The Gut-Muscle Axis in Sarcopenia: Mechanisms, Evidence Gaps and Translational Challenges

Sarcopenia is an age-related skeletal muscle disorder characterized by reduced muscle mass, strength, and physical performance, as well as increased risk of disability, hospitalization, and mortality. Emerging evidence suggests that gut microbiota alterations may contribute to muscle decline via a microbiota-gut-muscle axis, acting as a context-dependent modulator rather than a primary causal driver. This narrative review synthesizes mechanistic, clinical, and translational evidence linking gut dysbiosis to sarcopenia. Preclinical studies show that microbiota modulation (e.g., antibiotics, probiotics, prebiotics, postbiotics, fecal microbiota transplantation) affects muscle mass, strength, and metabolism through pathways including inflammation, mitochondrial dysfunction, altered short-chain fatty acid production, and impaired anabolic signaling. In humans, observational studies associate lower microbial diversity and reduced short-chain fatty acid-producing taxa with poorer muscle outcomes, but findings are heterogeneous and non-causal. Interventional trials remain limited and characterized by small sample sizes, with effects more consistent for functional outcomes than muscle mass. Overall, the gut microbiota represents a modifiable contributor within the complex biology of sarcopenia. Future studies should integrate microbiome profiling and multi-omics approaches within well-designed clinical trials to identify responder phenotypes and define the role of microbiota-targeted strategies within multimodal interventions.