Bacteroides uniformis regulates TH17 cell differentiation and alleviates chronic colitis by producing alpha-muricholic acid

Abstract Inflammatory bowel disease (IBD) cause colitis-associated malignancy. Studies have shown that IBD development is associated with dysbiosis of the gut microbiota using the IBD model of animals and humans. Bacteroides uniformis , the most abundant core strain in mammals, regulates animal intestinal homoeostasis. However, the key metabolic compounds and mechanism by which B. uniformis treats colitis in mice are unknown. In this study, B. uniformis JCM5828-gavaged female C57BL/6 mice (n = 8) greatly alleviated the progression of DSS-induced colitis and restored the expression of mechanical and immune barrier proteins in the colon. Furthermore, increased abundance of B. uniformis in the colon promoted the abundance of the symbiotic bacteria Bifidobacterium and Lactobacillus vaginalis and inhibited the ecological niche of pathogenic Escherichia coli , thus regulating intestinal lipid metabolism function. Specifically, B. uniformis significantly increased the synthesis of primary and secondary bile acids (alpha-Muricholic acid (α-MCA), Isochenodeoxycholic acid (isoCDCA), hyodeoxycholic acid (HDCA), and isolithocholic acid (isoLCA)) in the colonic contents. B. uniformis also significantly regulated the expression of key regulator genes and proteins of the NF-κB and MAPK signaling pathways in colonic tissues and inhibited TH17 differentiation. In vitro cellular validation showed that single B. uniformis could not significantly inhibit TH17 differentiation in T lymphocytes. In contrast, key metabolic molecules α-MCA, HDCA and isoLCA could inhibit TH17 differentiation in the lamina propria and regulate the intestinal immune response. Cumulatively, the results indicate that B. uniformis JCM5828 supplementation may be an optional approach to the treat colitis and other diseases associated with intestinal barrier dysfunction.