2. Academic Validation
  3. Sodium butyrate alleviates cholesterol gallstones by regulating bile acid metabolism

Sodium butyrate alleviates cholesterol gallstones by regulating bile acid metabolism

  • Eur J Pharmacol. 2021 Oct 5;908:174341. doi: 10.1016/j.ejphar.2021.174341.
Xin Ye 1,  Shuang Shen 2,  Zhengjie Xu 3,  Qian Zhuang 1,  Jingxian Xu 4,  Jingjing Wang 4,  Zhixia Dong 5,  Xinjian Wan 6
Affiliations

Affiliations

  • 1 Shanghai Jiao Tong University Affiliated Sixth People's Hospital, School of Medicine, Shanghai, China; Digestive Endoscopic Center, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, China.
  • 2 Shanghai Jiao Tong University Affiliated Sixth People's Hospital, School of Medicine, Shanghai, China.
  • 3 Department of Gastroenterology, Xinhua Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, China.
  • 4 Shanghai Key Laboratory of Pancreatic Disease, Institute of Pancreatic Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 5 Shanghai Jiao Tong University Affiliated Sixth People's Hospital, School of Medicine, Shanghai, China; Digestive Endoscopic Center, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, China. Electronic address: dzhixia2013@163.com.
  • 6 Shanghai Jiao Tong University Affiliated Sixth People's Hospital, School of Medicine, Shanghai, China; Digestive Endoscopic Center, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, China. Electronic address: slwanxinjian2020@126.com.
PMID: 34273384 DOI: 10.1016/j.ejphar.2021.174341
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.

Keywords

Bile acid; Cholesterol gallstone; Farnesoid X receptor; Short-chain fatty acids; Sodium butyrate.

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