Clonorchis sinensis Infection prevents DSS-induced Colitis Via Lithocholic Acid in a Gut Microbiota-Dependent Manner.

Abstract

Increasing evidence demonstrates that helminth and its components can ameliorate ulcerative colitis. Clonorchis sinensis (C. sinensis) is a kind of helminth that dwells in the bile ducts for many years, but the roles and underlying mechanisms of C. sinensis-induced protection from colitis are not elucidated. In the present study, the mice were infected with 50 C. sinensis metacercariae and further administrated with 4% Dextran Sodium Sulfate (DSS) in drinking water for 7 days on days 49 post-infection. The disease severity and the integrity of gut barriers were evaluated. Gut microbiota was measured using 16sRNA sequencing, and bile acids in the colon were detected by Liquid Chromatography Mass Spectrometry (LC/MS). The Co-housing approach or microbiota deletion with additional supplies of secondary bile acids (SBAs) was employed to investigate the roles of gut microbiota in the protection from colitis. C. sinensis infection moderated the dysbiosis of the intestinal microbiota and increased the levels of SBAs and bile acid receptor Takeda G protein-coupled receptor 5 (TGR5), which finally benefited anti-inflammation and ameliorated the severity of DSS-induced colitis. Co-housing with C. sinensis-infected mice, and non-infected mice with colitis also showed an increase of TGR5, decreased pro-inflammatory cytokines, and a reduction in the severity of colitis, compared to those mice suffering from colitis without co-housing. Furthermore, C. sinensis-induced protective effects on colitis were attenuated by microbiota deletion, while SBAs (lithocholic acid, LCA) supplementation reversed the colitis. The present study demonstrates that C. sinensis infection ameliorates DSS-induced ulcerative colitis in mice, which is dependent on gut microbiota-associated SBAs.