Abstract

Alcoholic hepatitis (AH) has a high short-term mortality rate. Schisandra chinensis has the potential to ameliorate liver damage and be a source of prebiotics. We aimed to investigate whether Schisandra chinensis extract (SCE) can improve AH and the role of the small intestinal and cecal microbiota and their metabolites. UHPLC-QE-MS was used to analyze the chemical components of SCE. The chronic-plus-binge ethanol feeding model was used to induce AH in mice. 1H NMR was used to analyze intestinal metabolites. 16S rRNA-based high throughput sequencing was used to evaluate the effects of SCE on intestinal microbiota (IM). Intestinal microbiota transplantation was used to explore the role of IM in SCE treatment of AH. SCE ameliorated AH non-dose-dependently. SCE effectively improved liver inflammation and oxidative/nitrosative stress, strengthened intestinal barrier function, and regulated the composition of IM and the content of short-chain fatty acids (SCFAs) in AH mice. Samples from in vivo and in vitro SCE-altered IM improved liver status and regulated the IM. The administration of Lactobacillus plantarum and Bifidobacterium breve ameliorated AH to some extent. The administration of Enterococcus faecalis and Klebsiella oxytoca had partial beneficial effects on AH. Collectively, IM and metabolites were closely associated with the improvement of SCE on AH. The possible microbe targets were the growth inhibition of Escherichia-Shigella and the expansion of SCFA producers, such as Lactobacillus and Bifidobacterium. Schisandra chinensis can be considered as a safe and effective dietary supplement for the prevention and improvement of AH.

Highlights

  • Alcoholic hepatitis (AH) is the most common form of alcoholic liver disease (ALD), with a short-term mortality rate of up to 50% [1]

  • Schisandra chinensis extract (SCE) had a limited effect on alcohol metabolism, the results demonstrated that SCE administration inhibited oxidative stress

  • Substantial reports suggested that changes in gut microbiota are an important part of the pathogenesis of AH

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Summary

Introduction

Alcoholic hepatitis (AH) is the most common form of alcoholic liver disease (ALD), with a short-term mortality rate of up to 50% [1]. Intestinal Microbiota and Alcoholic Hepatitis (SCFAs), intestinal microbial metabolites that influence intestinal motility and enhance intestinal barrier functions by regulating the function of intestinal epithelial cells, were reduced [4]. These changes lead to increased intestinal permeability and the delivery of bacterial lipopolysaccharide (LPS) into the liver via the portal vein, which activates Kupffer cells to produce inflammatory mediators, such as tumor necrosis factor alpha (TNF-α) and interleukin-1 (IL-1), leading to liver injury [3, 5]. Little is known regarding the relationship between Schisandra chinensis extract (SCE)-regulated intestinal microbiota (IM) and AH

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