Causal Relationship Between Gut Microbiota, Metabolites, and Sarcopenia: A Mendelian Randomization Study

Abstract

Background Gut microbiota imbalance and sarcopenia are frequently observed in the elderly population. Gut Microbiota and their metabolites are considered risk factors contributing to the heightened risk of sarcopenia, but whether these associations are causal remains unclear. Methods We conducted linkage disequilibrium score regression and two-sample Mendelian randomization methods with SNPs sourced from large-scale genome-wide association studies as instrumental variables to examine the causal associations linking gut microbiota with their metabolites to the sarcopenia. Following the MR analysis, subsequent sensitivity analyses were conducted to reinforce the robustness and credibility of the obtained results. Results MR analysis yielded compelling evidence demonstrating the correlation between genetically predicted gut microbiota and metabolites and the risk of sarcopenia. The abundance of Porphyromonadaceae, Rikenellaceae, Terrisporobacter, and Victivallis was found to be associated with WP. Our study also found suggestive associations of 12 intestinal bacteria with ALM, and of Streptococcaceae, Intestinibacter, Paraprevotella, Ruminococcaceae UCG009, and Sutterella with GS. Specifically, we identified 21 gut microbiota-derived metabolites that may be associated with the risk of sarcopenia. Conclusions Utilizing a two-sample MR approach, our study elucidates the causal interplay among gut microbiota, gut microbiota-derived metabolites, and the occurrence of sarcopenia. These findings suggest that gut microbiota and metabolites may represent a potential underlying risk factor for sarcopenia, and offer the promise of novel therapeutic focal points.