■先前的观察性研究表明肠道菌群与糖尿病神经病变(DN)之间存在关联。然而,混杂因素和反向因果关系使得肠道菌群与DN之间的因果关系不确定。我们旨在研究肠道菌群丰度与DN之间的相互作用因果关系。
■我们进行了孟德尔随机化(MR)分析,以检查肠道微生物群与DN之间的因果关系。从MiBioGen联盟获得了属水平的肠道微生物群的基因组数据,包括18,340名欧洲血统的人。糖尿病性多发性神经病(DPN)的数据来自FinnGen联盟,其中包括1,048例病例和374,434例对照,虽然糖尿病自主神经病变(DAN)的数据也从FinnGen联盟获得,包括111例病例和374,434例对照。因果关系主要使用逆方差加权(IVW)分析来估计,补充了四种验证方法,以及额外的敏感性分析来评估多效性,异质性,工具变量的稳健性。
■IVW分析表明,普雷沃氏菌9对DPN具有保护作用(OR=0.715,95%CI:0.521-0.982,P=0.038),拟杆菌也具有保护作用(OR=0.602,95%CI:0.364-0.996,P=0.048)。另一方面,反刍球球菌2型对DPN有促进作用(OR=1.449,95%CI:1.008~2.083,P=0.045)。布劳特(OR=0.161,95%CI:0.035-0.733,P=0.018),梭菌感染组(OR=3.033,95%CI:1.379-6.672,P=0.006),和Howardella(OR=2.595,95%CI:1.074-6.269,P=0.034)在IVW分析中与DAN有因果关系,没有异质性或多效性的证据。敏感性分析显示没有明显的多效性或异质性。
■我们的研究确定了肠道菌群与糖尿病性神经病变风险增加或降低之间的因果关系。这些发现强调了在糖尿病神经病变的管理中采用将肠道微生物群调节与其他治疗干预相结合的综合方法的重要性。
UNASSIGNED: Previous observational studies have suggested an association between gut microbiota and diabetic neuropathy (DN). However, confounding factors and reverse causality make the causal relationship between gut microbiota and DN uncertain. We aimed to investigate the interactive causal relationships between the abundance of gut microbiota and DN.
UNASSIGNED: We conducted a Mendelian randomization (MR) analysis to examine the causal relationship between gut microbiota and DN. Genomic data on gut microbiota at the genus level were obtained from the MiBioGen Consortium, including 18,340 individuals of European descent. Data on diabetic polyneuropathy (DPN) were obtained from the FinnGen Consortium, which included 1,048 cases and 374,434 controls, while data on diabetic autonomic neuropathy (DAN) were also obtained from the FinnGen Consortium, including 111 cases and 374,434 controls. Causal effects were primarily estimated using inverse variance weighted (IVW) analysis, supplemented with four validation methods, and additional sensitivity analyses to assess the pleiotropy, heterogeneity, and robustness of instrumental variables.
UNASSIGNED: The IVW analysis indicated that
Prevotella 9 had a protective effect on DPN (OR = 0.715, 95% CI: 0.521-0.982, P = 0.038), and Bacteroides also showed a protective effect (OR = 0.602, 95% CI: 0.364-0.996, P = 0.048). On the other hand, Ruminococcus 2 had a promoting effect on DPN (OR = 1.449, 95% CI: 1.008-2.083, P = 0.045). Blautia (OR = 0.161, 95% CI: 0.035-0.733, P = 0.018), Clostridium innocuum group (OR = 3.033, 95% CI: 1.379-6.672, P = 0.006), and Howardella (OR = 2.595, 95% CI: 1.074-6.269, P = 0.034) were causally associated with DAN in the IVW analysis, with no evidence of heterogeneity or pleiotropy. Sensitivity analyses showed no significant pleiotropy or heterogeneity.
UNASSIGNED: Our study identified a causal relationship between gut microbiota and the increased or decreased risk of diabetic neuropathy. These findings underscore the importance of adopting a comprehensive approach that combines gut microbiota modulation with other therapeutic interventions in the management of diabetic neuropathy.