Understanding the role of ursodeoxycholic acid and gut microbiome in non-alcoholic fatty liver disease: current evidence and perspectives

Qingyi Mao; Beibei Lin; Wenluo Zhang; Yu Zhang; Yu Zhang; Qian Cao; Mengque Xu

doi:10.3389/fphar.2024.1371574

Understanding the role of ursodeoxycholic acid and gut microbiome in non-alcoholic fatty liver disease: current evidence and perspectives

Front Pharmacol. 2024 Mar 21:15:1371574. doi: 10.3389/fphar.2024.1371574. eCollection 2024.

Authors

Qingyi Mao^#^{1

2}, Beibei Lin^#^{1

2}, Wenluo Zhang^{1

2}, Yu Zhang^{1

2}, Yu Zhang^{1

2

3}, Qian Cao^{1

2

3}, Mengque Xu^{1

2

3}

Affiliations

¹ Department of Gastroenterology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
² Inflammatory Bowel Disease Center, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
³ Institute of Gastroenterology, Zhejiang University, Hangzhou, China.

^# Contributed equally.

Abstract

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, resulting in a huge medical burden worldwide. Accumulating evidence suggests that the gut microbiome and bile acids play pivotal roles during the development of NAFLD. Patients with NAFLD exhibit unique signatures of the intestinal microbiome marked by the priority of Gram-negative bacteria, decreased ratio of Firmicutes/Bacteroidetes (F/B), and increased Prevotella and Lachnospiraceae. The intestinal microbiota is involved in the metabolism of bile acids. Ursodeoxycholic acid (UDCA) is a key determinant in maintaining the dynamic communication between the host and gut microbiota. It generally shows surprising therapeutic potential in NAFLD with several mechanisms, such as improving cellular autophagy, apoptosis, and mitochondrial functions. This action is based on its direct or indirect effect, targeting the farnesoid X receptor (FXR) and various other nuclear receptors. This review aims to discuss the current studies on the involvement of the microbiome-UDCA interface in NAFLD therapy and provide prospective insights into future preventative and therapeutic approaches for NAFLD.

Keywords: bile acid receptors; bile acid–gut microbiome axis; gut microbiome; non-alcoholic fatty liver disease; ursodeoxycholic acid.

Publication types

Review

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the Medical Health Technology Project of Zhejiang, China under grant no. 2021KY749, 2023KY804, and 2024ZL101 to MX) and the Natural Science Foundation of Zhejiang, China under grant LQ21H030010 to YZ (5th author) and LY24H030002 to MX. All authors are indebted to the Medical Health Technology Project of Zhejiang, China and Natural Science Foundation of Zhejiang, China for secretarial support.