■人体内的肠道菌群(GM)稳态与健康密切相关,可用作预防疾病发作和进展的调节剂。糖尿病微血管并发症不仅给社会带来巨大的经济负担,但也有痛苦的精神和身体上的痛苦。因此,改变GM可能是延缓糖尿病微血管并发症的一种方法。
■进行了两个样本的孟德尔随机化(MR)分析,以揭示GM与三个核心糖尿病微血管并发症之间的因果关系,即,糖尿病肾病(DKD),糖尿病视网膜病变(DR),和糖尿病神经病变(DNP)。
■首先,对来自MiBioGen联盟的GM的全基因组关联研究(GWAS)汇总统计数据和从FinnGen研究项目获得的三种主要糖尿病微血管并发症进行了评估.第二,进行了正向MR分析,以评估GM对DKD风险的因果关系,DR,DNP。第三,一系列的敏感性研究,比如异质性测试,多效性评估,和遗漏分析,进一步评估MR分析的准确性。最后,进行了Steiger测试和反向MR分析,以评估反向因果关系的可能性。
■总共选择了2,092个与196个细菌性状相关的单核苷酸多态性作为工具变量。这个两个样本的MR分析提供了强有力的合理证据,表明28个基因预测的特定GM的丰度在DKD的发生中起不可忽视的作用,DR,DNP并发症与23GM有因果关系,比值比通常在0.9到1.1之间。进一步的敏感性分析表明异质性低,多效性低,因果估计的高可靠性。
■该研究提出了GM可能是预防和延缓糖尿病微血管并发症进展的潜在目标的可能性。有必要对GM治疗糖尿病微血管并发症进行进一步的实验,以阐明其作用和具体机制。
UNASSIGNED: Gut microbiota (GM) homeostasis in the human body is closely associated with health, which can be used as a regulator for preventing the onset and progression of disease. Diabetic microvascular complications bring about not only a huge economic burden to society, but also miserable mental and physical pain. Thus, alteration of the GM may be a method to delay diabetic microvascular complications.
UNASSIGNED: A two-sample Mendelian randomization (MR) analysis was conducted to reveal the causal inference between GM and three core diabetic microvascular complications, namely, diabetic kidney disease (DKD), diabetic retinopathy (DR), and diabetic neuropathy (DNP).
UNASSIGNED: First, genome-wide association study (GWAS) summary statistics for GM from the MiBioGen consortium and three main diabetic microvascular complications acquired from the FinnGen research project were assessed. Second, a forward MR analysis was conducted to assess the causality of GM on the risk of DKD, DR, and DNP. Third, a series of sensitivity studies, such as heterogeneity tests, pleiotropy evaluations, and leave-one-out analyses, were further conducted to assess the accuracy of MR analysis. Finally, Steiger tests and reverse MR analyses were performed to appraise the possibility of reverse causation.
UNASSIGNED: A total of 2,092 single-nucleotide polymorphisms related to 196 bacterial traits were selected as instrumental variables. This two-sample MR analysis provided strongly reasonable evidence that 28 genetically predicted abundance of specific GM that played non-negligible roles in the occurrence of DKD, DR, and DNP complications were causally associated with 23 GM, the odds ratio of which generally ranged from 0.9 to 1.1. Further sensitivity analysis indicated low heterogeneity, low pleiotropy, and high reliability of the causal estimates.
UNASSIGNED: The study raised the possibility that GM may be a potential target to prevent and delay the progression of diabetic microvascular complications. Further experiments of GM therapy on diabetic microvascular complications are warranted to clarify their effects and specific mechanisms.