Sodium butyrate alleviates cholesterol gallstones by regulating bile acid metabolism.

Abstract

Cholesterol overloading and bile acid metabolic disorders play an important role in the onset of cholesterol gallstone (CGS). Short-chain fatty acids (SCFAs) can regulate bile acid metabolism by modulating the gut microbiota. However, the role and mechanism by which sodium butyrate (NaB) targets bile acids to attenuate CGS are still unknown. In this study, continuous administration of 12 mg/day for 8 weeks was decreased the incidence of gallstones induced by lithogenic diet (LD) from 100% to 25%. NaB modulated SCFAs and improved the gut microbiota. The remodeling of the gut microbiota changed the bile acid compositions and decreased cecal tauro-α-muricholic acid (T-α-MCA) and tauro-β-muricholic acid (T-β-MCA) which are effective farnesoid X receptor (FXR) antagonists. The quantitative real-time PCR examination showed that NaB significantly increased levels of ileal Fxr, fibroblast growth factor-15 (Fgf-15) and small heterodimer partner (Shp) mRNA and subsequently inhibited bile acid synthesis. In addition, NaB enhanced bile acid excretion by increasing the levels of hepatic multidrug resistance protein 2 (Mdr2) and bile salt export pump (Bsep) mRNA, and it enhanced bile acid reabsorption in the intestine by increasing the levels of ileal bile acid transporter (Ibat) mRNA. In addition, NaB reduced the absorption of cholesterol in the intestine and inhibited the excretion of cholesterol in the liver, which reduced the cholesterol concentration in serum and bile. Furthermore, the protective effects of NaB administration were abolished by FXR antagonists. Taken together, our results suggest that NaB mitigates CGS by modulating the gut microbiota to regulate the FXR-FGF-15/SHP signaling pathway.

• Authors: Xin Ye, Shuang Shen, Zhengjie Xu, Qian Zhuang, Jingxian Xu, Jingjing Wang, Zhixia Dong, Xinjian Wan
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 908 Pg. 174341 (Oct 05 2021) ISSN: 1879-0712 [Electronic] Netherlands
• PMID: 34273384 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 Elsevier B.V. All rights reserved.

Chemical References

• ABCB11 protein, human
• ATP Binding Cassette Transporter, Subfamily B, Member 11
• Bile Acids and Salts
• Receptors, Cytoplasmic and Nuclear
• nuclear receptor subfamily 0, group B, member 2
• Butyric Acid

Topics

• ATP Binding Cassette Transporter, Subfamily B, Member 11
• Bile Acids and Salts
• Butyric Acid
• Gallstones
• Receptors, Cytoplasmic and Nuclear