Bile acid 7a-dehydroxylating bacteria accelerate injury-induced mucosal healing in the colon

Host-microbiome communication is frequently perturbed in gut pathologies due to microbiome dysbiosis, leading to altered production of bacterial metabolites. Among these, 7a-dehydroxylated bile acids are notably diminished in inflammatory bowel disease patients. Herein, we investigated whether restoration of 7a-dehydroxylated bile acids levels by Clostridium scindens, a human-derived 7a-dehydroxylating bacterium, can reestablish intestinal epithelium homeostasis following colon injury. Gnotobiotic and conventional mice were subjected to chemically-induced experimental colitis following administration of Clostridium scindens. Colonization enhanced the production of 7a-dehydroxylated bile acids and conferred prophylactic and therapeutic protection against colon injury through epithelial regeneration and specification. Computational analysis of human datasets confirmed defects in intestinal cell renewal and differentiation in ulcerative colitis patients while expression of genes involved in those pathways showed a robust positive correlation with 7a-dehydroxylated bile acid levels. Clostridium scindens administration could therefore be a promising biotherapeutic strategy to foster mucosal healing following colon injury by restoring bile acid homeostasis. Overall design: BRB-seq profiling of colon from 10-week-old male wild-type (Tgr5+/+) and TGR5 knock-out (Tgr5-/-) mice were gavaged daily for 5 days with live C. scindens after 7 days of vancomycin treatment (500mg/l in drinking water) (108 CFU – Tgr5+/+ SPF-Van + C. scindens and Tgr5-/- SPF-Van + C. scindens) or vehicle (PBS - Tgr5+/+ SPF-Van and Tgr5-/- SPF-Van). Experimental colitis was induced by a 7-day treatment with DSS (2.5% in drinking water) followed by 3 days of drinking water (recovery period).