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

Manjun Luo; Mengting Sun; Tingting Wang; Senmao Zhang; Xinli Song; Xiaoying Liu; Jianhui Wei; Qian Chen; Taowei Zhong; Jiabi Qin

doi:10.3389/fcimb.2023.1163898

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

Front Cell Infect Microbiol. 2023 May 29:13:1163898. doi: 10.3389/fcimb.2023.1163898. eCollection 2023.

Authors

Manjun Luo¹, Mengting Sun¹, Tingting Wang¹, Senmao Zhang¹, Xinli Song¹, Xiaoying Liu^{2

3}, Jianhui Wei¹, Qian Chen¹, Taowei Zhong¹, Jiabi Qin^{1

4}

Affiliations

¹ Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha, China.
² Changsha Medical University Public Health Institute, Changsha, China.
³ The Hospital of Trade-Business in Hunan Province, Changsha, China.
⁴ Hunan Provincial Key Laboratory of Clinical Epidemiology, Changsha, China.

Abstract

Objective: The 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.

Methods: We 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.

Results: At 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, P _FDR = 0.085), Bacteroidales order (OR = 1.28, 95% CI = 1.06-1.53, P = 0.009, P _FDR = 0.085), and Eubacterium eligens group genus (OR = 0.64, 95% CI = 0.50-0.81, P = 2.84×10^-4, P _FDR = 0.031) were observed to have a causal relationship with T1D in the IVW analysis. No heterogeneity and pleiotropy were detected.

Conclusions: The 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.

Keywords: Mendelian randomization; T1D; causality; gut microbiota; phylum.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Bacteroidetes / genetics
Diabetes Mellitus, Type 1* / genetics
Gastrointestinal Microbiome* / genetics
Genome-Wide Association Study
Humans
Mendelian Randomization Analysis

Supplementary concepts

Eubacterium eligens

Grants and funding

This research was supported by the Project Funded by the National Key Research and Development Project (2018YFE0114500), National Natural Science Foundation Program of China (82073653 and 81803313), Hunan Outstanding Youth Fund Project (2022JJ10087), Hunan Provincial Science and Technology Talent Support Project (2020TJ-N07), China Postdoctoral Science Foundation (2020M682644), Hunan Provincial Key Research and Development Program (2018SK2063), Open Project from NHC Key Laboratory of Birth Defect for Research and Prevention (KF2020006), Natural Science Foundation of Hunan Province (2018JJ2551 and 2022JJ40207), and Science and Technology Planning Project of Guangdong Province (2020A1414010152).