Fang Yiqiao, Zhang Xinyue, Huang Rui, Liu Jiaye, Li Zhihui
Division of Thyroid Surgery, Department of General Surgery, Laboratory of Thyroid and Parathyroid Diseases, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, China.
Department of Respiratory and Critical Care Medicine, Frontiers Science Center for Disease-Related Molecular Network, Center of Precision Medicine, Precision Medicine Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, China.
Front Microbiol. 2024 Sep 16;15:1443643. doi: 10.3389/fmicb.2024.1443643. eCollection 2024.
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.
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.
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, presented protective effects on Hashimoto's thyroiditis via CCR2 on myeloid Dendritic Cell (5.0%), and 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.
肠道微生物群（GM）在影响各种健康结果（包括免疫介导的疾病）中起着关键作用，但其与自身免疫性甲状腺疾病（AITD）的潜在关联仍未得到充分研究。我们旨在研究特定GM对两种AITD（即格雷夫斯病和桥本甲状腺炎）的潜在致病或保护因果影响，并分析731种免疫细胞表型的中介作用。
利用211种肠道微生物群特征、731种免疫细胞表型和两种AITD（桥本甲状腺炎和格雷夫斯病）的汇总全基因组关联研究（GWAS）数据，我们进行了双向孟德尔随机化（MR）分析，以探索GM与AITD之间的因果关系。随后，我们采用多变量MR分析来发现潜在的中介免疫细胞特征。此外，还进行了敏感性分析以确保结果的可靠性。
我们的分析表明，共有7种GM分类群与AITD呈正相关，另外14种分类群与AITD呈负相关。此外，我们确定了几种介导GM对AITD影响的免疫细胞特征。最值得注意的是， 通过髓样树突状细胞上的CCR2对桥本甲状腺炎具有保护作用（5.0%）， 通过CD39 + CD4 + T细胞%CD4 + T细胞（5.0%）和CD33 + HLA DR + CD14dim上的CD14对格雷夫斯病具有促进作用（12.2%）。
目前的MR研究提供了证据支持几种特定GM分类群与AITD之间的因果关系，并进一步确定了潜在的中介免疫表型。
