Graduate School, Liaoning University of Traditional Chinese Medicine, Shenyang, China.
School of Tranditional Chinese, Liaoning University of Traditional Chinese Medicine, Shenyang, China.
Front Endocrinol (Lausanne). 2023 Sep 26;14:1240752. doi: 10.3389/fendo.2023.1240752. eCollection 2023.
Numerous observational studies have indicated a link between the composition of gut microbiota and thyroid function. Nevertheless, the precise causal relationship between gut microbiota and thyroid function remains uncertain.
In this two-sample Mendelian randomization study, we utilized summary data from a genome-wide association study of gut microbiota composition in 18,340 participants from 24 cohorts, as well as summary statistics on thyroid hormones and thyroid-stimulating hormone from the ThyroidOmics Consortium and summary statistics on hypothyroidism and hyperthyroidism from the FinnGen R8 release. Five different methods, including inverse variance weighting, MR-Egger, weighted median, weighted mode, and simple mode, were employed to examine the causal relationship between gut microbiota and thyroid function. Reverse Mendelian randomization analysis was conducted for taxa identified as having a causal relationship with thyroid function in the Mendelian randomization analysis. To assess the robustness of the results, sensitivity analyses were conducted employing Cochran's Q test, MR-Egger intercept test, MR-PRESSO global test, and leave-one-out analysis.
Through MR analysis of 211 microbial taxa and 4 phenotypes, we identified a total of 34 gut microbiota taxa that were associated with the outcomes. After using the bonferroni method for multiple testing correction, phylum (id.400) had a protective effect on hypothyroidism (OR=0.883, 95% CI: 0.817-0.955, =0.002), and class (id.3087) had a protective effect on hyperthyroidism (OR=0.549, 95% CI: 0.374-0.805, =0.002). According to the results of reverse MR analysis, no significant causal effect of the four phenotypes was found on gut microbiota. No significant horizontal pleiotropy was detected based on MR-Egger intercept test and MR-PRESSO global test.
Through two-sample MR analysis, we identified specific gut microbiota taxa at the genetic level that are predicted to have a causal relationship with thyroid function, which may serve as useful biomarkers for early disease diagnosis.
大量观察性研究表明肠道微生物群的组成与甲状腺功能之间存在关联。然而，肠道微生物群与甲状腺功能之间的确切因果关系仍不确定。
在这项两样本孟德尔随机化研究中，我们利用了来自 24 个队列的 18340 名参与者的肠道微生物群组成的全基因组关联研究的汇总数据，以及甲状腺代谢组学联盟的甲状腺激素和促甲状腺激素的汇总统计数据，以及芬兰基因研究 8 期释放的甲状腺功能减退症和甲状腺功能亢进症的汇总统计数据。我们采用了五种不同的方法，包括逆方差加权、MR-Egger、加权中位数、加权众数和简单众数，来检验肠道微生物群与甲状腺功能之间的因果关系。对于在孟德尔随机化分析中被确定为与甲状腺功能有因果关系的分类群，我们进行了反向孟德尔随机化分析。为了评估结果的稳健性，我们进行了 Cochran's Q 检验、MR-Egger 截距检验、MR-PRESSO 全局检验和单样本剔除分析的敏感性分析。
通过对 211 种微生物分类群和 4 种表型的 MR 分析，我们总共鉴定出 34 种与结果相关的肠道微生物群分类群。在使用 Bonferroni 方法进行多重检验校正后，门（id.400）对甲状腺功能减退症有保护作用（OR=0.883，95%CI：0.817-0.955，=0.002），而类（id.3087）对甲状腺功能亢进症有保护作用（OR=0.549，95%CI：0.374-0.805，=0.002）。根据反向 MR 分析的结果，没有发现四种表型对肠道微生物群有显著的因果影响。MR-Egger 截距检验和 MR-PRESSO 全局检验均未检测到明显的水平多效性。
通过两样本 MR 分析，我们在遗传水平上确定了特定的肠道微生物群分类群，这些分类群被预测与甲状腺功能有因果关系，它们可能成为早期疾病诊断的有用生物标志物。
