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肠道微生物群与 2 型糖尿病之间的因果关系:两样本孟德尔随机研究。

The causal relationship between gut microbiota and type 2 diabetes: a two-sample Mendelian randomized study.

机构信息

School of Medical Laboratory, Weifang Medical College, Weifang, China.

Department of Blood Transfusion, The 960th Hospital of the PLA Jonit Logistics Support Force, Jinan, China.

出版信息

Front Public Health. 2023 Sep 22;11:1255059. doi: 10.3389/fpubh.2023.1255059. eCollection 2023.

DOI:10.3389/fpubh.2023.1255059
PMID:37808975
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10556527/
Abstract

BACKGROUND

Type 2 diabetes mellitus (T2DM) is a commonly observed metabolic anomaly globally, and as of the present time, there's no recognized solution. There is an increasing body of evidence from numerous observational studies indicating a significant correlation between gut flora and metabolic disease progression, particularly in relation to T2DM. Despite this, the direct impact of gut microbiota on T2DM isn't fully understood yet.

METHODS

The summary statistical figures for intestinal microbiota were sourced from the MiBioGen consortium, while the summary statistical data for T2DM were gathered from the Genome-Wide Association Studies (GWAS) database. These datasets were used to execute a two-sample Mendelian randomization (MR) investigation. The Inverse Variance Weighted (IVW), Maximum Likelihood, MR-Egger, Weighted Median, and Weighted Models strategies were employed to assess the impact of gut microbiota on T2DM. Findings were primarily obtained using the IVW technique. Techniques like MR-Egger were employed to identify the occurrence of horizontal pleiotropy among instrumental variables. Meanwhile, Cochran's Q statistical measures were utilized to assess the variability or heterogeneity within these instrumental variables.

RESULTS

The outcomes from the IVW analysis demonstrated that the genus (OR = 0.998, 95% confidence interval: 0.996-1.000, and = 0.038), genus (OR = 0.998, 95% confidence interval: 0.997-0.999, = 0.033), genus (OR = 0.995, 95% confidence interval: 0.993-0.998, = 3.78 × 10), and genus (OR = 0.995, 95% confidence interval: 0.993-0.998, = 8.08 × 10) all acted as defense elements against type 2 diabetes. Family (OR = 1.003, 95% confidence interval: 1.001-1.005, = 0.012), family (OR = 1.0025, 95% confidence interval: 1.000-1.005, = 0.043), genus (OR = 1.003,95% confidence interval: 1.001-1.005, = 4.38 × 10), genus (OR = 1.001,95% confidence interval: 1.000-1.002 = 0.012) were risk factors for type 2 diabetes. False Discovery Rate correction was performed with finding that genus., genus, family and T2DM no longer displayed a significant causal association. In addition, no significant heterogeneity or horizontal pleiotropy was found for instrumental variable.

CONCLUSION

This MR study relies on genetic variation tools to confirm the causal effect of genus , genus , family , genus and genus on T2DM in the gut microbiome, providing new directions and strategies for the treatment and early screening of T2DM, which carries significant clinical relevance. To develop new biomarkers and better understand targeted prevention strategies for T2DM, further comprehensive investigations are required into the protective and detrimental mechanisms exerted by these five genera against T2DM.

摘要

背景

2 型糖尿病(T2DM)是一种全球常见的代谢异常疾病,目前尚无公认的解决方案。越来越多的观察性研究证据表明,肠道菌群与代谢性疾病的发展,特别是与 T2DM 之间存在显著相关性。尽管如此,肠道微生物群对 T2DM 的直接影响尚未完全了解。

方法

肠道微生物群的汇总统计数据来自 MiBioGen 联盟,而 T2DM 的汇总统计数据则来自全基因组关联研究(GWAS)数据库。使用这些数据集执行了两样本 Mendelian 随机化(MR)调查。使用逆方差加权(IVW)、最大似然、MR-Egger、加权中位数和加权模型策略来评估肠道微生物群对 T2DM 的影响。主要使用 IVW 技术获得结果。使用 MR-Egger 等技术来识别工具变量中是否存在水平偏倚。同时,使用 Cochran's Q 统计量来评估这些工具变量中的变异性或异质性。

结果

IVW 分析的结果表明,属 (OR = 0.998,95%置信区间:0.996-1.000, = 0.038)、属 (OR = 0.998,95%置信区间:0.997-0.999, = 0.033)、属 (OR = 0.995,95%置信区间:0.993-0.998, = 3.78×10)和属 (OR = 0.995,95%置信区间:0.993-0.998, = 8.08×10)均作为 2 型糖尿病的防御因素。科 (OR = 1.003,95%置信区间:1.001-1.005, = 0.012)、科 (OR = 1.0025,95%置信区间:1.000-1.005, = 0.043)、属 (OR = 1.003,95%置信区间:1.001-1.005, = 4.38×10)、属 (OR = 1.001,95%置信区间:1.000-1.002, = 0.012)是 2 型糖尿病的风险因素。对假发现率进行了修正,发现属 、属 、科和 T2DM 不再显示出显著的因果关联。此外,工具变量未发现显著的异质性或水平偏倚。

结论

本 MR 研究利用遗传变异工具证实了属 、属 、科、属 和属 在肠道微生物群中对 T2DM 的因果效应,为 T2DM 的治疗和早期筛查提供了新的方向和策略,具有重要的临床意义。为了开发新的生物标志物并更好地了解这五个属对 T2DM 的保护和有害机制,需要进一步对其进行全面研究,以制定针对 T2DM 的靶向预防策略。

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