Gut microbiota, sarcopenia, and type 2 diabetes: a triangular pathophysiological network.

Purpose: Type 2 diabetes mellitus (T2DM), sarcopenia, and gut microbiota dysbiosis are increasingly recognized as interrelated conditions. T2DM accelerates muscle wasting through insulin resistance, inflammation, and oxidative stress, while sarcopenia worsens metabolic dysfunction. This review explores the interconnected conditions of Type 2 Diabetes, sarcopenia, and gut microbiota dysbiosis, highlighting their therapeutic potential and the need for interventions targeting these conditions for metabolic and musculoskeletal health. Methods: An extensive literature search was performed in PubMed, EMBASE, Scopus, and Web of Science up to July 2025 using terms related to gut microbiota, sarcopenia, and T2DM. Both preclinical and human studies were included if they addressed microbial composition, metabolites, inflammation, insulin resistance, or muscle protein turnover. Results: Evidence indicates bidirectional relationships: T2DM patients show higher prevalence of sarcopenia, while reduced muscle mass increases T2DM risk. Gut dysbiosis in T2DM is characterized by depletion of SCFA-producing taxa (e.g., Faecalibacterium prausnitzii) and enrichment of endotoxin-producing bacteria, leading to systemic inflammation and impaired insulin signaling. Germ-free and antibiotic-treated rodent models demonstrate muscle atrophy, whereas probiotic or prebiotic supplementation restores muscle mass and improves glucose metabolism. Limited clinical trials suggest dietary fibre, probiotics, and fecal microbiota transplantation improve glycemic control and inflammatory markers, with potential secondary benefits on muscle function. Conclusion: T2DM, sarcopenia, and gut microbiota are linked through insulin resistance, inflammation, and altered signaling. Targeting gut-muscle-metabolism axis through diet, microbiota modulation, and exercise is promising. Future longitudinal and interventional studies are needed to establish causality and develop precision microbiome-based therapies. Summary: Type 2 diabetes mellitus (T2DM), sarcopenia, and gut microbiota dysbiosis are interconnected in a triangular pathophysiological network. T2DM accelerates muscle loss through insulin resistance, inflammation, and oxidative stress, while sarcopenia worsens glycaemic control. Gut dysbiosis reduces beneficial short-chain fatty acid (SCFA) production and increases pro-inflammatory metabolites such as lipopolysaccharides, further impairing muscle metabolism and glucose regulation. Preclinical and emerging clinical evidence shows that dietary fibre, probiotics, and fecal microbiota transplantation can modulate this axis. Targeting the gut-muscle-metabolism triad offers promising integrative strategies for preventing and managing diabetic sarcopenia.