The causal effect between gut microbiota and sarcopenia related traits: A large-scale bidirectional Mendelian randomization

Objective: The causal relationship between gut microbiota and sarcopenia remains unclear. The objective is to investigate the causal association between gut microbiota and sarcopenia related traits, including low hand grip strength (LHGS), appendicular lean mass (ALM), and usual walking speed (UWP), using two-sample Mendelian randomization (MR). Design: Two sample Mendelian randomization study. Setting: and Participants Genetic instruments predicting gut microbiota were from an existing genome-wide association study (GWAS) in 18,340 individuals (85% European descent). Summary data for LHGS (254,894 individuals), ALM ((487,378 individuals), and UWP (335,288 individuals) were respectively from different GWAS. Methods: We selected genetic variants as instrumental variables for 211 taxa at different taxonomic levels and performed inverse variance weighting (IVW) to estimate the causal effects. We also conducted sensitivity analyses including heterogeneity and horizontal pleiotropy. Results: We identified 7, 7, and 10 genetically predicted taxa that showed causal associations with LHGS, ALM, and UWP, respectively. Of these, family Alcaligenaceae, family Family XIII, family Streptococcaceae, genus Eubacterium brachy group, and genus Terrisporobacter were found to be genetically related to LHGS, family Bacteroidaceae, genus Bacteroides, genus Oscillospira, and genus Turicibacter are genetically associated with ALM, and family Veillonellaceae, genus Flavonifractor, genus Lachnospiraceae NC2004 group, genus Ruminococcaceae UCG010, and genus Actinomyces exhibited a genetic correlation with UWP. Sensitivity analysis shows that the above results do not violate the MR assumptions. Conclusion: Our study provides novel evidence for the causal role of gut microbiota in sarcopenia. Modulating the gut microbiota may have potential implications for the prevention and treatment of sarcopenia.