The role of the gut microbiome and exercise in non-alcoholic fatty liver disease

Abstract

In recent years, the human gut microbiome has been found to influence a multitude of non-communicable diseases such as cardiovascular disease and metabolic syndrome, with its components type 2 diabetes mellitus and obesity. It is recognized to be mainly influenced by environmental factors, such as lifestyle, but also genetics may play a role. The interaction of gut microbiota and obesity has been widely studied, but in regard to non-alcoholic fatty liver disease (NAFLD) as a manifestation of obesity and insulin resistance, the causal role of the gut microbiome has not been fully established. The mechanisms by which the gut microbiome influences lipid accumulation, inflammatory responses, and occurrence of fibrosis in the liver are a topic of active research. In addition, the influence of exercise on gut microbiome composition is also being investigated. In clinical trials, exercise reduced hepatic steatosis independently of weight reduction. Other studies indicate that exercise may modulate the gut microbiome. This puts forward the question whether exercise could mediate its beneficial effects on NAFLD via changes in gut microbiome. Yet, the specific mechanisms underlying this potential connection are largely unknown. Thus, associative evidence from clinical trials, as well as mechanistic studies in vivo are called for to elucidate the relationship between exercise and the gut microbiome in NAFLD. Here, we review the current literature on exercise and the gut microbiome in NAFLD.

Keywords: exercise; gut microbiome; insulin resistance; non-alcoholic fatty liver disease; obesity; type 2 diabetes mellitus.

Figure 1.

Mechanisms by which exercise and gut microbiome may affect NAFLD. (A) Sedentary situation. Overview of the pathogenesis of NAFLD and the relationship of the gut microbiome in the pathogenesis. A sedentary lifestyle has led to the accumulation of TGs in the liver, due to IR in the peripheral organs and the liver itself, resulting in the production of ROS, and therefore, inflammation and further fibrosis. Dysbiosis and increased gut permeability allow LPS derived from gram-negative bacteria and ethanol synthesized from EtOH-producing bacteria to reach the liver through the portal vein and drive lipid accumulation and inflammation in the liver. (B) Physically active situation. Simplified overview of the beneficial effects of exercise and the gut microbiome on NAFLD. IR is ameliorated by exercise increasing insulin sensitivity, and normalizing lipid metabolism in peripheral tissues and in the liver. Exercise affects the gut microbiota composition, and this increases the abundance of SCFA-producing bacteria and thereby increases the production of SCFAs that can reach the liver. EtOH, ethanol; FFA, free fatty acids; IR, insulin resistance; LPS, lipopolysaccharide; NAFLD, non-alcoholic fatty liver disease; NASH, non-alcoholic steatohepatitis; ROS, reactive oxygen species; SCFA, short-chain fatty acid; TGs, triglycerides.