Bile Acid Derivatives Effectively Prevented High-Fat Diet-Induced Colonic Barrier Dysfunction

Area of Science:

• Gastroenterology
• Microbiology
• Metabolism

Background:

• Bile acids (BAs) are key regulators of physiological and pathological processes.
• The impact of high-fat diets (HFDs) on colonic BAs and barrier function requires further investigation.

Purpose of the Study:

• To elucidate the changes in colonic bile acids induced by HFDs.
• To investigate the effects of these altered bile acids on colonic barrier function.

Main Methods:

• Mice were fed HFDs for 12 weeks, and intestinal permeability markers (DAO, ET, d-LA) were measured.
• Colonic expression of tight junction proteins (TJs) and Muc2 was analyzed using qPCR and Western blot.
• Colonic BA profiles were determined using UPLC-MS/MS; effects of BAs on Caco-2 cells and HFD-fed mice were assessed.

Main Results:

• HFDs increased intestinal permeability and decreased TJ and Muc2 expression in mice.
• HFDs altered colonic BA profiles, increasing primary BAs and decreasing secondary BAs.
• Secondary BAs, especially isomerized forms (isoDCA, isoLCA), upregulated TJs and counteracted permeability increases in vitro and in vivo.

Conclusions:

• Secondary bile acids, particularly isomerized derivatives, are crucial protectors of colonic barrier function.
• These findings suggest a therapeutic potential for secondary BAs in managing HFD-induced gut barrier dysfunction.