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

2026-03-18
Gut microbes 18(1)

PubMed: 41851067
DOI: 10.1080/19490976.2026.2645125

Study Design

Population: mice with intestinal inflammation and fibrosis
Methods: Comparison of 8-strains and 9-strains probiotic formulations in a mouse model of intestinal inflammation and fibrosis; acute and chronic colitis experiments; mechanistic studies of microbiota, bile acids, and GPBAR1 pathway

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.

Research Insights

Supplement	Dose	Health Outcome	Effect Type	Effect Size	Source
Lactobacillus rhamnosus IMC 501	—	Reduced Intestinal Fibrosis	Beneficial	Moderate	View source only the 9-strains probiotic attenuates inflammation and fibrosis in chronic colitis.
Lactobacillus rhamnosus IMC 501	—	Reduced Intestinal Inflammation	Beneficial	Moderate	View source only the 9-strains probiotic attenuates inflammation and fibrosis in chronic colitis.