Bridging the gap between microbiome function and clinical benefit in sarcopenia

We read the recent systematic review and meta-analysis on nutrition-based, gut microbiota-targeted interventions for sarcopenia in older adults with great interest. While the evidence suggests that probiotics and fiber-enriched diets may improve surrogate outcomes such as muscle strength and gait speed, we highlight two priorities to strengthen future mechanistic and clinical translation. First, microbiome measurements in existing trials are often limited to genus-level taxonomic shifts, which can be biologically misleading because a single genus may include members with divergent immunomodulatory properties. Even species-level profiling may be insufficient, as strains within the same species can differ markedly in genetic content and metabolic capacity. Moreover, taxonomic composition does not necessarily reflect functional output due to functional redundancy across microbial communities. We therefore recommend transitioning to whole-genome shotgun metagenomics to enable strain-level resolution and functional profiling, allowing investigators to quantify pathways and metabolites relevant to muscle preservation, including short-chain fatty acids and vitamin biosynthesis. Second, we argue that improvements in sarcopenia-defining parameters should be linked to patient-centered clinical benefit. Future randomized controlled trials should be adequately powered to assess hard endpoints, including falls, fractures, hospitalization rates, and functional independence, alongside muscle mass and performance measures, to establish whether microbiota modulation delivers meaningful reductions in healthcare burden.