# A bile acid–GPBAR1 network supports anti-inflammatory and anti-fibrotic benefits of probiotics in colitis

## TL;DR

A 9-strain probiotic helps reduce inflammation and fibrosis in chronic colitis by influencing bile acid signaling through GPBAR1.

## Contribution

A new 9-strain probiotic formulation shows anti-inflammatory and anti-fibrotic effects via bile acid-GPBAR1 signaling in chronic colitis.

## Key findings

- The 9-strain probiotic reduces inflammation and fibrosis in chronic colitis but not in acute colitis.
- The probiotic remodels microbiota and increases GPBAR1-agonist bile acids like 3-oxo-DCA.
- The anti-inflammatory effects of the probiotic are lost in mice lacking GPBAR1.

## Abstract

Intestinal fibrosis is a severe complication of Crohn's disease for which therapy remains suboptimal. Probiotics are widely used in the treatment of intestinal inflammation, but all major guidelines do not recommend in favor of their use, with the exception of an 8-strains bacterial formula, which is recommended for the treatment of pouch inflammation in ulcerative colitis. Using this 8-strains formulation as a comparator, we characterized a 9-strains probiotic formulation enriched with Lactobacillus rhamnosus and paracasei in a mouse model of intestinal inflammation and fibrosis. Our findings demonstrated that while both formulations exerted similar protective effects in acute colitis, only the 9-strains probiotic attenuates inflammation and fibrosis in chronic colitis. Mechanistically, we found that the 9-strains formulation remodeled the microbiota composition and the structure of microbiota-derived secondary bile acids, leading to the selective enrichment of those bile acids that act as GPBAR1 agonists, including 3-oxo-DCA, which in vitro directly attenuates activation of intestinal fibroblasts. Confirming the role of this pathway, feeding Gpbar1⁻/⁻ mice with 9-strains probiotic formulation abrogates its beneficial effects on inflammation and fibrosis. These findings highlight the importance of microbial metabolites in shaping probiotic efficacy and support the development of probiotic formulations that target host–microbiota interactions through bile acid signaling.