Role of Immune Cells in Mediating the Causal Effect of Gut Microbiota on Type 2 Diabetes.

IF 2.5 4区医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Current molecular medicine Pub Date : 2025-01-01 DOI:10.2174/0115665240322713241114051433

Liu Ruifang, Chai Ruiting, Yang Zhaoyang, Li Candong

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Abstract

Background: Previous studies have suggested that gut microbiota and immune system regulation have potential links with type 2 diabetes (T2D). However, the causal association between gut microbiota and T2D and whether immune cells mediate this interaction is unclear.

Methods: A two-sample, two-step Mendelian randomization (MR) study utilizing an initial inverse-variance weighted (IVW) method was performed to explore the causal impact of gut microbiota on T2D and the intermediary role of immune cells.

Results: The MR analysis assigned 4 gut microbiota and metabolic pathways that increase the risk of T2D (G_Prevotella, g_Anaerotruncus, g_Streptococcus.s_ Streptococcus_parasanguinis, and the pathway of PANTO-PWY) and 4 other gut microbiota and metabolic pathways that have a protective effect against T2D (PWY- 5667, PWY-6892, PWY-7221, and the bacterial g_Paraprevotella.s_Paraprevotella_ clara). Furthermore, 17 immune cell traits have been identified as associated with T2D. The finding from mediation MR analysis revealed that PANTO-PWY increases T2D risk via CD3 on HLA DR+ CD4+, whereas PWY-7221 reduces T2D risk through CD4 on CD4 Treg.

Conclusion: The research reveals a mediated causal link between the gut microbiota and T2D via immune cells.

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免疫细胞在肠道菌群对2型糖尿病因果效应中的介导作用

背景：先前的研究表明，肠道微生物群和免疫系统调节与2型糖尿病（T2D）有潜在的联系。然而，肠道微生物群与T2D之间的因果关系以及免疫细胞是否介导这种相互作用尚不清楚。方法：采用初始反方差加权（IVW）方法进行两样本、两步孟德尔随机化（MR）研究，探讨肠道微生物群对T2D的因果影响以及免疫细胞的中介作用。结果：MR分析确定了4种增加T2D风险的肠道微生物群和代谢途径（G_Prevotella, g_Anaerotruncus, g_Streptococcus）。PWY5667、pwy6892、pwy7221和g_Paraprevotella等4种对T2D具有保护作用的肠道菌群和代谢途径。s_Paraprevotella_克拉拉)。此外，已经确定了17种与T2D相关的免疫细胞特征。调解MR分析的结果显示，PANTO-PWY通过HLA DR+ CD4+上的CD3增加T2D风险，而PWY-7221通过CD4对CD4 Treg上的CD4降低T2D风险。结论：该研究揭示了肠道微生物群与T2D之间通过免疫细胞介导的因果关系。

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来源期刊

Current molecular medicine 医学-医学：研究与实验

CiteScore

5.00

自引率

4.00%

发文量

141

审稿时长

4-8 weeks

期刊介绍： Current Molecular Medicine is an interdisciplinary journal focused on providing the readership with current and comprehensive reviews/ mini-reviews, original research articles, short communications/letters and drug clinical trial studies on fundamental molecular mechanisms of disease pathogenesis, the development of molecular-diagnosis and/or novel approaches to rational treatment. The reviews should be of significant interest to basic researchers and clinical investigators in molecular medicine. Periodically the journal invites guest editors to devote an issue on a basic research area that shows promise to advance our understanding of the molecular mechanism(s) of a disease or has potential for clinical applications.