Enterobacter ludwigii protects DSS-induced colitis through choline-mediated immune tolerance

Commensal intestinal bacteria play key roles in regulating cells mediating immune tolerance; however, bacterial strains and related metabolites directly involved in this regulation are largely unknown. Here, using a mouse model of dextran sulfate sodium (DSS)-induced colitis combined with different antibiotic treatment, Enterobacter ludwigii, abundant in microbiota of mice treated with metronidazole, was screened out to have prophylactic and therapeutic effects on DSS-induced colitis with or without the presence of complex intestinal bacteria. E. ludwigii was demonstrated to induce CD103+DC and Treg-mediated immune tolerance for colitis remission using in vitro and in vivo experiments. Moreover, choline, one of E. ludwigii metabolites, was identified to increase DCs’ immune tolerance to promote Treg differentiation. E. ludwigii was found to induce DCs’ immune tolerance ability for Treg differentiation through choline and α7nAChR-mediated RA and TGF-β upregulation, resulting in protecting mice against DSS-induced colitis. This study provides potential therapeutic approaches for IBD.