Liuweizhiji Gegen-Sangshen beverage protects against alcoholic liver disease in mice through the gut microbiota mediated SCFAs/GPR43/GLP-1 pathway

Mingyun Tang; Long Zhao; Fuchun Huang; Tiangang Wang; Xu Wu; Shanshan Chen; Juan Fu; Chaoli Jiang; Shulin Wei; Xuseng Zeng; Xiaoling Zhang; Xin Zhou; Mei Wei; Zhi Li; Guohui Xiao

doi:10.3389/fnut.2024.1495695

Liuweizhiji Gegen-Sangshen beverage protects against alcoholic liver disease in mice through the gut microbiota mediated SCFAs/GPR43/GLP-1 pathway

Front Nutr. 2024 Dec 13:11:1495695. doi: 10.3389/fnut.2024.1495695. eCollection 2024.

Authors

Mingyun Tang^#^{1

2}, Long Zhao^#^{1

2}, Fuchun Huang^#^{1

2}, Tiangang Wang^{1

2}, Xu Wu³, Shanshan Chen^{1

2}, Juan Fu^{1

2}, Chaoli Jiang^{1

2}, Shulin Wei^{1

3}, Xuseng Zeng^{1

2}, Xiaoling Zhang^{1

2}, Xin Zhou^{1

2}, Mei Wei⁴, Zhi Li^{1

2

5}, Guohui Xiao^{1

2}

Affiliations

¹ Department of Spleen and Stomach Diseases, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, Sichuan, China.
² The Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Digestive System Diseases of Luzhou City, The Affiliated Traditional Medicine Hospital, Southwest Medical University, Luzhou, Sichuan, China.
³ Cell Therapy and Cell Drugs of Luzhou Key Laboratory, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, China.
⁴ Department of Hepatobiliary Diseases, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, Sichuan, China.
⁵ School of Integrated Traditional Chinese and Western Clinical Medicine, North Sichuan Medical College, Nanchong, Sichuan, China.

^# Contributed equally.

Abstract

Introduction: Alcoholic liver disease (ALD) is a pathological state of the liver caused by longterm alcohol consumption. Recent studies have shown that the modulation of the gut microbiota and its metabolic products, specifically the short-chain fatty acids (SCFAs), exert a critical role in the evolution and progression of ALD. The Liuweizhiji Gegen-Sangshen beverage (LGS), as a functional beverage in China, is derived from a traditional Chinese herbal formula and has been clinically applied for ALD treatment, demonstrating significant efficacy. However, the underlying mechanisms of LGS for alleviating ALD involving gut microbiota regulation remain unknown.

Methods: In this study, an ALD murine model based on the National Institute on Alcohol Abuse and Alcoholism (NIAAA) method was established.

Results: The results showed that oral LGS treatment dose-dependently alleviated alcoholinduced liver injury and inflammation in mice through decreasing levels of ALT, AST and proinflammatory cytokines (TNF-α, IL-6, IL-1β). LGS significantly improved liver steatosis, enhanced activities of alcohol metabolizing enzymes (ALDH and ADH), and reduced the CYP2E1 activity. Notably, regarding most detected indices, the effect of LGS (particularly at medium and high dose) was comparable to the positive drug MTDX. Moreover, LGS had a favorable effect on maintaining intestinal barrier function through reducing epithelial injury and increasing expression of occludin. 16S rRNA sequencing results showed that LGS remarkably modulated gut microbiota structure in ALD mice via recovering alcohol-induced microbial changes and specifically mediating enrichment of several bacterial genera (Alloprevotella, Monoglobus, Erysipelatoclostridium Parasutterella, Harryflintia and unclassified_c_Clostridia). Further study revealed that LGS increased production of SCFAs of hexanoic acid in cecum, promoted alcohol-mediated reduction of GRP43 expression in ileum, and increased serum GLP-1 level.

Discussion: Overall, LGS exerts a remarkable protective effect on ALD mice through the gut microbiota mediated specific hexanoic acid production and GPR43/GLP-1 pathway.

Keywords: GLP-1; GPR43; Liuweizhiji Gegen-Sangshen beverage; SCFAs; alcoholic liver disease; gut microbiota.

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. The present study was financially supported by the Sichuan Science and Technology Program, China (Grant Nos. 2022YFS0624 and 2024MS219), the Luzhou Science and Technology Program, China (Grant Nos. 2022YFS0624-B3, 2022YFS0 624-B1 and 2024SYF161), the grant from Sichuan Province Administration of Traditional Chinese Medicine (Grant No. 2023zd008).