Probiotic Combination of HF07 and HF08 Targeting Gut Microbiota-Secondary Bile Acid Metabolism Ameliorates Inflammation and Intestinal Barrier Dysfunction in Aging Colitis.

This study investigated the intestinal protective effects of a probiotic mixture (PM) composed of HF07 and HF08 on d-gal/DSS-induced aging colitis in mice. The PM alleviated age-related colitis symptoms including weight loss, increased disease activity index scores, colonic shortening, and tissue damage. PM supplementation reshaped the gut microbiota by restoring the relative abundances of , , , and -014, thereby enhancing levels of bile acids (BAs) such as alpha-muricholic acid, isolithocholic acid, and ursodeoxycholic acid. Moreover, transcriptomic analysis revealed that PM administration activated the cAMP pathway through the gut microbiota-secondary BAs axis. Western blot analysis further demonstrated that the effects of anti-inflammatory and intestinal barrier repair induced by PM were associated with downregulation of key proteins in the NLRP3 and RhoA/ROCK pathways, both of which are downstream of the cAMP pathway. Additionally, the role of gut metabolites in mediating these effects via G protein-coupled receptor 5 (TGR5) activation was confirmed through in vitro experiments using Caco-2 cells. These findings provided a comprehensive understanding of how probiotics target intestinal metabolites and leverage the gut microbiota-BAs axis to mitigate age-related gastrointestinal diseases.