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探讨肠道微生物群与慢性肾脏病因果关系中的潜在联系:一项两样本孟德尔随机化研究。

Exploring the potential link between gut microbiota and chronic kidney disease in causality: A 2-sample Mendelian randomization study.

机构信息

First Clinical Medical College, Hubei University of Chinese Medicine, Wuhan, Hubei, China.

College of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Pudong New Area, Shanghai, China.

出版信息

Medicine (Baltimore). 2024 Oct 25;103(43):e40236. doi: 10.1097/MD.0000000000040236.

Abstract

Increasing evidence indicates a significant correlation between gut microbiota (GM) and susceptibility to chronic kidney disease (CKD). However, causal relationship presence remains uncertain. Mendelian randomization (MR) was applied to evaluate potential causal relation from GM to CKD. Genomic association analysis aggregates publicly online databases, utilizing Genome-Wide Association Study (GWAS) database focused on GM and CKD. For examination of potential causal connection from GM to CKD, a 2-way, 2-sample Mendelian randomization (MR) method was applied. Sensitivity analyses were utilized to scrutinize for heterogeneity, horizontal pleiotropy, MR outcomes resilience. Result from inverse variance weighting (IVW) method revealed that 10 microbiotas such as Porphyromonadaceae (OR = 1.351, 95% CI: 1.114-1.638, P = .002), Dorea (OR = 1.236, 95% CI: 1.040-1.468, P = .016), Ruminococcus torques group (OR = 1.290, 95% CI: 1.035-1.608, P = .024) are potential CKD risk factors. Five microbiotas, including the Prevotellaceae (OR = 0.814, 95% CI: 0.719-0.922, P = .001) are potential CKD protective factors. Sensitivity analyses reveal no horizontal pleiotropy or heterogeneity. Additionally, reverse MR results unveiled potential relation between CKD and disorders in 3 microbiotas, including Senegalimassilia. According to the investigation, MR method was employed to delve into reciprocal causal connection from GM to CKD. Our findings identified 15 types of GM causally linked to CKD, as well as CKD demonstrating causal associations with 3 types of GM. Further exploration of these associated GM types is hopeful to raise novel insights, for CKD preventing and early monitoring.

摘要

越来越多的证据表明,肠道微生物群(GM)与慢性肾脏病(CKD)的易感性之间存在显著相关性。然而,因果关系的存在仍然不确定。孟德尔随机化(MR)被应用于评估 GM 对 CKD 的潜在因果关系。基因组关联分析汇总了公开的在线数据库,利用 GM 和 CKD 的全基因组关联研究(GWAS)数据库。为了检查 GM 对 CKD 的潜在因果关系,采用了双向、两样本孟德尔随机化(MR)方法。利用敏感性分析来检查异质性、水平多效性、MR 结果的稳健性。逆方差加权(IVW)方法的结果表明,10 种微生物群,如卟啉单胞菌科(OR=1.351,95%CI:1.114-1.638,P=0.002)、Dorea(OR=1.236,95%CI:1.040-1.468,P=0.016)、瘤胃球菌组(OR=1.290,95%CI:1.035-1.608,P=0.024)是潜在的 CKD 风险因素。5 种微生物群,包括普雷沃氏菌科(OR=0.814,95%CI:0.719-0.922,P=0.001)是潜在的 CKD 保护因素。敏感性分析显示没有水平多效性或异质性。此外,反向 MR 结果揭示了 CKD 与 3 种微生物群中的疾病之间的潜在关系,包括塞内加尔伊米西亚利。根据调查结果,MR 方法被用于深入研究 GM 对 CKD 的相互因果关系。我们的研究结果确定了 15 种与 CKD 有因果关系的 GM 类型,以及 CKD 与 3 种 GM 之间存在因果关系。进一步探索这些相关的 GM 类型有望为 CKD 的预防和早期监测提供新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2fee/11521073/266b6f88db48/medi-103-e40236-g001.jpg

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