Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, China.
National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.
J Gerontol A Biol Sci Med Sci. 2024 Sep 1;79(9). doi: 10.1093/gerona/glae173.
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.
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.
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.
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.
肠道微生物群落失衡和肌肉减少症在老年人中经常观察到。肠道微生物群落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，但这些关联是否具有因果关系尚不清楚。
我们使用连锁不平衡得分回归和双样本 Mendelian 随机化（MR）方法，使用源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，来研究肠道微生物群落及其代谢物与肌肉减少症之间的因果关系。在进行 MR 分析后，我们进行了后续的敏感性分析，以加强获得结果的稳健性和可信度。
MR 分析提供了有力的证据，表明遗传预测的肠道微生物群落和代谢物与肌肉减少症的风险之间存在相关性。厚壁菌门、理研菌科、瘤胃球菌科和 Victivallis 的丰度与步行速度有关。我们的研究还发现了 12 种肠道细菌与四肢瘦体重之间的关联，以及链球菌科、Intestinibacter、Paraprevotella、瘤胃球菌科 UCG009 和 Sutterella 与握力之间的关联。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落衍生代谢物。
利用双样本 MR 方法，我们的研究阐明了肠道微生物群落、肠道微生物群落衍生代谢物与肌肉减少症之间的因果关系。这些发现表明，肠道微生物群落和代谢物可能是肌肉减少症的潜在潜在风险因素，并为新的治疗靶点提供了希望。
