Table_8_Role of immune cells in mediating the effect of gut microbiota on Hashimoto’s thyroiditis: a 2-sample Mendelian randomization study.XLSX

PurposeHashimoto’s thyroiditis (HT) is one of the most commonly encountered types of autoimmune thyroid disorders (AITDs), influenced by environmental factors, genetics, and the immune system. Previous research has shown a correlation between gut microbiota and HT, as well as the involvement of immune cells in its onset and progression. We aimed to investigate whether immune cells act as intermediaries in the causal relationship between gut microbiota and HT.
MethodsIn this study, we conducted bidirectional two-sample Mendelian randomization (MR) analyses to explore the relationship between gut microbiota and HT using data from genome-wide association studies (GWAS) and the MiBioGen study. Subsequently, MR analyses were performed to investigate the interactions between 731 immune cells and gut microbiota. Additionally, an MR analysis was performed to examine the association between HT and these 731 immune cells, using a GWAS dataset that included 3,757 European subjects. This approach provided insights into the impact of 22 million genetic variants on 731 immune cell signatures.
ResultsThere was a causal relationship between the increase in the number of 15 gut microbiota and HT. We observed that the genus Akkermansia, family Alcaligenaceae, family Desulfovibrionaceae, family Verrucomicrobiaceae, class Verrucomicrobiae, order Verrucomicrobiales, phylum Verrucomicrobia, class Alphaproteobacteria, order Desulfovibrionales, genus Ruminococcus torques group, genus Butyrivibrio, and genus Coprococcus3 were negatively correlated with HT. In addition, the genus Intestinimonas, genus Turicibacter, and genus Anaerostipes were positively correlated with HT. We identified EM CD4 + T cells as a mediator between the gut microbiota and HT.
ConclusionIn conclusion, we presented causal associations between the EM CD4 + T cell-mediated gut microbiota and HT, as inferred from the MR findings derived from extensive aggregated GWAS data. Our research offers guidance and direction for treating and preventing HT.

研究目的：桥本甲状腺炎（Hashimoto’s thyroiditis, HT）是最常见的自身免疫性甲状腺疾病（autoimmune thyroid disorders, AITDs）之一，其发病受环境因素、遗传因素与免疫系统的共同影响。既往研究已证实肠道菌群与HT存在关联，同时免疫细胞也参与了该病的发生与发展进程。本研究旨在探究免疫细胞是否为肠道菌群与HT之间因果关联的中介因子。
研究方法：本研究基于全基因组关联研究（genome-wide association studies, GWAS）及MiBioGen研究的数据，开展双向两样本孟德尔随机化（Mendelian randomization, MR）分析，以探究肠道菌群与HT之间的关联。随后，针对731种免疫细胞与肠道菌群的相互作用开展MR分析。此外，本研究还利用包含3757名欧洲受试者的GWAS数据集，针对HT与上述731种免疫细胞之间的关联开展MR分析。本研究方案可揭示2200万个遗传变异对731种免疫细胞特征的影响。
研究结果：15种肠道菌群丰度升高与HT存在因果关联。本研究观察到，阿克曼菌属（Akkermansia）、产碱杆菌科（Alcaligenaceae）、脱硫弧菌科（Desulfovibrionaceae）、疣微菌科（Verrucomicrobiaceae）、疣微菌纲（Verrucomicrobiae）、疣微菌目（Verrucomicrobiales）、疣微菌门（Verrucomicrobia）、α-变形菌纲（Alphaproteobacteria）、脱硫弧菌目（Desulfovibrionales）、瘤胃球菌托克斯群（Ruminococcus torques group）、丁酸弧菌属（Butyrivibrio）以及Coprococcus3属与HT呈负相关。此外，Intestinimonas属、Turicibacter属以及Anaerostipes属与HT呈正相关。本研究证实，效应记忆CD4+T细胞（EM CD4+ T cells）为肠道菌群与HT之间的中介因子。
研究结论：综上，基于大规模整合GWAS数据得到的MR分析结果，本研究证实了效应记忆CD4+T细胞介导的肠道菌群与HT之间存在因果关联。本研究可为HT的治疗与预防提供理论指导与研究方向。