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ORIGINAL RESEARCH article

Front. Microbiol.
Sec. Microorganisms in Vertebrate Digestive Systems
Volume 15 - 2024 | doi: 10.3389/fmicb.2024.1443643

Gut Microbiota and Autoimmune Thyroid Disease: A Bidirectional Mendelian Randomization Study and Mediation Analysis

Provisionally accepted
Yiqiao Fang Yiqiao Fang Xinyue Zhang Xinyue Zhang Rui Huang Rui Huang Jiaye Liu Jiaye Liu Zhihui Li Zhihui Li *
  • West China Hospital, Sichuan University, Chengdu, China

The final, formatted version of the article will be published soon.

    The gut microbiota (GM) plays a pivotal role in influencing various health outcomes, including immune-mediated conditions, but its potential association with autoimmune thyroid disease (AITD) remains underexplored. We aimed to investigate the potentially pathogenic or protective causal impacts of specific GM on two types of AITD, namely Graves' disease and Hashimoto's thyroiditis, and analyzed the mediating effect of 731 immune cell phenotypes.Methods: Leveraging pooled genome-wide association study (GWAS) data of 211 gut microbiota traits, 731 immune cell phenotypes, and two types of AITD (Hashimoto's thyroiditis and Graves' disease), we performed bidirectional Mendelian randomization (MR) analyses to explore the causal relationships between the GM and AITD. Subsequently, we employed a multivariable MR analysis to discover potential mediating immune cell traits.Additionally, sensitivity analyses were utilized to ensure the reliability of the outcomes.Results: Our analysis revealed that a total of 7 GM taxa were positively associated with AITD, and other 14 taxa showed a negative correlation with AITD. Furthermore, we identified several immune cell traits that mediated the effects of GM on AITD. Most notably, Actinobacteria (p) presented protective effects on Hashimoto's thyroiditis via CCR2 on myeloid Dendritic Cell (5.0%), and Bifidobacterium (g) showed facilitating effects on Graves' disease through CD39+ CD4+ T cell %CD4+ T cell (5.0%) and CD14 on CD33+ HLA DR+ CD14dim (12.2%).The current MR study provides evidence supporting the causal relationships between several specific GM taxa and AITD, and further identified potential mediating immunophenotypes.

    Keywords: Autoimmune thyroid disease, Gut microbiota, Immune cell traits, Mendelian randomization analyses, Mediation analysis Abbreviations： AC: absolute cell counts, AITD: autoimmune thyroid disease, CCL2: chemokine ligand 2, CCR2: chemokine receptor 2, GD: Graves' disease, GM: gut microbiota, GWAS: genomewide association study, HT: Hashimoto's thyroiditis

    Received: 04 Jun 2024; Accepted: 03 Sep 2024.

    Copyright: © 2024 Fang, Zhang, Huang, Liu and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Zhihui Li, West China Hospital, Sichuan University, Chengdu, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.