关键词: Mendelian randomization causality elderly people frailty gut microbiota

来  源:   DOI:10.3389/fmed.2024.1354037   PDF(Pubmed)

Abstract:
UNASSIGNED: Frailty is a complex geriatric syndrome that seriously affects the quality of life of older adults. Previous observational studies have reported a strong relationship of frailty with the gut microbiota; however, further studies are warranted to establish a causal link. Accordingly, we aimed to conduct a bidirectional Mendelian randomization study to assess the causal relationship between frailty, as measured by the frailty index, and gut microbiota composition.
UNASSIGNED: Instrumental variables for the frailty index (N = 175, 226) and 211 gut bacteria (N = 18,340) were obtained through a genome-wide association study. A two-sample Mendelian randomization analysis was performed to assess the causal relationship of gut microbiota with frailty. Additionally, we performed inverse Mendelian randomization analyses to examine the direction of causality. Inverse variance weighting was used as the primary method in this study, which was supplemented by horizontal pleiotropy and sensitivity analyses to increase confidence in the results.
UNASSIGNED: Bacteroidia (b = -0.041, SE = 0.017, p = 0.014) and Eubacterium ruminantium (b = -0.027, SE = 0.012, p = 0.028) were protective against frailty amelioration. Additionally, the following five bacteria types were associated with high frailty: Betaproteobacteria (b = 0.049, SE = 0.024, p = 0.042), Bifidobacterium (b = 0.042, SE = 0.016, p = 0.013), Clostridium innocuum (b = 0.023, SE = 0.011, p = 0.036), E. coprostanoligenes (b = 0.054, SE = 0.018, p = 0.003), and Allisonella (b = 0.032, SE = 0.013, p = 0.012). Contrastingly, frailty affected Butyrivibrio in the gut microbiota (b = 1.225, SE = 0.570, p = 0.031). The results remained stable within sensitivity and validation analyses.
UNASSIGNED: Our findings strengthen the evidence of a bidirectional causal link between the gut microbiota and frailty. It is important to elucidate this relationship to optimally enhance the care of older adults and improve their quality of life.
摘要:
虚弱是一种复杂的老年综合征,严重影响老年人的生活质量。以前的观察性研究报道了虚弱与肠道微生物群之间的强烈关系;然而,需要进一步的研究来建立因果关系.因此,我们的目的是进行双向孟德尔随机研究,以评估之间的因果关系脆弱,以脆弱指数衡量,和肠道菌群组成。
通过全基因组关联研究获得了脆弱指数(N=175,226)和211个肠道细菌(N=18,340)的工具变量。进行了双样本孟德尔随机化分析,以评估肠道微生物群与脆弱的因果关系。此外,我们进行了反向孟德尔随机化分析以检验因果关系的方向.在这项研究中,方差反加权被用作主要方法,并辅以水平多效性和敏感性分析,以提高结果的可信度。
拟杆菌(b=-0.041,SE=0.017,p=0.014)和反刍动物(b=-0.027,SE=0.012,p=0.028)对脆弱的改善具有保护作用。此外,以下五种细菌类型与高度脆弱相关:变形杆菌(b=0.049,SE=0.024,p=0.042),双歧杆菌(b=0.042,SE=0.016,p=0.013),梭菌感染(b=0.023,SE=0.011,p=0.036),E.共生前列腺素(b=0.054,SE=0.018,p=0.003),和Allisonella(b=0.032,SE=0.013,p=0.012)。相反,衰弱影响肠道微生物群中的Butyrivibrio(b=1.225,SE=0.570,p=0.031)。结果在灵敏度和验证分析中保持稳定。
我们的发现加强了肠道微生物群和脆弱之间双向因果联系的证据。重要的是阐明这种关系,以最佳地增强老年人的护理并改善他们的生活质量。
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