Qifan Lu1, Zhaoyan Jiang2, Qihan Wang2, Hai Hu2, Gang Zhao3. 1. Tongji University School of Medicine, Shanghai 200092, China. 2. Cholelithiasis Center, Tongji University Affiliated Shanghai East Hospital, Shanghai 200120, China. 3. Cholelithiasis Center, Tongji University Affiliated Shanghai East Hospital, Shanghai 200120, China. Electronic address: zhao_gang@126.com.
Abstract
INTRODUCTION AND OBJECTIVES: The incidence of gallstone-related disease steadily increased in the last few years. Here, we aimed to investigate the effect of tauroursodeoxycholic acid1 (TUDCA) on preventing cholesterol gallstones formation in high-fat fed (HFD) mice. MATERIAL AND METHODS: Specific pathogen-free male C57Bl/6 mice were fed a lithogenic diet2 (LD group) alone or in combination with TUDCA (5g/kg diet) for 8 weeks. Upon sacrifice, serum, gallbladder, liver and small intestine were collected and the formation of gallstones or crystals in the gallbladder was analyzed. Additionally, the intestinal microbiota, and bile acid composition, serum lipids and hepatic lipids were studied. RESULTS: Cholesterol gallstones with cholesterol crystals formed in mice of the LD-fed group (15/15, 100%). However, only cholesterol crystals were found in three mice without the presence of any gallstone in the TUDCA-treated group. Both serum and hepatic total cholesterol levels in the TUDCA group were significantly decreased compared with the LD group. Concomitantly, mRNA expression of Abcg5 and Abcg8 was significantly lower in the liver of the TUDCA group whilst mRNA transcripts for Abcb11, Acat2, and Cyp27 were significantly increased compared with the LD group. Additionally, the gallbladder cholesterol saturation index (1.06±0.15) in the TUDCA group was significantly decreased compared with the LD group. Interestingly, the ratio of Firmicutes/Bacteroides in the TUDCA group was increased 3x fold. CONCLUSIONS: TUDCA can inhibit the absorption and synthesis of lipids in the small intestine by improving the intestinal microbiota in HFD-fed mice, thus reducing gallstone formation.
INTRODUCTION AND OBJECTIVES: The incidence of gallstone-related disease steadily increased in the last few years. Here, we aimed to investigate the effect of tauroursodeoxycholic acid1 (TUDCA) on preventing cholesterol gallstones formation in high-fat fed (HFD) mice. MATERIAL AND METHODS: Specific pathogen-free male C57Bl/6 mice were fed a lithogenic diet2 (LD group) alone or in combination with TUDCA (5g/kg diet) for 8 weeks. Upon sacrifice, serum, gallbladder, liver and small intestine were collected and the formation of gallstones or crystals in the gallbladder was analyzed. Additionally, the intestinal microbiota, and bile acid composition, serum lipids and hepatic lipids were studied. RESULTS: Cholesterol gallstones with cholesterol crystals formed in mice of the LD-fed group (15/15, 100%). However, only cholesterol crystals were found in three mice without the presence of any gallstone in the TUDCA-treated group. Both serum and hepatic total cholesterol levels in the TUDCA group were significantly decreased compared with the LD group. Concomitantly, mRNA expression of Abcg5 and Abcg8 was significantly lower in the liver of the TUDCA group whilst mRNA transcripts for Abcb11, Acat2, and Cyp27 were significantly increased compared with the LD group. Additionally, the gallbladder cholesterol saturation index (1.06±0.15) in the TUDCA group was significantly decreased compared with the LD group. Interestingly, the ratio of Firmicutes/Bacteroides in the TUDCA group was increased 3x fold. CONCLUSIONS: TUDCA can inhibit the absorption and synthesis of lipids in the small intestine by improving the intestinal microbiota in HFD-fed mice, thus reducing gallstone formation.
Authors: Thomas C A Hitch; Lindsay J Hall; Sarah Kate Walsh; Gabriel E Leventhal; Emma Slack; Tomas de Wouters; Jens Walter; Thomas Clavel Journal: Mucosal Immunol Date: 2022-09-30 Impact factor: 8.701
Authors: Allie E Steinberger; Maria E Tecos; Hannah M Phelps; Deborah C Rubin; Nicholas O Davidson; Jun Guo; Brad W Warner Journal: Am J Physiol Gastrointest Liver Physiol Date: 2022-06-21 Impact factor: 4.871