The effect of Tauroursodeoxycholic acid (TUDCA) and gut microbiota on murine gallbladder stone 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 acid11 TUDCA: tauroursodeoxycholic acid (TUDCA) on preventing cholesterol gallstones formation in high-fat fed (HFD) mice...

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Main Authors: Qifan Lu, Zhaoyan Jiang, Qihan Wang, Hai Hu, Gang Zhao
Format: Article
Language:English
Published: Elsevier 2021-07-01
Series:Annals of Hepatology
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S1665268120302143
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author Qifan Lu
Zhaoyan Jiang
Qihan Wang
Hai Hu
Gang Zhao
author_facet Qifan Lu
Zhaoyan Jiang
Qihan Wang
Hai Hu
Gang Zhao
author_sort Qifan Lu
collection DOAJ
description 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 acid11 TUDCA: tauroursodeoxycholic acid (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 diet22 LD: lithogenic diet (LD group) alone or in combination with TUDCA (5 g/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.
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spelling doaj.art-641e6fce769a4b688277d81c80333ff52022-12-21T20:11:44ZengElsevierAnnals of Hepatology1665-26812021-07-0123100289The effect of Tauroursodeoxycholic acid (TUDCA) and gut microbiota on murine gallbladder stone formationQifan Lu0Zhaoyan Jiang1Qihan Wang2Hai Hu3Gang Zhao4Tongji University School of Medicine, Shanghai 200092, ChinaCholelithiasis Center, Tongji University Affiliated Shanghai East Hospital, Shanghai 200120, ChinaCholelithiasis Center, Tongji University Affiliated Shanghai East Hospital, Shanghai 200120, ChinaCholelithiasis Center, Tongji University Affiliated Shanghai East Hospital, Shanghai 200120, China; Corresponding author at: Center of Gallbladder Disease, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 20120, ChinaCholelithiasis Center, Tongji University Affiliated Shanghai East Hospital, Shanghai 200120, China; Corresponding author at: Center of Gallbladder Disease, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 20120, ChinaIntroduction and Objectives: The incidence of gallstone-related disease steadily increased in the last few years. Here, we aimed to investigate the effect of tauroursodeoxycholic acid11 TUDCA: tauroursodeoxycholic acid (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 diet22 LD: lithogenic diet (LD group) alone or in combination with TUDCA (5 g/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.http://www.sciencedirect.com/science/article/pii/S1665268120302143Tauroursodeoxycholic acid (TUDCA)High-fat diet (HFD)Intestinal microbiotaCholesterol stonesLipids
spellingShingle Qifan Lu
Zhaoyan Jiang
Qihan Wang
Hai Hu
Gang Zhao
The effect of Tauroursodeoxycholic acid (TUDCA) and gut microbiota on murine gallbladder stone formation
Annals of Hepatology
Tauroursodeoxycholic acid (TUDCA)
High-fat diet (HFD)
Intestinal microbiota
Cholesterol stones
Lipids
title The effect of Tauroursodeoxycholic acid (TUDCA) and gut microbiota on murine gallbladder stone formation
title_full The effect of Tauroursodeoxycholic acid (TUDCA) and gut microbiota on murine gallbladder stone formation
title_fullStr The effect of Tauroursodeoxycholic acid (TUDCA) and gut microbiota on murine gallbladder stone formation
title_full_unstemmed The effect of Tauroursodeoxycholic acid (TUDCA) and gut microbiota on murine gallbladder stone formation
title_short The effect of Tauroursodeoxycholic acid (TUDCA) and gut microbiota on murine gallbladder stone formation
title_sort effect of tauroursodeoxycholic acid tudca and gut microbiota on murine gallbladder stone formation
topic Tauroursodeoxycholic acid (TUDCA)
High-fat diet (HFD)
Intestinal microbiota
Cholesterol stones
Lipids
url http://www.sciencedirect.com/science/article/pii/S1665268120302143
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