Bacteriology
Effects of cholesterol-lowering probiotics on the metabolism of bile acid in a rat model of non-alcoholic fatty liver disease and the possible mechanism
Limei Bai, Pengyuan Zheng, Jun Zhang, Fuguang Li, Lu Mei, Huang Huang, Yirui Ding, Simeng Liu
Published 2016-02-29
Cite as Chin J Microbiol Immunol, 2016, 36(2): 110-116. DOI: 10.3760/cma.j.issn.0254-5101.2016.02.006
Abstract
ObjectiveTo investigate the effects of two cholesterol-lowering probiotics, DM9054 (Lactobacillus Rhamnosus GG, LGG) in combination with 86066 (Lactobacillus plantarum WCFS1, LP), on the metabolism of bile acid via a rat model of non-alcoholic fatty liver disease (NAFLD) and the possible mechanism.
MethodsTwenty-one SD male rats were randomly divided into three groups including control group, NAFLD model group and probiotics intervention group. Rats in the control group received normal diet. The rat model of NAFLD was established by feeding rats with chronic high fat diet (45% of calories derived from fat diet) for 20 weeks. Rats in the probiotics intervention group were given high fat diet together with cholesterol-lowering probiotics through oral gavage. General indexes of each group including body weight and the levels of triglyceride, cholesterol and CK18-M30 in serums samples were detected. The expression of cholesterol 7-alpha hydroxy-lase (CYP7A1), fibroblast growth factor receptor 4 (FGFR4), farnesoid X receptor (FXR), fibroblast grwoth factor 15 (FGF15) and apical sodium-dependent bile acid transparter(ASBT) at mRNA level were detected by using real-time polymerase chain reaction (real-time PCR). Western blot assay was used to detect the protein expression of CYP7A1, FXR in liver tissues and ASBT in ileum tissues. The expression of FXR in liver and ileum tissues were analyzed by immunohistochemistry.
ResultsRats with NAFLD showed loss of body weight and decreased levels of the serological markers after treating with the probiotics (P<0.05). Compared with the rats in model group, enhanced expression of CYP7A1 and inhibited expression of FXR in liver tissues, activated FXR-FGF15 pathway in ileum tissues as well as down-regulated expression of ASBT in ileum tissues were detected in rats receiving probiotics intervention (P<0.05). No significant difference in the expression of FGFR4 at mRNA level was observed between NAFLD rats with or without probiotics intervention (P>0.05).
ConclusionProbiotics intervention might up-regulate the expression of CYP7A1 by suppressing the FXR pathway in liver tissues and inhibiting the expression of ASBT in ileum tissues. Treating NAFLD rats with cholesterol-lowering probiotics could activate the FXR-FGF15 pathway in ileum tissues and enhance the metabolism of bile acid, which contributed to the alleviation of NAFLD.
Key words:
Non-alcoholic fatty liver disease; Probiotics; Cholesterol 7-alpha hydroxy-lase; Farnesoid X receptor
Contributor Information
Limei Bai
Department of Gastroenterology, the Second Affiliated Hospital of Zhengzhou University, Zhengzhou 450014, China
Pengyuan Zheng
Department of Gastroenterology, the Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
Jun Zhang
Department of Pharmacy, the Second Affiliated Hospital of Zhengzhou University, Zhengzhou 450014, China
Fuguang Li
Department of Microbiology and Immunology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, China
Lu Mei
Department of Gastroenterology, the Second Affiliated Hospital of Zhengzhou University, Zhengzhou 450014, China
Huang Huang
Department of Gastroenterology, the Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
Yirui Ding
Department of Gastroenterology, the Second Affiliated Hospital of Zhengzhou University, Zhengzhou 450014, China
Simeng Liu
Department of Gastroenterology, the Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
