The roles of the gut microbiota, metabolites, and epigenetics in the effects of maternal exercise on offspring metabolism.

Metabolic diseases, including obesity, dyslipidemia, and type 2 diabetes, have become severe challenges worldwide. The Developmental Origins of Health and Disease (DOHaD) hypothesis suggests that an adverse intrauterine environment can increase the risk of metabolic disorders in offspring. Studies have demonstrated that maternal exercise is an effective intervention for improving the offspring metabolic health. However, the pathways through which exercise works are unclear. It has been reported that the gut microbiota mediates the effect of maternal exercise on offspring metabolism, and epigenetic modifications have also been proposed to be important molecular mechanisms. Microbial metabolites can influence epigenetics by providing substrates for DNA or histone modifications, binding to G-protein-coupled receptors to affect downstream pathways, or regulating the activity of epigenetic modifying enzymes. This review aims to summarize the intergenerational effect of maternal exercise and proposes that gut microbiota-metabolites-epigenetic regulation is an important mechanism by which maternal exercise improves offspring metabolism, which may yield novel targets for the early prevention and intervention of metabolic diseases.