Probiotics alleviate inflammatory bowel disease in mice by regulating intestinal microorganisms-bile acid-NLRP3 inflammasome pathway

Abstract

The objective of the present study was to elucidate the mechanism of intestinal microorganisms- bile acid- NLRP3 inflammasome regulation in mice with inflammatory bowel disease treated with probiotics. The abnormal activation of NLRP3 inflammasome is the main pathogenic factor that leads to the development of chronic colitis in IL-10–/– mice. In this study, we divided the IL-10–/– and wild-type mice on a C57BL/6 background into 3 groups: control group (wt mice, n=10), IBD group (IL-10–/– mice, n=10), and probiotic group (IL-10–/– mice treated with probiotics, n=10). The analyses included mRNA levels of cytokines and protein expression of NLRP3 inflammasome and NOD2, as well as colorimetric determination of Wnt, Notch and BMP activity in colon tissue and fresh colon mass. The fresh colon mass was increased in the IBD mice when compared with the control and the probiotic groups (P<0.05). The histological score of the proximal colon in the IBD group was higher than in two other groups (P<0.05). The probiotic group showed lower levels of IFN-γ, IL-17F, IL-1α and IL-25 mRNA compared to the IBD group (P<0.05). The main components of NLRP3 inflammasome (NLRP3, ASC, caspase-1 and IL-1β) and NOD2 were increased in IBD group compared to the control, and decreased after probiotic treatment (P<0.05). FXR, TGR5, vitamin D, and CAR were all increased in IBD group compared to the control and probiotic groups (P<0.05). In conclusion, probiotics modulated the intestinal microbial-bile acid-NLRP3 inflammation in IBD mice.