The effect of Tauroursodeoxycholic acid (TUDCA) and gut microbiota on murine gallbladder stone formation

Nov 20, 2020Annals of hepatology

How Tauroursodeoxycholic Acid and Gut Bacteria Affect Gallbladder Stone Formation in Mice

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Abstract

Cholesterol gallstones formed in 100% of high-fat diet-fed mice, while TUDCA treatment prevented gallstone formation in all treated mice.

Only cholesterol crystals were found in three TUDCA-treated mice, with no gallstones present.
Serum and liver cholesterol levels were significantly lower in the TUDCA group compared to the high-fat diet group.
Gene expression related to cholesterol absorption and synthesis was altered in the TUDCA group, indicating reduced lipid absorption.
The gallbladder cholesterol saturation index was significantly decreased in the TUDCA group.
The ratio of Firmicutes to Bacteroides in the intestinal microbiota increased threefold with TUDCA treatment.

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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 acid(TUDCA) on preventing cholesterol gallstones formation in high-fat fed (HFD) mice. 1

MATERIAL AND METHODS: Specific pathogen-free male C57Bl/6 mice were fed a lithogenic diet(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. 2

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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The effect of Tauroursodeoxycholic acid (TUDCA) and gut microbiota on murine gallbladder stone formation

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