Investigating association between gut microbiota and sarcopenia-related traits:a Mendelian randomization study

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.