A study of Yanjun. et al
Although the benefits of vertical sleeve gastrectomy surgery (VSG) are clear, the molecular mechanisms by which VSG alleviates obesity and its complications remain unclear. In addition to observing increasedthat circulating bile acid (BA) levels are increased after VSG in mice, here we found that the expression of sterol 12α-hydroxylase (CYP8B1), a key enzyme in controlling the ratio of 12α-hydroxylated (12α-OH) BAs to non-12α-OH BAs, is strongly downregulated after VSG. Using genetic mouse models of CYP8B1 overexpression, knockdown, and knockout, we demonstrated that VSG-induced alterations to the enterohepatic BA circulation and BA composition depend on CYP8B1. As a consequence of these alterations, intestinal lipid absorption is restricted and the gut microbiome (GM) is shifted, which contributes to the metabolic effects of VSG. These results suggest that CYP8B1 is a critical downstream target of VSG. Therefore, modulation of BAbile acid composition and GMgut microbiota profile may be a promising strategy for the development of therapies that non-invasively mimic bariatric surgery to treat obesity and its complications.