循环炎症细胞因子作为肠道微生物群与2型糖尿病之间介质的鉴定：一项孟德尔随机化研究

Identification of circulating inflammation cytokines as a mediator of gut microbiota and type 2 diabetes mellitus: a Mendelian randomization study.

作者信息

Zhou Xin, Zheng Wenbin, Kong Wen, Zeng Tianshu

机构信息

Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Jianghan District, Wuhan, Hubei, China.

Hubei Provincial Clinical Research Center for Diabetes and Metabolic Disorders, Huazhong University of Science and Technology, Wuhan, Hubei, China.

出版信息

Diabetol Metab Syndr. 2025 Jul 2;17(1):249. doi: 10.1186/s13098-025-01792-8.

DOI:10.1186/s13098-025-01792-8

PMID:40604874

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12220662/

Abstract

BACKGROUND

Several studies have suggested that the gut microbiota (GM) may be associated with type 2 diabetes mellitus (T2DM). However, the causal relationship between GM and T2DM and whether inflammatory cytokines act as mediators remain unclear.

AIMS

To investigate the association between GM and T2DM and the proportion of this association that is mediated through inflammatory cytokines.

METHODS

We conducted a bidirectional and mediation Mendelian randomization (MR) study utilizing data from the genome-wide association studies (GWAS) of four sources of GM taxa (MiBioGen consortium, = 18,340; Dutch Microbiome Project, = 7,738; German biobanks, = 8,956; FINRISK 2002, = 5,959), a meta-analysis of inflammatory proteins ( = 14,824), and European-ancestry T2DM ( = 1,528,967). The inverse variance weighted method was applied as the primary method. And two-step MR was employed to identify potential mediating inflammatory cytokines.

RESULTS

We found evidence for 28 positive and 20 negative causal effects between multiple sources of GM and T2DM using at least two MR methods. And there were 2 positive and 5 negative causal relationships between cytokines and T2DM using at least two MR methods. The mediation MR analysis found that interferon-gamma (IFN-γ) mediated the causal effects of species Kandleria vitulina on T2DM (proportion mediated = 22.5%, = 0.022).

CONCLUSION

The MR study supports the causal effect between Kandleria vitulina species and T2DM, with a potential mediating role played by inflammatory factor IFN-γ. Such result would serve as evidence for GM-targeted and cytokine-targeted therapy to prevent T2DM.

SUPPLEMENTARY INFORMATION

The online version contains supplementary material available at 10.1186/s13098-025-01792-8.

摘要

背景

多项研究表明，肠道微生物群（GM）可能与2型糖尿病（T2DM）有关。然而，GM与T2DM之间的因果关系以及炎性细胞因子是否作为中介仍不清楚。

目的

研究GM与T2DM之间的关联以及这种关联通过炎性细胞因子介导的比例。

方法

我们利用来自四个GM分类群全基因组关联研究（GWAS）的数据进行了双向和中介孟德尔随机化（MR）研究（MiBioGen联盟，n = 18340；荷兰微生物组计划，n = 7738；德国生物银行，n = 8956；FINRISK 2002，n = 5959），对炎性蛋白进行荟萃分析（n = 14824），以及欧洲血统的T2DM（n = 1528967）。采用逆方差加权法作为主要方法。并采用两步MR法确定潜在的介导炎性细胞因子。

结果

我们使用至少两种MR方法发现了多个GM来源与T2DM之间28个正向和20个负向因果效应的证据。使用至少两种MR方法发现细胞因子与T2DM之间存在2个正向和5个负向因果关系。中介MR分析发现，干扰素-γ（IFN-γ）介导了维氏堪德勒酵母物种对T2DM的因果效应（介导比例=22.5%，P = 0.022）。