High Bile Acid-induced by High-fat Diet Impairs Intestinal Mucosa by Down-regulating Stem Cell Function / 胃肠病学

ABSTRACT

Background:High-fat diet leads to intestinal mucosa barrier dysfunction,but the mechanism is not clear. High-fat diet can induce increase of bile acid. Aims:To investigate whether the high bile acid induced by high-fat diet could act on intestinal stem cell to disrupt stem cell differentiation and imparing the intestinal mucosa. Methods:Twenty-four rats were divided into 3 groupsfed with regular diet,high-fat diet and high-fat diet + cholestyramine,respectively,for 2 weeks. Serum bile acid was detected by ELISA. Ileal diameter was measured and HE staining was performed to observe histology of intestinal mucosa. Expression of Lgr5 gene was determined by RT-qPCR. Ileal tissue fed with regular diet was cultured with deoxycholic acid(DCA)or DCA + cholestyramine for 24 hours in vitro,expression of Lgr5 gene was determined by RT-qPCR. Results:Compared with control group,serum bile acid was significantly increased(P < 0. 05),ileal diameter was significantly decreased,height of intestinal crypts and villus was significantly decreased(P < 0. 05),and expression of Lgr5 gene was significantly decreased in high-fat diet group(P < 0. 01). All the above-mentioned indices were significantly ameliorated in high-fat diet + cholestyramine group(P < 0. 05). In vitro study showed that expression of Lgr5 gene was significantly decreased in DCA group than in control group(P < 0. 01),and cholestyramine could significantly increase expression of Lgr5 gene(P < 0. 05). Conclusions:High-fat diet induced increasing of circulatory bile acid can cause injury of intestinal mucosa by inhibiting stem cell function,which can be ameliorated by cholestyramine.