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World J Gastroenterol. Dec 28, 2020; 26(48): 7603-7618
Published online Dec 28, 2020. doi: 10.3748/wjg.v26.i48.7603
Gut microbiota mediated molecular events and therapy in liver diseases
Xiaoqiang Qi, Ming Yang, Joseph Stenberg, Rahul Dey, Leslie Fogwe, Muhammad Shawkat Alam, Eric T Kimchi, Kevin F Staveley-O'Carroll, Guangfu Li
Xiaoqiang Qi, Ming Yang, Joseph Stenberg, Rahul Dey, Leslie Fogwe, Muhammad Shawkat Alam, Eric T Kimchi, Kevin F Staveley-O'Carroll, Guangfu Li, Department of Surgery, University of Missouri, Columbia, MO 65212, United States
Xiaoqiang Qi, Ming Yang, Eric T Kimchi, Kevin F Staveley-O'Carroll, Guangfu Li, Ellis Fischel Cancer Center, University of Missouri, Columbia, MO 65212, United States
Xiaoqiang Qi, Ming Yang, Eric T Kimchi, Kevin F Staveley-O'Carroll, Guangfu Li, VA Hospital, Harry S Truman Memorial VA Hospital, Columbia, MO 65201, United States
Guangfu Li, Department of Molecular Microbiology and Immunology, University of Missouri, Columbia, MO 65212, United States
Author contributions: Qi X, Yang M, and Stenberg J collected data, wrote the paper, and contributed equally; Dey R, Fogwe L, and Alam MS collected data and partly drafted the paper's first version; Kimchi ET, Staveley-O’Carroll KF, and Li G designed, revised, and finalized the manuscript, co-corresponding authors.
Supported by NIH Grant, No. R01CA208396; and VA Merit Award, No. I01 BX004065-1.
Conflict-of-interest statement: The authors declare no conflict of interest.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Guangfu Li, DVM, PhD, Assistant Professor, Department of Surgery, University of Missouri, 230 Jesse Hall, Columbia, MO 65212, United States. liguan@health.missouri.edu
Received: October 20, 2020
Peer-review started: October 20, 2020
First decision: November 13, 2020
Revised: November 24, 2020
Accepted: December 6, 2020
Article in press: December 6, 2020
Published online: December 28, 2020
Processing time: 65 Days and 18.9 Hours
Abstract

Gut microbiota is a community of microorganisms that reside in the gastrointestinal tract. An increasing number of studies has demonstrated that the gut-liver axis plays a critical role in liver homeostasis. Dysbiosis of gut microbiota can cause liver diseases, including nonalcoholic fatty liver disease and alcoholic liver disease. Preclinical and clinical investigations have substantiated that the metabolites and other molecules derived from gut microbiota and diet interaction function as mediators to cause liver fibrosis, cirrhosis, and final cancer. This effect has been demonstrated to be associated with dysregulation of intrahepatic immunity and liver metabolism. Targeting these findings have led to the development of novel preventive and therapeutic strategies. Here, we review the cellular and molecular mechanisms underlying gut microbiota-mediated impact on liver disease. We also summarize the advancement of gut microbiota-based therapeutic strategies in the control of liver diseases.

Keywords: Gut microbiota; Intrahepatic immunity; Metabolite; Fecal microbial transplantation; Probiotic; Antibiotic

Core Tip: Accumulating evidence shows that gut microbiota plays a critical role in liver pathophysiology and targeting gut microbiota is a potential treatment option for chronic liver disease. Herein, this review explores the cellular and molecular mechanisms of how gut microbiota contributes to liver diseases, including alcohol-induced and nonalcohol-induced liver fatty liver diseases, liver fibrosis, cirrhosis, and cancer. This review also summarizes the current gut microbiota-based therapeutic strategies and discusses future directions in promoting gut microbiota-based therapy for liver diseases.