Increasing the Hindgut Carbohydrate/Protein Ratio by Cecal Infusion of Corn Starch or Casein Hydrolysate Drives Gut Microbiota-Related Bile Acid Metabolism To Stimulate Colonic Barrier Function
Yu Pi, Chunlong Mu, Kan Gao, Zhuang Liu, Yu Peng, Weiyun Zhu
Abstract
High-fiber or high-protein diets could alter gut microbiota and health in the large intestine, but factors involved in the effects remain unclear. The present study for the first time demonstrates that the starch- and casein-induced C/N ratio in the hindgut is an important factor. Using the cannulated pig model, we found that the distinct C/N ratio induced by cecal infusion of corn starch or casein hydrolysate was linearly correlated with microbial metabolites (secondary bile acids) and tight junction proteins (ZO-1 and OCLD). Cell culture study further demonstrates that the gut microbial metabolites (DCA and LCA) could impair the intestinal barrier function via the EGFR-Src pathway. These suggest that DCA and LCA were key metabolites mediating microbe-epithelium dialogue when the hindgut C/N ratios were altered by cecal infusion of corn starch or casein hydrolysate. These findings provide new insight into the impact of C/N ratio in the large intestine on colonic health and provide a new framework for therapeutic strategy in gut health through targeted manipulation of hindgut microbiota by increasing the carbohydrate level in the large intestine.