Diabetic retinopathy (DR) is one of leading causes of vision loss in adults with increasing prevalence worldwide. Increasing evidence has emphasized the importance of gut microbiome in the aetiology and development of DR. However, the causal relationship between gut microbes and DR remains largely unknown. To investigate the causal associations of DR with gut microbes and DR risk factors, we employed two‐sample Mendelian Randomization (MR) analyses to estimate the causal effects of 207 gut microbes on DR outcomes. Inputs for MR included Genome‐wide Association Study (GWAS) summary statistics of 207 taxa of gut microbes (the Dutch Microbiome Project) and 21 risk factors for DR. The GWAS summary statistics data of DR was from the FinnGen Research Project. Data analysis was performed in May 2023. We identified eight bacterial taxa that exhibited significant causal associations with DR (FDR < 0.05). Among them, genus Collinsella and species Collinsella aerofaciens were associated with increased risk of DR, while the species Bacteroides faecis, Burkholderiales bacterium_1_1_47, Ruminococcus torques, Streptococcus salivarius, genus Burkholderiales_noname and family Burkholderiales_noname showed protective effects against DR. Notably, we found that the causal effect of species Streptococcus salivarius on DR was mediated through the level of host fasting glucose, a well‐established risk factor for DR. Our results reveal that specific gut microbes may be causally linked to DR via mediating host metabolic risk factors, highlighting potential novel therapeutic or preventive targets for DR.

中文翻译：

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孟德尔随机分析揭示唾液链球菌通过调节宿主空腹血糖对糖尿病视网膜病变的因果影响

糖尿病视网膜病变 (DR) 是成人视力丧失的主要原因之一，其患病率在全球范围内不断增加。越来越多的证据强调肠道微生物组在 DR 的病因和发展中的重要性。然而，肠道微生物与 DR 之间的因果关系仍然很大程度上未知。为了调查 DR 与肠道微生物和 DR 危险因素的因果关系，我们采用双样本孟德尔随机化 (MR) 分析来估计 207 种肠道微生物对 DR 结果的因果影响。 MR 的输入包括 207 个肠道微生物分类群（荷兰微生物组项目）的全基因组关联研究 (GWAS) 汇总统计数据和 21 个 DR 风险因素。 DR的GWAS汇总统计数据来自FinnGen研究项目。数据分析于 2023 年 5 月进行。我们确定了 8 个与 DR 表现出显着因果关系的细菌类群 (FDR < 0.05)。其中，属柯林斯拉和物种产气柯林斯菌与 DR 风险增加相关，而物种粪类杆菌,伯克氏菌属细菌_1_1_47,扭瘤胃球菌、唾液链球菌, 属伯克霍尔德氏菌目和家人伯克霍尔德氏菌目显示出对 DR 的保护作用。值得注意的是，我们发现物种的因果效应唾液链球菌对 DR 的影响是通过宿主空腹血糖水平介导的，空腹血糖水平是 DR 的一个公认的危险因素。我们的研究结果表明，特定的肠道微生物可能通过介导宿主代谢危险因素与 DR 存在因果关系，突出了 DR 的潜在新治疗或预防靶点。