A novel Ruminococcus gnavus clade enriched in inflammatory bowel disease patients

Andrew Brantley Hall, Moran Yassour, Jenny Sauk, Ashley Garner, Xiaofang Jiang, Timothy Arthur, Georgia K. Lagoudas, Tommi Vatanen, Nadine Fornelos, Robin Wilson, Madeline Bertha, Melissa Cohen, John Garber, Hamed Khalili, Dirk Gevers, Ashwin N. Ananthakrishnan, Subra Kugathasan, Eric S. Lander, Paul Blainey, Hera VlamakisRamnik J. Xavier*, Curtis Huttenhower

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

395 Scopus citations

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.

Original languageAmerican English
Article number103
JournalGenome Medicine
Volume9
Issue number1
DOIs
StatePublished - 28 Nov 2017
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2017 The Author(s).

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