Chen Kai, Wang Xu, Shang Zhihao, Li Qingyue, Yao Wenqiang, Guo Shaobo, Guan Yingting
The First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, China.
Jiangsu Province Hospital of Chinese Medicine, Nanjing, China.
Comb Chem High Throughput Screen. 2025;28(6):1026-1038. doi: 10.2174/0113862073311197240425073859.
In recent years, an increasing number of studies have indicated a bidirectional relationship between gut microbiota and the kidneys (the gut-kidney axis). Currently, the potential causal relationship between gut microbiota and diabetic nephropathy remains unclear. This study explores the causal effects of gut microbiota on diabetic nephropathy through Mendelian randomization.
We carried out a comprehensive Mendelian Randomization (MR) analysis, drawing on the Genome-wide Association Study (GWAS) data for 196 varieties of gut microbiota and diabetic nephropathy. The primary analytical approach employed was the inverse-variance weighted, supplemented by the MR-Egger, weighted median, simple mode, and weighted mode. We rigorously assessed heterogeneity with Cochran's Q test and examined pleiotropy via MREgger intercept and MR-PRESSO tests. To ensure the reliability of our findings, we conducted funnel plots and leave-one-out analysis.
Our study indicates a causal relationship between the increased risk of diabetic nephropathy and specific gut microbiota, including the (P=0.01892; OR=1.593; 95%CI, 1.080-2.350), (P=0.01892; OR=1.593; 95% CI, 1.080-2.350), and (P=0.01350; OR=1.452; 95% CI, 1.080-1.953). Conversely, potential protective factors include the (P=0.00397; OR=0.528; 95% CI, 0.342-0.815), (P=0.00965; OR=0.474; 95% CI, 0.270-0.834), (P=0.04417; OR=0.756; 95% CI, 0.576-0.993), (P=0.04417; OR=0.756; 95% CI, 0.576-0.993), and (P=0.00118; OR=0.513; 95%CI, 0.343-0.768).
This study confirms the causal effects of gut microbiota on diabetic nephropathy. Identifying the risk and protective factors within the gut microbiota for diabetic nephropathy offers fresh insights and novel approaches for preventing and treating this condition.
近年来，越来越多的研究表明肠道微生物群与肾脏之间存在双向关系（肠-肾轴）。目前，肠道微生物群与糖尿病肾病之间的潜在因果关系仍不明确。本研究通过孟德尔随机化探讨肠道微生物群对糖尿病肾病的因果效应。
我们利用196种肠道微生物群和糖尿病肾病的全基因组关联研究（GWAS）数据进行了全面的孟德尔随机化（MR）分析。采用的主要分析方法是逆方差加权，并辅以MR-Egger、加权中位数、简单模式和加权模式。我们用Cochran's Q检验严格评估异质性，并通过MREgger截距和MR-PRESSO检验检查多效性。为确保研究结果的可靠性，我们进行了漏斗图分析和留一法分析。
我们的研究表明糖尿病肾病风险增加与特定肠道微生物群之间存在因果关系，包括（P=0.01892；OR=1.593；95%CI，1.080-2.350）、（P=0.01892；OR=1.593；95%CI，1.080-2.350）和（P=0.01350；OR=1.452；95%CI，1.080-1.953）。相反，潜在的保护因素包括（P=0.00397；OR=0.528；95%CI，0.342-0.815）、（P=0.00965；OR=0.474；95%CI，0.270-0.834）、（P=0.04417；OR=0.756；95%CI，0.576-0.993）、（P=0.04417；OR=0.756；95%CI，0.576-0.993）和（P=0.00118；OR=0.513；95%CI，0.343-0.768）。
本研究证实了肠道微生物群对糖尿病肾病的因果效应。确定肠道微生物群中糖尿病肾病的风险和保护因素为预防和治疗该疾病提供了新的见解和方法。
