Berberine improves colitis by triggering AhR activation by microbial tryptophan catabolites

Area of Science:

• Gastroenterology
• Microbiology
• Pharmacology

Background:

• Inflammatory bowel diseases (IBD) present complex pathogenesis with unideal clinical treatments.
• Gut barrier dysfunction, driven by gut microbiota dysbiosis, is closely linked to IBD development.

Purpose of the Study:

• To investigate the therapeutic potential of berberine (BBR) in improving dysregulated gut microbiota and ameliorating IBD.
• To elucidate the mechanism by which BBR improves gut barrier function in dextran sulfate sodium (DSS)-induced colitis.

Main Methods:

• Utilized a combination of 16S rDNA amplicon sequencing and targeted metabolomics in a rat model of DSS-induced colitis.
• Employed an in vitro Caco-2 cell monolayer model for mechanistic exploration.

Main Results:

• BBR administration significantly improved pathological phenotypes, gut barrier disruption, and colon inflammation in DSS-induced colitis rats.
• BBR alleviated gut dysbiosis and restored altered microbial tryptophan catabolites.
• Microbial metabolite modulation and aryl hydrocarbon receptor (AhR) activation were identified as key mechanisms for BBR's therapeutic effect on gut barrier disruption.

Conclusions:

• Berberine effectively treats DSS-induced colitis in rats by regulating gut microbiota-associated tryptophan metabolites to activate AhR, thereby improving gut barrier function.
• This study elucidates a novel mechanism for BBR in enhancing gut barrier integrity, offering potential for BBR-based drug discovery for colitis.