Abstract
BACKGROUND/OBJECTIVE: Prolonged bed rest is highly prevalent among hospitalized older adults and markedly accelerates the loss of muscle mass and physical function. Currently, there are no effective interventions to counteract this decline, and the underlying mechanisms remain poorly characterized. This study aimed to investigate whether high protein intake can simultaneously modulate muscle mass and the gut microbiota, and whether gut microbial composition mediates muscle regulation in hospitalized older people. METHODS: A self-controlled study was conducted on 43 older patients aged 60 to 90 years old with low skeletal muscle mass. During the 3-month intervention phase, all participants received approximately 36 g of high-protein supplementation daily, comprising both casein and whey proteins. This was followed by a 3-month control phase in which participants received standard nursing care without protein supplementation. RESULTS: A significant increase in skeletal muscle mass index from baseline was seen in male group at 3 months (6.0-6.3 kg/m(2)) but declined to 6.1 kg/m(2) at 6 months (P < 0.05). No significant changes were observed in females (P > 0.05). Gut microbiota analysis revealed that bacterial diversity and microbial structure were affected by protein supplementation and differed by sex. Males exhibited a greater abundance of SMI- and SMM-associated beneficial bacteria following protein intake. Furthermore, metabolic pathway analysis indicated that microbial functions related to amino acid synthesis were positively correlated with SMI-linked species such as Blautia wexlerae and Corynebacterium dentalis. CONCLUSIONS: High-protein supplementation may promote muscle anabolism in hospitalized older males by modulating the composition and metabolic function of the gut microbiota, specifically by enhancing microbial pathways related to amino acid synthesis. These results suggest the presence of a gut-muscle axis and highlight the potential of targeted protein interventions to counteract inactivity-related muscle loss in older patients. TRIAL REGISTRATION: The trial was registered at Chinese Clinical Trial Registry with identifier ChiCTR2400085432 on 07/06/2024.