Gut Microbiota Facilitates the Preventive Effects of Barley Leaf Against Colitis by Improving Pparγ-Mediated Mucosal Barrier Function

Abstract

Background: Dietary changes associated with westernization have resulted in an increased prevalence of many chronic inflammatory diseases such as inflammatory bowel disease (IBD). Barley leaf (BL) has a long history of use in traditional Chinese medicine with potential health-promoting properties, while its beneficial effects on IBD prevention have not been examined. Methods: By using 16S rDNA gene-based microbiota analysis, electronic microscopy, and RNA sequencing, we examined the mechanisms underlying the preventive effects of BL on colonic inflammation in a dextran sulfate sodium (DSS)-induced colitis mouse model. Findings: BL alleviated DSS-induced colitis severity, as evidenced by reduced body weight loss, disease activity index, and colon shortening. This was companied by inhibited expansion of Enterobacteriaceae in the colonic contents of DSS-treated mice. Furthermore, the beneficial effects of BL against colitis were largely due to its preventive activities before DSS induction. The gut microbiota contributed to the beneficial effects of BL since transfer of BL-cultured fecal microbiota protected against DSS-induced colitis and mucosal barrier damage. Mechanically, BL caused mucus hyperproduction in colonic goblet cells, which was significantly inhibited by treatment with the peroxisome proliferator-activated receptor (PPAR)γ antagonist GW9662. Antibiotic treatment revealed that the effects of BL on mucus hyperproduction and DSS-induced colitis was lost in the absence of gut microbiota. Interpretation: Our results showed that BL protected against DSS-induced colitis by promoting PPARγ-mediated mucus hyperproduction, a mechanism that relied on regulation of the gut microbiota. Funding: This work was supported by Beijing Municipal Science and Technology Project Fund [No. D161100005416001] and Chinese Universities Scientific Fund [No. 2016SP003]. Declaration of Interest: The authors declare no conflict of interest. Ethical Approval: The mouse experiments were performed in accordance with the guidelines of the local ethics committee.