Gut Microbiota-Derived Metabolites in Skeletal Muscle Insulin Resistance: A Gut-Muscle Axis Perspective

Insulin resistance (IR) is a core pathological basis of metabolic diseases such as type 2 diabetes mellitus (T2DM), and skeletal muscle is the primary target organ for insulin-mediated glucose uptake and utilization. Gut microbiota can directly regulate skeletal muscle insulin resistance through molecular mechanisms such as epigenetic regulation, incretin signaling, and signal transduction. They can also indirectly exert effects by influencing mitochondrial function and microcirculatory perfusion. Notably, the interaction between intestinal barrier dysfunction and microcirculatory perfusion impairment can further amplify insulin resistance. Furthermore, alterations in skeletal muscle biomechanical properties represent an emerging direction in gut-muscle axis research. This review provides a comprehensive perspective on the gut-muscle axis, offering a theoretical basis for the development of novel therapeutic targets based on gut microbiota.