Abstract

Background and aims: The gut microbiota is a complex ecosystem containing bacteria, viruses, fungi, yeasts and other single-celled organisms. It is involved in the development and maintenance of both innate and systemic immunity of the body. Emerging evidence has shown its role in liver diseases through the immune system cross-talk. We review herein literature data regarding the triangular interaction between gut microbiota, immune system and liver in health and disease. Methods: We conducted a search on the main medical databases for original articles, reviews, meta-analyses, randomized clinical trials and case series using the following keywords and acronyms and their associations: gut microbiota, microbiome, gut virome, immunity, gastrointestinal-associated lymphoid tissue (GALT), non-alcoholic fatty liver disease (NAFLD), non-alcoholic steato-hepatitis (NASH), alcoholic liver disease, liver cirrhosis, hepatocellular carcinoma. Results: The gut microbiota consists of microorganisms that educate our systemic immunity through GALT and non-GALT interactions. The latter maintain health but are also involved in the pathophysiology and in the outcome of several liver diseases, particularly those with metabolic, toxic or immune-mediated etiology. In this context, gut virome has an emerging role in liver diseases and needs to be further investigated, especially due to the link reported between severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection and hepatic dysfunctions. Conclusions: Changes in gut microbiota composition and alterations in the immune system response are involved in the pathogenesis of metabolic and immune-mediated liver diseases.

Highlights

  • The human microbiota, considered as a functional organ in se, consists of a complex community of microorganisms, living on our skin and mucosal tissues, forming an efficient ecosystem with the body [1,2].Despite the apparent alliance between gut microbiota and its host, this intimate relationship poses a permanent threat to the host’s health, requiring constant control

  • Since the epidemiology of chronic liver diseases is changing, due to the decreasing rate of viral hepatitis and the increasing new epidemic of a wide spectrum of alcoholic and non-alcoholic fatty liver disease (NAFLD) [6,7], we focus our attention on non-viral hepatitis

  • Due to the link reported between severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection and hepatic dysfunctions, we outline the emerging role of the gut virome in liver diseases

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Summary

Introduction

The human microbiota, considered as a functional organ in se, consists of a complex community of microorganisms (bacteria, yeasts, fungi, archea, protozoa and virus), living on our skin and mucosal tissues, forming an efficient ecosystem with the body [1,2]. The role of the human immune system in fine-tuning and shaping the microbiota is of paramount importance [3]. The liver produces bile that flows to the gut directly and influences the resident microbial environment [4]. This circulatory loop between liver and gut is an explicative tale of how changes in the gut flora can have both beneficial and/or harmful consequences for the host [5]. This review summarizes the evidences on the triangular interaction between gut microbiota, immune system and liver, in health and disease. Due to the link reported between severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection and hepatic dysfunctions, we outline the emerging role of the gut virome in liver diseases

Methods
Gut Microbiota Composition and Main Functions
GALT and Non-GALT Systems and Their Interactions with Gut Microbiota
Adaptive Immunity
Alcoholic Liver Disease
Non-Alcoholic Fatty Liver Disease
Autoimmune Diseases
Liver Cirrhosis
Gut Virome and Liver Diseases at the Time of SARS-COV-2 Pandemic
Findings
Conclusions
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