Sea buckthorn berries alleviate ulcerative colitis via regulating gut Faecalibaculum rodentium-mediated butyrate biosynthesis

Abstract

Background

The gut microbiota is firmly associated with the progression of ulcerative colitis (UC). Beneficial microbial metabolites, such as butyrate, exert vital roles in maintaining intestinal homeostasis. The Sea buckthorn berry is a traditional Chinese medicine homologous to food and medicine which is widely applied in the prevention and treatment of UC in clinic practice. Recent studies have exhibited the potential function of Sea buckthorn on regulating the gut microbiota, however, the mechanism underlying its anti-colitis effects and the key gut microbes mediating its efficacy are still unclear.

Purpose

This study is intended to explore the pharmacological mechanism of the efficacy of Sea buckthorn berries extract (SBE) in alleviating UC from the perspective of the gut microbial regulation.

Methods

The effect of SBE on UC was evaluated on dextran sulfate sodium (DSS)-induced murine model by assessing the body weight change, colon length, disease activity index (DAI), histopathological staining and the transcriptional expression of genes associated with inflammation and mucosal integrity. The dependence of the gut microbiota in the therapeutical effects of SBE on UC was confirmed by pseudo-germ-free mice and the co-housing experiment. The differential gut microbes altered by SBE were discovered by 16S rRNA sequencing and qPCR. The levels of short chain fatty acids (SCFAs) in bacterial medium and colonic contents were determined by GC–MS/MS. Bacterial colonization was conducted to estimate the effects of the bacteria on UC and to verify the involvement of the functional bacteria in the efficacy of SBE. A butyrate receptor G protein-coupled receptor (GPR)109A antagonist mepenzolate bromide (MPN) was used to validate the important role of butyrate and GPR109A in the anti-colitis effects of SBE and functional bacteria on UC. Two-way ANOVA was employed for multiple curve comparison and One-way ANOVA and Brown-Forsythe ANOVA test were used for multiple group comparison. Statistical significance was defined as p < 0.05.

Results

SBE treatment significantly alleviated DSS-induced UC and its therapeutical effects was impaired in pseudo-germ-free mice. Moreover, the co-housing experiment exhibited that SBE-altered microbiota could effectively ameliorate UC. Further research demonstrated that Faecalibaculum rodentium was obviously increased by SBE and could be transferable by co-housing. Moreover, butyrate, a product of F. rodentium, dramatically decreased in UC mice while could be recovered by SBE administration. Abolishment of F. rodentium using vancomycin deprived the efficacy of SBE, but this could be reversed by recolonization of F. rodentium. Finally, blockage of the butyrate's receptor GPR109A weakened the effects of F. rodentium, indicating the indispensability of butyrate and GPR109A in the anti-colitis effects of F. rodentium.

Conclusion

SBE has potent therapeutical efficacy on UC including relieving inflammation and enhancing intestinal epithelial integrity, which is mediated by the gut F. rodentium-regulated butyrate−GPR109A axis.