Table_2_Association between gut microbiota and diabetic nephropathy: a two-sample Mendelian randomization study.xlsx

BackgroundTo clarify the causal relationship between gut microbiota and diabetic nephropathy (DN), we employed Mendelian randomization (MR). Despite a strong correlation observed, establishing causality is still unclear. By utilizing MR, we aimed to investigate this relationship further and shed light on the potential causal effect of gut microbiota on DN.
MethodsGenetic instrumental variables for gut microbiota were obtained from a GWAS with 18340 participants. DN summary statistics (1032 cases, 451248 controls) were sourced from a separate GWAS. The primary analysis used the inverse-variance weighted (IVW) method. Reverse MR analysis was conducted to explore reverse causation. Rigorous sensitivity analyses were performed to ensure the resilience and reliability of the study’s findings.
ResultsWe found two bacterial traits associated with an increased risk of DN: genus LachnospiraceaeUCG008 (OR: 1.4210; 95% CI: 1.0450, 1.9322; p = 0.0250) and genus Terrisporobacter (OR: 1.9716; 95% CI: 1.2040, 3.2285; p = 0.0070). Additionally, phylum Proteobacteria (OR: 0.4394; 95% CI: 0.2721, 0.7096; p = 0.0008) and genus Dialister (OR: 0.4841; 95% CI: 0.3171, 0.7390; p = 0.0008) were protective against DN. Sensitivity analyses consistently supported these results. In the reverse MR analysis, no statistically significant associations were observed between DN and these four bacterial traits.
ConclusionsOur analyses confirmed a potential causal relationship between certain gut microbiota taxa and the risk of DN. However, additional studies are required to elucidate the underlying mechanisms through which gut microbiota influences the development of DN.

【背景】为明确肠道菌群与糖尿病肾病（diabetic nephropathy, DN）之间的因果关联，本研究采用孟德尔随机化（Mendelian randomization, MR）方法。尽管已有研究观察到二者存在较强相关性，但因果关系的确定仍不明确。本研究借助MR方法进一步探究二者的关联，以期阐明肠道菌群对糖尿病肾病的潜在因果效应。
【方法】肠道菌群的遗传工具变量源自一项纳入18340名参与者的全基因组关联研究（Genome-Wide Association Study, GWAS）。糖尿病肾病的汇总统计数据（1032例病例，451248例对照）来自另一项独立的GWAS。本研究的主要分析采用逆方差加权（inverse-variance weighted, IVW）法。此外开展反向MR分析以探究反向因果关联。同时进行了严格的敏感性分析，以保障研究结果的稳健性与可靠性。
【结果】本研究发现两种细菌类群与糖尿病肾病的发病风险升高相关：毛螺菌科UCG008属（genus LachnospiraceaeUCG008，比值比（odds ratio, OR）=1.4210；95%置信区间（confidence interval, CI）：1.0450~1.9322；P=0.0250）以及泰里孢杆菌属（genus Terrisporobacter，OR=1.9716；95%CI：1.2040~3.2285；P=0.0070）。此外，变形菌门（phylum Proteobacteria，OR=0.4394；95%CI：0.2721~0.7096；P=0.0008）和二嗜菌属（genus Dialister，OR=0.4841；95%CI：0.3171~0.7390；P=0.0008）对糖尿病肾病具有保护作用。敏感性分析结果与上述发现一致。反向MR分析未观察到糖尿病肾病与这四种细菌类群之间存在统计学显著的关联。
【结论】本研究证实了特定肠道菌群类群与糖尿病肾病发病风险之间存在潜在因果关联。但仍需开展更多研究以阐明肠道菌群影响糖尿病肾病发生发展的具体分子机制。