Causal relationship between gut microbiota and diabetes based on Mendelian randomization.

Q3 Medicine

中南大学学报(医学版) Pub Date : 2025-03-28 DOI:10.11817/j.issn.1672-7347.2025.240555

Manjun Luo, Ziye Li, Mengting Sun, Jiapeng Tang, Tingting Wang, Jiabi Qin

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引用次数: 0

Abstract

Objectives: The gut microbiota plays a crucial role in the pathophysiology of various types of diabetes. However, the causal relationship between them has yet to be systematically elucidated. This study aims to explore the potential causal associations between gut microbiota and diabetes using a two-sample Mendelian randomization (MR) analysis, based on multiple taxonomic levels.

Methods: Eligible instrumental variables were extracted from the selected genome-wide association study (GWAS) data on gut microbiota. These were combined with GWAS datasets on type 1 diabetes (T1D), type 2 diabetes (T2D), and gestational diabetes mellitus (GDM) to conduct forward MR analysis, sensitivity analysis, reverse MR analysis, and validation of significant estimates. Microbial taxa with causal effects on T1D, T2D, and GDM were identified based on a comprehensive assessment of all analytical stages.

Results: A total of 2 179, 2 176, and 2 166 single nucleotide polymorphisms (SNP) were included in the MR analyses for gut microbiota with T1D, T2D, and GDM, respectively. MR results indicated causal associations between: Six microbial taxa (Eggerthella, Lachnospira, Bacillales, Desulfovibrionales, Parasutterella, and Turicibacter) and T1D; 9 microbial taxa (Verrucomicrobia, Deltaproteobacteria, Actinomycetales, Desulfovibrionale, Actinomycetaceae, Desulfovibrionaceae, Actinomyces, Alcaligenaceae, and Lachnospiraceae NC2004 group) and T2D; 10 microbial taxa (Betaproteobacteria, Coprobacter, Ruminococcus2, Tenericutes, Clostridia, Methanobacteria, Mollicutes, Methanobacteriales, Methanobacteriaceae, and Methanobrevibacter) and GDM.

Conclusions: This study identified specific gut microbial taxa that may significantly increase or decrease the risk of developing diabetes. Some findings were fully replicated in independent validation datasets. However, the underlying biological mechanisms of these causal relationships warrant further investigation through mechanistic studies and population-based research.

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基于孟德尔随机化的肠道微生物群与糖尿病的因果关系。

目的：肠道微生物群在各种类型糖尿病的病理生理中起着至关重要的作用。然而，二者之间的因果关系尚未得到系统的阐明。本研究旨在通过基于多个分类水平的双样本孟德尔随机化（MR）分析，探索肠道微生物群与糖尿病之间的潜在因果关系。方法：从选定的肠道微生物群全基因组关联研究（GWAS）数据中提取符合条件的工具变量。将这些数据与1型糖尿病（T1D）、2型糖尿病（T2D）和妊娠糖尿病（GDM）的GWAS数据集相结合，进行正向磁共振分析、敏感性分析、反向磁共振分析和显著性估计的验证。在综合评价各分析阶段的基础上，确定了对T1D、T2D和GDM有因果影响的微生物类群。结果：T1D、T2D和GDM肠道菌群MR分析中分别包含2 179、2 176和2 166个单核苷酸多态性（SNP）。MR结果表明：6个微生物类群（蛋菌、毛螺旋体、芽胞杆菌、Desulfovibrionales、Parasutterella和Turicibacter）与T1D之间存在因果关系；9个微生物类群（Verrucomicrobia、Deltaproteobacteria、放线菌、Desulfovibrionale、放线菌科、Desulfovibrionaceae、放线菌科、Alcaligenaceae和Lachnospiraceae NC2004组）和T2D；10个微生物类群（Betaproteobacteria, Coprobacter, Ruminococcus2, Tenericutes, Clostridia, Methanobacteria, Mollicutes, Methanobacteriales, methanobacteraceae, methanobrebacter）和GDM。结论：本研究确定了可能显著增加或降低患糖尿病风险的特定肠道微生物群。一些发现在独立的验证数据集中被完全重复。然而，这些因果关系的潜在生物学机制需要通过机制研究和基于人群的研究进一步调查。

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来源期刊

中南大学学报(医学版) Medicine-Medicine (all)

CiteScore

1.00

自引率

0.00%

发文量

8237

期刊介绍： Journal of Central South University (Medical Sciences), founded in 1958, is a comprehensive academic journal of medicine and health sponsored by the Ministry of Education and Central South University. The journal has been included in many important databases and authoritative abstract journals at home and abroad, such as the American Medline, Pubmed and its Index Medicus (IM), the Netherlands Medical Abstracts (EM), the American Chemical Abstracts (CA), the WHO Western Pacific Region Medical Index (WPRIM), and the Chinese Science Citation Database (Core Database) (CSCD); it is a statistical source journal of Chinese scientific and technological papers, a Chinese core journal, and a "double-effect" journal of the Chinese Journal Matrix; it is the "2nd, 3rd, and 4th China University Excellent Science and Technology Journal", "2008 China Excellent Science and Technology Journal", "RCCSE China Authoritative Academic Journal (A+)" and Hunan Province's "Top Ten Science and Technology Journals". The purpose of the journal is to reflect the new achievements, new technologies, and new experiences in medical research, medical treatment, and teaching, report new medical trends at home and abroad, promote academic exchanges, improve academic standards, and promote scientific and technological progress.