Abstract
BACKGROUND: Observational studies have indicated a potential link between gut microbiota and sarcopenia. However, the underlying mechanisms and a causal relationship have not been established. Thus, the objective of this study is to examine the possible causal association between gut microbiota and sarcopenia-related traits, including low hand-grip strength and appendicular lean mass (ALM), to shed light on the gut-muscle axis. METHODS: To investigate the potential impact of gut microbiota on low hand-grip strength and ALM, we utilized a two-sample Mendelian randomization (MR) approach. Summary statistics were obtained from genome-wide association studies of gut microbiota, low hand-grip strength, and ALM. The primary MR analysis employed the random-effects inverse-variance weighted (IVW) method. To assess the robustness, we conducted sensitivity analyses using the MR pleiotropy residual sum and outlier (MR-PRESSO) test to detect and correct for horizontal pleiotropy, as well as the MR-Egger intercept test and leave-one-out analysis. RESULTS: Alcaligenaceae, Family XIII, and Paraprevotella were positively associated with the risk of low hand-grip strength (P-values < 0.05). Streptococcaceae were negatively associated with low hand-grip strength (P-values < 0.05). Eight bacterial taxa (Actinomycetales, Actinomycetaceae, Bacteroidaceae, Porphyromonadaceae, Prevotellaceae, Bacteroides, Marvinbryantia, and Phascolarctobacterium) were associated with a higher risk of ALM (P-values < 0.05). Eubacterium fissicatena group was negatively associated with ALM (P-values < 0.05). CONCLUSION: We found several gut microbiota components causally associated with sarcopenia-related traits. Our findings provided insights into novel strategies for the prevention and treatment of sarcopenia through the regulation of the gut microbiota, contributing to a better understanding of the gut-muscle axis.