PDF(Pubmed)
Abstract：
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.
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.
摘要：
背景：老年人群中经常观察到肠道菌群失衡和肌肉减少症。肠道菌群及其代谢产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双样本孟德尔随机化方法，使用来自大规模全基因组关联研究的SNP作为工具变量，以检查将肠道微生物群及其代谢产物与肌肉减少症之间的因果关系。在MR分析之后，随后进行了敏感性分析,以增强所得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。卟啉科的丰富，Rikenellaceae，Terrisporibacter,并且Victivallis被发现与WP有关。我们的研究还发现了12种肠道细菌与ALM的暗示性关联，和链球菌科，肠杆菌,Paraprevotella,RuminococycaceaeUCG009，和带有GS的梭菌。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菌群代谢产物.
结论：利用双样本MR方法，我们的研究阐明了肠道微生物群之间的因果关系，肠道微生物来源的代谢产物，以及肌少症的发生。这些研究结果表明，肠道菌群和代谢产物可能是肌肉减少症的潜在潜在危险因素。并提供新的治疗焦点的承诺。
方法：我们进行了连锁不平衡评分回归和双样本孟德尔随机化方法，使用来自大规模全基因组关联研究的SNP作为工具变量，以检查将肠道微生物群及其代谢产物与肌肉减少症之间的因果关系。在MR分析之后，随后进行了敏感性分析,以增强所得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。卟啉科的丰富，Rikenellaceae，Terrisporibacter,并且Victivallis被发现与WP有关。我们的研究还发现了12种肠道细菌与ALM的暗示性关联，和链球菌科，肠杆菌,Paraprevotella,RuminococycaceaeUCG009，和带有GS的梭菌。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菌群代谢产物.
结论：利用双样本MR方法，我们的研究阐明了肠道微生物群之间的因果关系，肠道微生物来源的代谢产物，以及肌少症的发生。这些研究结果表明，肠道菌群和代谢产物可能是肌肉减少症的潜在潜在危险因素。并提供新的治疗焦点的承诺。
