Gut Microbiota and Chemical-Induced Acute Liver Injury.

Tao Chen,Peng Chen,Rui Li

doi:10.3389/fphys.2021.688780

Tao Chen, Peng Chen + Show 1 more

Open Access

https://doi.org/10.3389/fphys.2021.688780

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Abstract

Background: Drug overdose or chemical exposures are the main causes of acute liver injury (ALI). Severe liver injury can develop into liver failure that is an important cause of liver-related mortality in intensive care units in most countries. Pharmacological studies have utilized a variety of comprehensive chemical induction models that recapitulate the natural pathogenesis of acute liver injury. Their mechanism is always based on redox imbalance-induced direct hepatotoxicity and massive hepatocyte cell death, which can trigger immune cell activation and recruitment to the liver. However, the pathogenesis of these models has not been fully stated. Many studies showed that gut microbiota plays a crucial role in chemical-induced liver injury. Hepatotoxicity is likely induced by imbalanced microbiota homeostasis, gut mucosal barrier damage, systemic immune activation, microbial-associated molecular patterns, and bacterial metabolites. Meanwhile, many preclinical studies have shown that supplementation with probiotics can improve chemical-induced liver injury. In this review, we highlight the pathogenesis of gut microorganisms in chemical-induced acute liver injury animal models and explore the protective mechanism of exogenous microbial supplements on acute liver injury.

Highlights

Acute liver injury (ALI) is a common disease that seriously threatens the life and health of the patients
In the chemical-induced acute liver injury (ALI) models, the main mechanisms of gut microbiota in regulating ALI can be summarized by three points (Figure 2)
The intestinal microbes directly affect the detoxification ability of hepatocyte through the changes of bacterial metabolites and the transformation of chemical toxins; secondly, microbes and microbial-associated molecular patterns (MAMPs) are exposed to the systemic immune cells through the damaged intestinal mucosal barrier

Summary

Background

Drug overdose or chemical exposures are the main causes of acute liver injury (ALI). Pharmacological studies have utilized a variety of comprehensive chemical induction models that recapitulate the natural pathogenesis of acute liver injury. Their mechanism is always based on redox imbalance-induced direct hepatotoxicity and massive hepatocyte cell death, which can trigger immune cell activation and recruitment to the liver. Many studies showed that gut microbiota plays a crucial role in chemical-induced liver injury. Many preclinical studies have shown that supplementation with probiotics can improve chemical-induced liver injury. We highlight the pathogenesis of gut microorganisms in chemical-induced acute liver injury animal models and explore the protective mechanism of exogenous microbial supplements on acute liver injury

INTRODUCTION

Findings

CONCLUSION