Gut–Liver Axis and Non-Alcoholic Fatty Liver Disease: A Vicious Circle of Dysfunctions Orchestrated by the Gut Microbiome

Abstract

Non-alcoholic fatty liver disease (NAFLD) is a prevalent, multifactorial, and poorly understood liver disease with an increasing incidence worldwide. NAFLD is typically asymptomatic and coupled with other symptoms of metabolic syndrome. The prevalence of NAFLD is rising in tandem with the prevalence of obesity. In the Western hemisphere, NAFLD is one of the most prevalent causes of liver disease and liver transplantation. Recent research suggests that gut microbiome dysbiosis may play a significant role in the pathogenesis of NAFLD by dysregulating the gut–liver axis. The so-called “gut–liver axis” refers to the communication and feedback loop between the digestive system and the liver. Several pathological mechanisms characterized the alteration of the gut–liver axis, such as the impairment of the gut barrier and the increase of the intestinal permeability which result in endotoxemia and inflammation, and changes in bile acid profiles and metabolite levels produced by the gut microbiome. This review will explore the role of gut–liver axis disruption, mediated by gut microbiome dysbiosis, on NAFLD development.

Glucagon-like Peptide-1 Receptor Agonists in Patients with Type 2 Diabetes Mellitus and Nonalcoholic Fatty Liver Disease—Current Background, Hopes, and Perspectives

“…The gut microbiome plays an important role in the occurrence and development of NAFLD and T2DM, and can therefore emerge as a forthcoming target in the therapy of these metabolic diseases [ 96 , 97 ]. Animal studies provide some evidence that liraglutide has a beneficial impact on components of the intestinal flora that are related to inflammation and glucolipid metabolism, thus improving the fatty liver disease [ 98 ].…”

Association between gut microbiota and hepatocellular carcinoma from 2011 to 2022: Bibliometric analysis and global trends

“…It can also influence the production of other hormones and signaling molecules that affect the growth and activity of other bacterial species ( 43 ). When the intestinal flora is damaged, the intestinal mucosal barrier and immune functions is destroyed, leading to intestinal endotoxemia (IETM), bacterial translocation, and excessive absorption of bacterial metabolites ( 44 , 45 ). These factors contribute to the process of liver cell inflammation, damage, and repair, especially on the basis of the original liver disease, HCC can develop due to hepatocyte damage and repair during inflammation.…”

Microbiome Dysbiosis: A Pathological Mechanism at the Intersection of Obesity and Glaucoma

“…These microorganisms play an essential role in nutrient absorption, energy regulation, and the health of the mucosal barrier [ 74 , 75 , 76 ]. Dysbiosis in the gut microbiome has been linked to metabolic diseases such as obesity [ 14 , 15 ] and chronic liver diseases [ 15 , 16 , 17 ]. Changes in the microbiome may influence energy balance and dysregulate immunological responses in obese individuals by inducing intestinal barrier dysfunction, leading to the translocation of bacteria across the epithelial barrier and triggering systemic inflammation [ 14 , 15 ].…”

“…There is growing interest in microbiome dysbiosis, particularly in the gut, which has been widely acknowledged to play a role in the etiology of metabolic illnesses such as obesity [ 14 , 15 ] and chronic liver diseases [ 15 , 16 , 17 ]. On the other hand, there is increasing evidence that microbiome dysbiosis plays a critical role in the onset and progression of several degenerative diseases of the central nervous system [ 18 ] and the retina [ 19 , 20 , 21 ], as well as in the development and progression of several ocular diseases [ 22 , 23 , 24 ].…”