Gut microbiota and type 1 diabetes: a two-sample bidirectional Mendelian randomization study

Frontiers in Cellular and Infection Microbiology

Cellular and Infection Microbiology

Xiaoying Liu¹  Senmao Zhang²  Tingting Wang²  Qian Chen²  Jianhui Wei²  Mengting Sun²  Xinli Song²  Manjun Luo²  Taowei Zhong²  Jiabi Qin³ 

[1] Changsha Medical University Public Health Institute, Changsha, China;The Hospital of Trade-Business in Hunan Province, Changsha, China;Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha, China;Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha, China;Hunan Provincial Key Laboratory of Clinical Epidemiology, Changsha, China;

关键词: gut microbiota;    T1D;    Mendelian randomization;    causality;    phylum;   

DOI  :  10.3389/fcimb.2023.1163898

 received in 2023-02-14, accepted in 2023-05-12,  发布年份 2023

来源: Frontiers

【 摘 要 】

ObjectiveThe real causal relationship between human gut microbiota and T1D remains unclear and difficult to establish. Herein, we adopted a two-sample bidirectional mendelian randomization (MR) study to evaluate the causality between gut microbiota and T1D.MethodsWe leveraged publicly available genome-wide association study (GWAS) summary data to perform MR analysis. The gut microbiota-related GWAS data from 18,340 individuals from the international consortium MiBioGen were used. The summary statistic data for T1D (n = 264,137) were obtained from the latest release from the FinnGen consortium as the outcome of interest. The selection of instrumental variables conformed strictly to a series of preset inclusion and exclusion criteria. MR-Egger, weighted median, inverse variance weighted (IVW), and weighted mode methods were used to assess the causal association. The Cochran’s Q test, MR-Egger intercept test, and leave-one-out analysis were conducted to identify heterogeneity and pleiotropy.ResultsAt the phylum level, only Bacteroidetes was indicated to have causality on T1D (OR = 1.24, 95% CI = 1.01-1.53, P = 0.044) in the IVW analysis. When it comes to their subcategories, Bacteroidia class (OR = 1.28, 95% CI = 1.06-1.53, P = 0.009, PFDR = 0.085), Bacteroidales order (OR = 1.28, 95% CI = 1.06-1.53, P = 0.009, PFDR = 0.085), and Eubacterium eligens group genus (OR = 0.64, 95% CI = 0.50-0.81, P = 2.84×10-4, PFDR = 0.031) were observed to have a causal relationship with T1D in the IVW analysis. No heterogeneity and pleiotropy were detected.ConclusionsThe present study reports that Bacteroidetes phylum, Bacteroidia class, and Bacteroidales order causally increase T1D risk, whereas Eubacterium eligens group genus, which belongs to the Firmicutes phylum, causally decreases T1D risk. Nevertheless, future studies are warranted to dissect the underlying mechanisms of specific bacterial taxa’s role in the pathophysiology of T1D.

【 授权许可】

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Copyright © 2023 Luo, Sun, Wang, Zhang, Song, Liu, Wei, Chen, Zhong and Qin