Xiong Yujun, Zhu Xingyun, Xu Huazhao, Zheng Zitian, Luo Qingfeng
Department of Gastroenterology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine Chinese Academy of Medical Sciences Beijing China.
Department of Endocrinology Beijing Jishuitan Hospital Beijing People's Republic of China.
Aging Med (Milton). 2025 Feb 18;8(1):e70009. doi: 10.1002/agm2.70009. eCollection 2025 Feb.
Diabetic nephropathy (DN) is a severe complication of diabetes mellitus, and its pathogenesis remains incompletely understood. Emerging evidence suggests a potential link between gut microbiota and DN. This study aimed to explore the causal relationship between gut microbiota and DN using a two-sample Mendelian randomization (MR) approach.
Gut microbiota data were obtained from the MiBioGen consortium, which provides the most comprehensive genome-wide association studies (GWAS) on gut microbiota. Summary-level genetic data for DN were sourced from publicly available GWAS data provided by the FinnGen consortium. The primary analysis was conducted using the inverse variance-weighted (IVW) method, complemented by sensitivity analyses to evaluate pleiotropy and heterogeneity.
Fourteen gut microbiota species demonstrated significant genetic associations with DN in the MR analysis, including five negatively and nine positively associated species, as determined by the IVW method. No evidence of pleiotropy or heterogeneity was observed, ensuring the robustness of the findings.
This study provides novel insight into the causal role of gut microbiota in DN pathogenesis, uncovering specific microbial species that may contribute to disease progression. These findings offer a promising avenue for future research and therapeutic development targeting gut microbiota.
糖尿病肾病（DN）是糖尿病的一种严重并发症，其发病机制尚未完全明确。新出现的证据表明肠道微生物群与DN之间可能存在联系。本研究旨在使用两样本孟德尔随机化（MR）方法探讨肠道微生物群与DN之间的因果关系。
肠道微生物群数据来自MiBioGen联盟，该联盟提供了关于肠道微生物群最全面的全基因组关联研究（GWAS）。DN的汇总水平遗传数据来自FinnGen联盟提供的公开可用GWAS数据。主要分析采用逆方差加权（IVW）方法，并辅以敏感性分析以评估多效性和异质性。
在MR分析中，14种肠道微生物物种与DN表现出显著的遗传关联，其中5种呈负相关，9种呈正相关，这是通过IVW方法确定的。未观察到多效性或异质性的证据，确保了研究结果的稳健性。
本研究为肠道微生物群在DN发病机制中的因果作用提供了新的见解，发现了可能导致疾病进展的特定微生物物种。这些发现为未来针对肠道微生物群的研究和治疗开发提供了有希望的途径。
