Gut Microbiome-Mediated Alteration of Immunity, Inflammation, and Metabolism Involved in the Regulation of Non-alcoholic Fatty Liver Disease

Abstract

Non-alcoholic fatty liver disease (NAFLD) is one of the leading causes of end-stage liver disease, leading to a rapidly growing global public health burden. The term “gut microbiome (GM)” refers to the approximately 100 trillion microbial cells that inhabit the host’s gastrointestinal tract. There is increasing evidence that GM is involved in the pathogenesis of NAFLD and may be a potential target for intervention. To explore GM-based strategies for precise diagnosis and treatment of NAFLD, great efforts have been made to develop a comprehensive and in-depth understanding of the host–microbe interaction. This review evaluates this interaction critically, mainly considering the intricate regulation of the metabolism, immunity, and inflammatory status during the evolution of the disease pathogenesis, revealing roles for the GM in NAFLD by examining advances in potential mechanisms, diagnostics, and modulation strategies.Synopsis: Considering the intricate metabolic and immune/inflammatory homeostasis regulation, we evaluate the latest understanding of the host–microbe interaction and reveal roles for the gastrointestinal microbiome in NAFLD. Strategies targeting the gastrointestinal microbiome for the diagnosis and treatment of NAFLD are proposed.

Polydextrose Alleviates Adipose Tissue Inflammation and Modulates the Gut Microbiota in High-Fat Diet-Fed Mice

“…Moreover, we found that PDX treatment significantly modulated the gut microbiota structure in obese mice. Previous studies have indicated that gut microbiota dysbiosis is one of the reasons for obesity and related disorders, and fecal microbial transplantation (FMT) is considered a potential source of novel therapeutics (Napolitano and Covasa, 2020;He et al, 2021;Voland et al, 2021). FMT from the obesity-associated human gut microbiota to mice can induce vascular dysfunction and glucose intolerance, and FMT from lean donors to patients with obesity can promote metabolic benefits (Mocanu et al, 2021;Russo et al, 2021).…”

Combined Use of Bicyclol and Berberine Alleviates Mouse Nonalcoholic Fatty Liver Disease

“…Consequently, the abnormal hepatic lipid metabolism is involved in sustained inflammation response and liver injury, further leading to the progression of NAFLD (Dong et al, 2021;Orabi et al, 2021). Apart from the aberrant hepatic lipid metabolism, gut microbiome-mediated alteration of immunity, inflammation, and metabolism are also involved in the regulation of NAFLD (He et al, 2021). Currently, no specific drug has been approved to treat NAFLD, though several candidate drugs with different mechanisms of action have been tested in clinical trials (Brown et al, 2021), which target different pathophysiological pathways towards NAFLD, such as metabolic targets, inflammatory pathways, liver-gut axis, and antifibrotic targets.…”

“…Consequently, the abnormal hepatic lipid metabolism is involved in sustained inflammation response and liver injury, further leading to the progression of NAFLD ( Dong et al, 2021 ; Orabi et al, 2021 ). Apart from the aberrant hepatic lipid metabolism, gut microbiome-mediated alteration of immunity, inflammation, and metabolism are also involved in the regulation of NAFLD ( He et al, 2021 ).…”

Microbiota in Pancreatic Diseases: A Review of the Literature

“…NAFPD and nonalcoholic fatty liver disease (NAFLD) have been linked to metabolic syndrome, and they likely share a similar pathogenesis [94,95]. The gut microbiota may trigger NAFLD through several mechanisms: Increase in intestinal permeability, modulation of the innate immune system, alteration of bile acid turnover, increase in endogenous ethanol production, and triggering of direct and indirect inflammatory stimuli [96]. Similar mechanisms could be claimed for the pathogenesis of NAFPD.…”