insights into the microbial communities of a healthy population lay foundations for future exploration of the epidemiology, ecology and translational applications of the human microbiome as discussed by the authors.
Journal Article

Structure, function and diversity of the healthy human microbiome

Curtis Huttenhower, +247 more
- 01 Jun 2012 - 
TL;DR: The Human Microbiome Project has analysed the largest cohort and set of distinct, clinically relevant body habitats so far, finding the diversity and abundance of each habitat’s signature microbes to vary widely even among healthy subjects, with strong niche specialization both within and among individuals.
Journal ArticleDOI

Genetics and pathogenesis of inflammatory bowel disease

TL;DR: Recent advances have provided substantial insight into the maintenance of mucosal immunity and the pathogenesis of inflammatory bowel disease, and the role of genetic predispositions and how they affect interactions with microbial and environmental factors is emphasized.
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