Gut microbiota and metabolite interface-mediated hepatic inflammation

Abstract

Immunologic and metabolic signals regulated by gut microbiota and relevant metabolites mediate bidirectional interaction between the gut and liver. Gut microbiota dysbiosis, due to diet, lifestyle, bile acids, and genetic and environmental factors, can advance the progression of chronic liver disease. Commensal gut bacteria have both pro- and anti-inflammatory effects depending on their species and relative abundance in the intestine. Components and metabolites derived from gut microbiota-diet interaction can regulate hepatic innate and adaptive immune cells, as well as liver parenchymal cells, significantly impacting liver inflammation. In this mini review, recent findings of specific bacterial species and metabolites with functions in regulating liver inflammation are first reviewed. In addition, socioeconomic and environmental factors, hormones, and genetics that shape the profile of gut microbiota and microbial metabolites and components with the function of priming or dampening liver inflammation are discussed. Finally, current clinical trials evaluating the factors that manipulate gut microbiota to treat liver inflammation and chronic liver disease are reviewed. Overall, the discussion of microbial and metabolic mediators contributing to liver inflammation will help direct our future studies on liver disease.

Keywords: chronic liver disease; clinical trials; gut microbiota; liver inflammation; metabolic regulation; metabolite.

Figure 1.

The roles of gut microbiota and metabolites in liver inflammation and potential regulatory factor. Gut microbiota dysbiosis impacts liver inflammation, accompanying the infiltration of pro-inflammatory cells (eg, macrophages and neutrophils), secretion of inflammatory cytokines (eg, TNF-α, IL-1β, and IFN-γ), hepatic cell apoptosis, lipid accumulation, and oxidative stress. Alteration of gut microbiota including the increase of pathogenic bacteria and decrease of beneficial bacteria can change the products of secondary bile acids and metabolites such as alcohol and indole metabolism to promote liver inflammation. Factors including diet, drink, exercise, stress, genetic factors, drugs, and hormones can regulate the change of gut microbiota to treat liver inflammation. IFN-γ, interferon-γ; IL-1β, interleukin-1β; TNF-α, tumor necrosis factor-α. The figure was prepared using Biorender (https://biorender.com).