Nonalcoholic Fatty Liver Disease and Gut-liver Axis: Role of Intestinal Microbiota and Therapeutic Mechanisms

Abstract

The correlation between gut, secreted metabolites, and hepatic diseases has strengthened over the last decade. Interactions of intestinal permeability, gut microbes, and derived metabolites influence the development and progression of nonalcoholic fatty liver disease (NAFLD), a prevalent disease that affects more than 30% of the global population. NAFLD is now called metabolic dysfunction-associated steatotic liver disease (MASLD) to better reflect the disease process. Here, we describe mechanisms of NAFLD development, the role of gut bacteria, gut metabolites, interventions for diagnosis, and the prognosis of NAFLD. We discuss new paradigms that challenge the conventional, addressing disease etiology and translational approaches in a new dimension. Previous studies shed light on intricate relationships of the gut microbiome with the liver, or the gut-liver axis. Bidirectional communication between the gut and the liver involves exchange of metabolites, immune signaling, and inflammatory responses that has potential for novel NAFLD/nonalcoholic steatohepatitis (NASH) treatments. In this review, we propose exploring functional metagenomics to develop NAFLD diagnostic methods and risk assessment. The prospects of genetic engineering, fecal transplants, and specialized diet as targets of novel therapeutic regimes to combat NAFLD/NASH are discussed. Changes in lifestyle and diet in the population, combined with genetic predisposition, have led to an increasing number of cases of NAFLD. The microbiome responds to diet, exercise, and the environment, and can modulate NAFLD in cases with surgical impediments. It is thus vital to explore its emerging roles in human healthcare and not only liver disease.