Probiotic supplementation as a nutritional strategy for the prevention and management of sarcopenia in older adults

Abstract

Introduction Sarcopenia, defined as the loss of skeletal muscle mass, strength, and functional capacity over time, poses a significant health burden among older adults. A growing body of evidence indicates that the gut microbiota contributes to inflammation and metabolic regulation, mitochondrial function, and anabolic signaling, thereby shaping the gut–muscle axis. Probiotic supplementation has gained traction as a nutritional approach for the regulation of microbiome-derived metabolites. The present study aims to assess the rationale for probiotic supplementation to prevent and manage sarcopenia in older individuals. Methods Using data from NHANES (2011–2018; n = 3,500), UK Biobank (n = 5,000), and GMrepo (n = 800), we examined associations between probiotic exposure and muscle outcomes, inflammation, and microbiome diversity. C2C12 myotubes were used in vitro under probiotic-conditioned media (PCM). The interactions of short-chain fatty acids (SCFAs) with the regulatory proteins (mTOR, AMPK, NF-κB) were evaluated using molecular docking simulations. Random Forest and XGBoost models were used to predict sarcopenia risk using integrated multimodal features, with a 70% training and 30% validation split. Results Probiotic users exhibited greater handgrip strength (UK Biobank: 27.2 ± 4.8 kg vs. 25.1 ± 5.2 kg), higher fat-free mass (57.4 ± 10.6 kg vs. 56.2 ± 11.0 kg), and lower inflammatory burden compared to non-users. PCM increased fusion index (85.6 ± 2.3% vs. 78.9 ± 3.2%, p < 0.01), myotube diameter (45.2 ± 6.3 μm vs. 40.1 ± 5.7 μm, p < 0.05), and MyoD (2.1-fold), Myogenin (1.8-fold), and MyHC (2.2-fold). NF-κB and TNF-α were decreased (~0.60-fold and 0.65-fold, respectively), and PGC-1α was increased (1.9-fold). Butyrate docking revealed high binding affinity for AMPK (−6.9 kcal/mol), mTOR (−6.4 kcal/mol), and NF-κB (−6.0 kcal/mol). The performance metrics achieved highly in XGBoost with 88% accuracy. Discussion This comprehensive framework positions probiotics as a precision nutrition intervention for sarcopenia prevention, targeting muscle-sparing effects through microbiome modulation that stimulates coordinated immunometabolic and anabolic actions, with AI-enhanced, individualized risk prediction for healthy aging.