|Publication Type||Journal Article|
|Year of Publication||2017|
|Authors||Hall, ABrantley, Yassour, M, Sauk, J, Garner, A, Jiang, X, Arthur, T, Lagoudas, GK, Vatanen, T, Fornelos, N, Wilson, R, Bertha, M, Cohen, M, Garber, J, Khalili, H, Gevers, D, Ananthakrishnan, AN, Kugathasan, S, Lander, ES, Blainey, P, Vlamakis, H, Xavier, RJ, Huttenhower, C|
|Date Published||2017 Nov 28|
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.
|Alternate Journal||Genome Med|
|PubMed Central ID||PMC5704459|
|Grant List||P30 DK043351 / DK / NIDDK NIH HHS / United States |
R01 DK092405 / DK / NIDDK NIH HHS / United States
U54DE023798 / / National Institutes of Health (US) / United States
U54 DE023798 / DE / NIDCR NIH HHS / United States
MCB-1453942 / / National Science Foundation (US) / United States
K99 DK113224 / DK / NIDDK NIH HHS / United States
P30DK43351 / / National Institute of Diabetes and Digestive and Kidney Diseases / United States
R01DK92405 / / National Institute of Diabetes and Digestive and Kidney Diseases / United States