Bile Acid Composition Contributes to Metabolic Improvements after Sleeve Gastrectomy in Mice

Abstract

Obesity and type 2 diabetes (T2D) can be managed by vertical sleeve gastrectomy (VSG), one of the most frequently performed bariatric surgeries. Although VSG can effectively reverse obesity and T2D, the underlying mechanism of how VSG does so is still under investigation. We found that VSG altered bile acid (BA) levels and composition in mice, resulting in gut microbiota change and concomitant metabolic improvements. CYP8B1 is a BA synthesis enzyme in the liver. We found that CYP8B1 was significantly downregulated in mice after VSG. To investigate whether or not CYP8B1 mediates the metabolic effects of VSG, we used Cyp8b1‐deficient mouse model. The results show that although VSG induced weight loss and improvement in glucose tolerance in wildtype mice, VSG barely improved the same parameters in Cyp8b1‐deficient mice. Our study indicates that alterations of BA and microbiota compositions contributes to metabolic improvements after sleeve gastrectomy in mice. CYP8B1 could be one of the mediators downstream of VSG. These results provide novel insight into the roles of bile acids and gut microbiota in VSG, and may help develop gut microbiota‐based therapeutic options to mimic VSG.Support or Funding InformationInternal funding