Sequencing the cecal microbiota of FXR-/- and WT mice after vertical sleeve gastrectomy (VSG) and sham operations

Vertical sleeve gastrectomy (VSG) is an effective therapy for the treatment of obesity and for the improvement of co-morbidities, including type-2 diabetes mellitus. The underlying molecular mechanisms contributing to these benefits remain undetermined, but changes in circulating total bile acids occur after VSG. Bile acids are known to regulate metabolism by binding to the nuclear receptor FXR (farsenoid-X receptor, also known as NR1H4). We therefore examined the results of VSG surgery applied to mice with diet-induced obesity and targeted genetic disruption of FXR. We demonstrate that VSG is associated with increased circulating bile acid, and changes to gut microbial communities. We observed that that VSG had a stronger effect on microbiota composition in WT mice than in KO mice. Additionally, the relative abundance of several bacteria previously identified as important modulators of systemic metabolism was altered differently by VSG in WT and FXR-/- mice. Moreover, in the absence of FXR, the ability of VSG to reduce body weight and improve glucose tolerance is reduced. These results point to bile acids and FXR signalling as an important molecular underpinning for the beneficial effects of this weight-loss surgery.