■观察性研究和一些实验研究表明,肠道菌群与慢性肾衰竭的发生和进展密切相关。然而,肠道菌群与慢性肾衰竭之间的因果关系尚不清楚.本研究采用双样本孟德尔随机化方法在遗传水平上推断肠道微生物群与慢性肾衰竭之间的因果关系。这项研究旨在确定肠道微生物群是否对慢性肾衰竭的风险有因果关系。旨在为慢性肾功能衰竭的靶向治疗提供新的证据支持。
■使用来自公共MiBioGen和IEUOpenGWAS平台的全基因组关联研究(GWAS)数据,我们进行了双样本孟德尔随机化分析.使用五种不同的方法推断肠道微生物群和慢性肾衰竭之间的因果关系:反向方差加权,MR-Egger,加权中位数,简单模式,和加权模式。该研究纳入了包括多效性和异质性评估的敏感性分析。随后,孟德尔随机化分析的结果对多重检验进行了严格的校正,采用错误发现率方法来提高我们发现的有效性。
■根据逆方差加权法的结果,7个细菌属显示与结果变量慢性肾衰竭显著相关.其中,Ruminococus(gauvreaii组)(OR=0.82,95%CI=0.71-0.94,p=0.004)可能是慢性肾衰竭的保护因素,而埃希氏杆菌属(OR=1.22,95%CI=1.08-1.38,p=0.001),乳球菌(OR=1.1,95%CI=1.02-1.19,p=0.013),Odoribacter(OR=1.23,95%CI=1.03-1.49,p=0.026),肠位(OR=1.14,95%CI=1.00-1.29,p=0.047),真细菌(eligens组)(OR=1.18,95%CI=1.02-1.37,p=0.024),Howardella(OR=1.18,95%CI=1.09-1.28,p<0.001)可能是慢性肾功能衰竭的危险因素。然而,在使用错误发现率对多重比较进行校正后,只有与大肠杆菌-志贺氏菌和Howardella的关联仍然显着,表明其他属具有暗示性关联。敏感性分析未显示任何多效性或异质性。
■我们的孟德尔随机双样本研究表明,埃希氏菌属-志贺氏菌属和霍华德氏菌属是慢性肾衰竭的危险因素,它们可以作为未来治疗干预的潜在目标。然而,确切的作用机制尚不清楚,需要进一步研究以充分阐明其确切作用。
UNASSIGNED: Observational studies and some experimental investigations have indicated that gut microbiota are closely associated with the incidence and progression of chronic renal failure. However, the causal relationship between gut microbiota and chronic renal failure remains unclear. The present
study employs a two-sample Mendelian randomization approach to infer the causal relationship between gut microbiota and chronic renal failure at the genetic level. This research aims to determine whether there is a causal effect of gut microbiota on the risk of chronic renal failure, aiming to provide new evidence to support targeted gut therapy for the treatment of chronic renal failure.
UNASSIGNED: Employing genome-wide association
study (GWAS) data from the public MiBioGen and IEU OpenGWAS platform, a two-sample Mendelian randomization analysis was conducted. The causal relationship between gut microbiota and chronic renal failure was inferred using five different methods: Inverse Variance Weighted, MR-Egger, Weighted Median, Simple Mode, and Weighted Mode. The
study incorporated sensitivity analyses that encompassed evaluations for pleiotropy and heterogeneity. Subsequently, the results of the Mendelian randomization analysis underwent a stringent correction for multiple testing, employing the False Discovery Rate method to enhance the validity of our findings.
UNASSIGNED: According to the results from the Inverse Variance Weighted method, seven bacterial genera show a significant association with the outcome variable chronic renal failure. Of these, Ruminococcus (gauvreauii group) (OR = 0.82, 95% CI = 0.71-0.94, p = 0.004) may act as a protective factor against chronic renal failure, while the genera Escherichia-Shigella (OR = 1.22, 95% CI = 1.08-1.38, p = 0.001), Lactococcus (OR = 1.1, 95% CI = 1.02-1.19, p = 0.013), Odoribacter (OR = 1.23, 95% CI = 1.03-1.49, p = 0.026), Enterorhabdus (OR = 1.14, 95% CI = 1.00-1.29, p = 0.047), Eubacterium (eligens group) (OR = 1.18, 95% CI = 1.02-1.37, p = 0.024), and Howardella (OR = 1.18, 95% CI = 1.09-1.28, p < 0.001) may be risk factors for chronic renal failure. However, after correction for multiple comparisons using False Discovery Rate, only the associations with Escherichia-Shigella and Howardella remain significant, indicating that the other genera have suggestive associations. Sensitivity analyses did not reveal any pleiotropy or heterogeneity.
UNASSIGNED: Our two-sample Mendelian randomization
study suggests that the genera Escherichia-Shigella and Howardella are risk factors for chronic renal failure, and they may serve as potential targets for future therapeutic interventions. However, the exact mechanisms of action are not yet clear, necessitating further research to elucidate their precise roles fully.