Impact of strain-level functional diversity in mucin-degrading bacteria on the pathogenesis of inflammatory bowel disease

Objective

Recent advances in microbiome research have revealed numerous associations between gut bacteria and host health. However, these correlations do not establish causality and provide limited insight into the mechanisms by which specific bacteria influence disease. There is therefore a critical need to uncover underlying bacterial functions through targeted studies. This project focuses on inflammatory bowel disease (IBD), a condition marked by chronic intestinal inflammation and disruption of the colonic mucus barrier. Among bacteria linked to IBD are mucin-degraders, which can feed on components of the mucus layer and promote inflammation in gnotobiotic models. One such bacterium, Ruminococcus gnavus, is consistently associated with IBD. Yet its role remains poorly understood, as it is also highly prevalent in the healthy European population (~90%), suggesting that mere presence is not sufficient to drive inflammation. Recent studies and preliminary work from the host lab show that R. gnavus displays substantial genetic and functional diversity across strains, indicating that its pro-inflammatory potential may be strain-dependent and shaped by distinct functional traits. The STRAINGUT project aims to exploit this variability to identify strain-specific functions of R. gnavus that promote inflammation. To this end, a collection of 50 R. gnavus strains will be functionally screened in vitro, followed by in vivo validation of candidate strains in a gnotobiotic model of IBD. This approach will enable the identification of functional markers—which may include specific mucin-degradation processes—that modulate colitis. Their translational relevance will then be assessed using ex vivo human samples and IBD metagenomic datasets. By pinpointing key R. gnavus functions involved in inflammation, STRAINGUT promises to deliver novel mechanistic insights into host–microbiota interactions in IBD and pave the way for innovative strategies to prevent disease in at-risk individuals.