Pathogen-Specific Alterations in the Gut Microbiota Predict Outcomes in Flare of Inflammatory Bowel Disease Complicated by Gastrointestinal Infection

Abstract

INTRODUCTION: Enteric infection with Clostridioides difficile, Escherichia coli subtypes, and norovirus is commonly detected in flares of inflammatory bowel disease (IBD). We associated the gut microbiome during flare complicated by a gastrointestinal pathogen with outcomes of IBD. METHODS: We performed a cross-sectional study of 260 patients (92 IBD and 168 non-IBD) with a gastrointestinal polymerase chain reaction panel positive for C. difficile, E. coli, or norovirus, or negative during an episode of diarrhea from 2018 to 2020, and 25 healthy controls. Clinical variables, IBD status, and 2-year outcomes were collected. Using 16S rRNA sequencing, we measured the effect size of the gut microbiome on IBD characteristics and outcomes. RESULTS: There were major differences in the gut microbiome between patients with and without a pathogen and IBD. In IBD, a higher proportion of patients without a pathogen required hospitalization and IBD therapies at flare and within the 2 years after flare, driven by a milder disease course in flares complicated by an E. coli subtype or norovirus. Examining the contribution of clinical covariates, the presence of IBD, and C-reactive protein, C. difficile had a greater relative influence on the gut microbiome compared with the presence of an E. coli subtype or norovirus. In patients with C. difficile or no pathogen, lower microbiome diversity at flare was associated with adverse IBD outcomes over 2 years. DISCUSSION: Distinctive pathogen-specific gut microbiomes were associated with subsequent IBD outcomes. These findings may have direct implications for the management of IBD flares complicated by enteric pathogens.