Exercise-Induced Short-Chain Fatty Acids: A Novel Therapeutic Target in Type 2 Diabetes Mellitus with Sarcopenia.

Abstract

Type 2 diabetes mellitus accompanied by sarcopenia is an emerging clinical challenge in aging populations, characterized by coexisting metabolic dysfunction and the progressive loss of skeletal muscle mass and function. This comorbidity substantially elevates the risk of frailty, functional impairment, and poor clinical outcomes, highlighting the urgent need for targeted therapeutic interventions. Growing evidence suggests that gut microbiota dysbiosis contributes to the pathogenesis of both Type 2 diabetes mellitus and sarcopenia through mechanisms such as chronic inflammation, insulin resistance, and mitochondrial and autophagic dysfunction. Among gut-derived metabolites, short-chain fatty acids exert anti-inflammatory and insulin-sensitizing effects and also promote muscle metabolism and mitochondrial function. Notably, exercise increases the abundance of short-chain fatty acid-producing bacteria, thereby elevating circulating short-chain fatty acid levels and contributing to improved glucose homeostasis and skeletal muscle function. This review summarizes the effects of various exercise modalities on short-chain fatty acid production and explores the mechanisms by which short-chain fatty acids mediate the benefits of exercise in Type 2 diabetes mellitus complicated by sarcopenia, emphasizing their potential as novel therapeutic targets for integrated disease management.