Probiotics, prebiotics, and synbiotics to counteract sarcopenia: where are we now and what challenges need to be faced?

Sarcopenia, the age-related decline in muscle mass and strength, is a contributor to frailty and reduced quality of life. Emerging evidence suggests an emerging role of the gut microbiome in modulating skeletal muscle through microbial species and metabolites, such as short-chain fatty acids (SCFAs), potentially influencing inflammation, nutrient absorption, and glucose and protein metabolism. This review considers the potential of probiotics, prebiotics, and synbiotics as interventions to mitigate sarcopenia based on animal and human studies, while providing a critique of present barriers that need to be addressed. Preclinical models, including germ-free mice and faecal microbiota transplantation, demonstrate that gut microbiota from healthy or young donors may enhance overall muscle health via reductions in inflammatory and muscle atrophy markers. Limited human studies show that probiotics such as <i>Lactobacillus</i> and <i>Bifidobacterium</i> could improve branched-chain amino acid (BCAA) bioavailability and potentially sarcopenia indices, although findings have been inconsistent. Particularly, challenges including inconsistent microbial assessments, lack of dietary control and interindividual variability due to diet, age, genetics, comorbidities and medications may hinder progress in this field. Delivery methods (e.g. capsules, fermented foods or fortified products) could further complicate efficacy through probiotic stability and dietary restrictions in older adults. Standardised protocols [e.g. Strengthening The Organisation and Reporting of Microbiome Studies (STORMS) checklist] and multi-omics approaches may be critical to address these limitations and identify microbial signatures linked to sarcopenia outcomes. While preclinical evidence highlights mechanistic pathways pertinent to amino acid metabolism, translating findings to humans requires rigorous experimental trials.