Gut Microbial Species and Endotypes Associate with Remission in Ulcerative Colitis Patients Treated with Anti-TNF or Anti-integrin Therapy.

Abstract

The gut microbiota contributes to aberrant inflammation in inflammatory bowel disease, but the bacterial factors causing or exacerbating inflammation are not fully understood. Further, the predictive or prognostic value of gut microbial biomarkers for remission in response to biologic therapy is unclear. We perform whole metagenomic sequencing of 550 stool samples from 287 ulcerative colitis patients from a large, phase 3, head-to-head study of infliximab and etrolizumab. We identify several bacterial species in baseline and/or post-treatment samples that associate with clinical remission. These include previously described associations [Faecalibacterium prausnitzii_F] as well as new associations with remission to biologic therapy [Flavonifractor plautii]. We build multivariate models and find that gut microbial species are better predictors for remission than clinical variables alone. Finally, we describe patient groups that differ in microbiome composition and remission rate after induction therapy, suggesting the potential utility of microbiome-based endotyping. In this large study of ulcerative colitis patients, we show that few individual species associate strongly with clinical remission, but multivariate models including microbiome can predict clinical remission and have better predictive power compared with clinical data alone.