A novel Ruminococcus gnavus clade enriched in inflammatory bowel disease patients

• Type of Material: Article
• Authors: Andrew Brantley Hall, Broad Institute of MIT and Harvard; Moran Yassour, Broad Institute of MIT and Harvard; Jenny Sauk, Harvard Medical School; Ashley Garner, Broad Institute of MIT and Harvard; Xiaofang Jiang, Broad Institute of MIT and Harvard; Timothy Arthur, Broad Institute of MIT and Harvard; Georgia K. Lagoudas, Broad Institute of MIT and Harvard; Tommi Vatanen, Broad Institute of MIT and Harvard; Nadine Fornelos, Broad Institute of MIT and Harvard; Robin Wilson, Harvard Medical School; Madeline Bertha, Emory University; Melissa Cohen, Harvard Medical School; John Garber, Harvard Medical School; Hamed Khalili, Harvard Medical School; Dirk Gevers, Broad Institute of MIT and Harvard; Ashwin N. Ananthakrishnan, Harvard Medical School; Subramaniam Kugathasan, Emory University; Eric S. Lander, Broad Institute of MIT and Harvard; Paul Blainey, Broad Institute of MIT and Harvard; Hera Vlamakis, Broad Institute of MIT and Harvard; Ramnik J. Xavier, Broad Institute of MIT and Harvard; Curtis Huttenhower, Broad Institute of MIT and Harvard
• Language: English
• Date: 2017-11-28
• Publisher: BioMed Central
• Publication Version: Final Published Version
• Copyright Statement: © 2017 The Author(s).
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1186/s13073-017-0490-5
• Title of Journal or Parent Work: Genome Medicine
• ISSN: 1756-994X
• Volume: 9
• Issue: 1
• Start Page: 103
• End Page: 103
• Grant/Funding Information: M.Y. is supported by NIH NIDDK 1K99DK113224; Klarman Family Foundation; Charles A. King Trust Postdoctoral Fellowship.; C.H. is supported by NSF Grant MCB-1453942.; R.J.X. and C.H. are supported by NIH grant U54DE023798, and the Crohn’s and Colitis Foundation of America.; A.B.H. is a Merck Fellow of the Helen Hay Whitney Foundation.; R.J.X. is supported by NIH grants R01DK92405 and P30DK43351.
• Keywords: DIVERSITY; CLOSTRIDIUM; HUMAN FECES; ULCERATIVE-COLITIS; ANIMAL-MODELS; CROHNS-DISEASE; OXIDATIVE STRESS; RECLASSIFICATION; HUMAN GUT MICROBIOTA; Genetics & Heredity; Science & Technology; COMB. NOV; Life Sciences & Biomedicine
• Research Categories: Biology, General; Health Sciences, General; Biology, Biostatistics

Abstract

Background: 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. Methods: 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. Results: 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. Conclusions: 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.