The role of exercise intensity in the regulation of the gut microbiota and liver function in metabolic dysfunction–associated steatotic liver disease

Metabolic dysfunction–associated steatotic liver disease is currently regarded as one of the most prevalent metabolic disorders, closely linked to obesity, insulin resistance, and disturbances of the gut microbiome. Physical exercise is a key nonpharmacological strategy capable of modulating energy and metabolic homeostasis through its effects on interorgan communication along the gut–liver axis. This review summarizes experimental and clinical evidence regarding the effects of different types of physical activity, such as moderate-intensity continuous training and high-intensity interval training, on intestinal barrier integrity, hepatic lipid metabolism, mitochondrial and endoplasmic reticulum homeostasis, and systemic inflammation. Preclinical studies demonstrate that both training modalities increase the expression of tight junction proteins (ZO-1, occludin, JAM-A), enhance gut microbiota diversity, reduce endotoxemia, and attenuate the severity of steatosis. High-intensity interval training was superior in stimulating mitochondrial biogenesis, β-oxidation, and irisin secretion, as well as in reducing endoplasmic reticulum stress and macrophage-mediated inflammation. Clinical data confirm that regular physical activity, regardless of intensity, decreases hepatic fat accumulation and improves insulin sensitivity and cardiovascular function. However, clinical evidence remains limited, underscoring the need for further investigation of the molecular regulation mechanisms of the gut–liver axis. Overall, physical activity, particularly high-intensity interval training, is an effective, safe, and affordable approach for the prevention and treatment of metabolic dysfunction–associated steatotic liver disease, contributing to the restoration of metabolic balance and hepatic homeostasis.