Background Gut microbiota imbalance and sarcopenia are frequently observed in older adults. 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 2-sample Mendelian randomization (MR) methods with single-nucleotide polymorphisms 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 walking pace. Our study also found suggestive associations of 12 intestinal bacteria with appendicular lean mass, and of Streptococcaceae, Intestinibacter, Paraprevotella, Ruminococcaceae UCG009, and Sutterella with grip strength. Specifically, we identified 21 gut microbiota-derived metabolites that may be associated with the risk of sarcopenia. Conclusions Utilizing a 2-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.

中文翻译：

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肠道微生物群、代谢物和肌肉减少症之间的因果关系：一项孟德尔随机化研究


背景 肠道菌群失衡和肌肉减少症经常在老年人中观察到。肠道微生物群及其代谢物被认为是导致肌肉减少症风险增加的危险因素，但这些关联是否是因果关系尚不清楚。方法 我们进行了连锁不平衡评分回归和 2 样本孟德尔随机化 （MR） 方法，以来自大规模全基因组关联研究的单核苷酸多态性作为工具变量，以检查肠道微生物群与其代谢物与肌肉减少症之间的因果关系。在 MR 分析之后，进行了后续的敏感性分析，以加强所获结果的稳健性和可信度。结果 MR 分析产生了令人信服的证据，证明了基因预测的肠道微生物群和代谢物与肌肉减少症风险之间的相关性。发现 Porphyromonadaceae 、 Rikenellaceae 、 Terrisporobacter 和 Victivallis 的丰度与步行速度有关。我们的研究还发现 12 种肠道细菌与附肢瘦块有关，链球菌科、肠杆菌属、副普雷沃菌属、瘤胃球菌科 UCG009 和萨特氏菌属与握力有关。具体来说，我们确定了 21 种可能与肌肉减少症风险相关的肠道微生物群衍生代谢物。结论 利用 2 样本 MR 方法，我们的研究阐明了肠道微生物群、肠道微生物群衍生代谢物和肌肉减少症发生之间的因果相互作用。这些发现表明，肠道微生物群和代谢物可能代表了肌肉减少症的潜在潜在危险因素，并有望成为新的治疗重点。