Table_8_Cross-talk between the gut microbiota and hypothyroidism: a bidirectional two-sample Mendelian randomization study.xlsx

BackgroundMultiple observational studies suggest a connection between the composition of the gut microbiota and hypothyroidism. However, it has yet to be determined whether the gut microbiota has a causal effect on hypothyroidism.MethodsTo investigate the connection between the gut microbiota and hypothyroidism, two-sample Mendelian randomization was performed using data from a genome-wide association study meta-analysis (n = 18,430) conducted by the MiBioGen consortium. Summary statistics for hypothyroidism (26,342 cases and 59,827 controls) were obtained using the data from the FinnGen consortium R8 release data. To investigate the causal link between the gut microbiota and hypothyroidism, various methods, including MR-Egger, weighted median, weighted model, simple model, MR-PRESSO, and inverse variance weighted (IVW), were employed. The bacteria that were causally linked to hypothyroidism in forward Mendelian randomization analysis were subjected to reverse Mendelian randomization analysis. Cochran’s Q statistics were utilized to gauge the heterogeneity of the instrumental variables.ResultsThe results indicated that Akkermansia had a positive impact on hypothyroidism, with an odds ratio of 0.84 (95% CI 0.74–0.95, p = 0.01) based on the inverse variance-weighted estimates. Additionally, Anaerostipes (OR = 1.17, 95% CI 1.01–1.36, p = 0.04), Butyrivibrio (OR = 0.93, 95% CI 0.88–0.99, p = 0.02), Holdemania (OR = 0.89, 95% CI 0.81–0.99, p = 0.03), Intestinimonas (OR = 1.13, 95% CI 1.02–1.26, p = 0.03), Ruminiclostridium5 (OR = 1.19, 95% CI 1.01–1.41, p = 0.04), and Ruminococcaceae UCG-011 (OR = 0.91, 95% CI 0.84–0.99, p = 0.03) were identified. The gut microbiota was not significantly affected by hypothyroidism, as indicated by the results of the reverse MR analysis. There was no significant variation in the instrumental variables or horizontal pleiotropy.ConclusionThe findings of this study using two-sample Mendelian randomization indicate a causal relationship between Akkermansia and hypothyroidism. Increased Akkermansia inhibits the onset and progression of hypothyroidism. Additional randomized controlled experiments are necessary to elucidate the beneficial impact of probiotics on hypothyroidism and their distinct protective mechanisms.

背景：多项观察性研究表明，肠道菌群组成与甲状腺功能减退之间存在关联。然而，肠道菌群是否对甲状腺功能减退具有因果效应尚未确定。方法：为了探究肠道菌群与甲状腺功能减退之间的联系，本研究采用来自 MiBioGen 联盟的基因组关联研究荟萃分析（n=18,430）的数据，执行了双样本孟德尔随机化分析。利用 FinnGen 联盟 R8 版本发布的数据，获得了甲状腺功能减退的汇总统计量（26,342 例病例和 59,827 名对照者）。为了探究肠道菌群与甲状腺功能减退之间的因果关系，采用了多种方法，包括 MR-Egger、加权中位数、加权模型、简单模型、MR-PRESSO 和逆方差加权（IVW）。在正向孟德尔随机化分析中，与甲状腺功能减退因果关联的细菌接受了反向孟德尔随机化分析。通过 Cochran 的 Q 统计量来评估工具变量的异质性。结果：结果表明，Akkermansia 对甲状腺功能减退具有积极影响，基于逆方差加权估计的比值比为 0.84（95% CI 0.74–0.95，p=0.01）。此外，Anaerostipes（OR=1.17，95% CI 1.01–1.36，p=0.04）、Butyrivibrio（OR=0.93，95% CI 0.88–0.99，p=0.02）、Holdemania（OR=0.89，95% CI 0.81–0.99，p=0.03）、Intestinimonas（OR=1.13，95% CI 1.02–1.26，p=0.03）、Ruminiclostridium5（OR=1.19，95% CI 1.01–1.41，p=0.04）和 Ruminococcaceae UCG-011（OR=0.91，95% CI 0.84–0.99，p=0.03）也被识别出来。反向孟德尔随机化分析的结果显示，肠道菌群并未受到甲状腺功能减退的显著影响。工具变量或水平多效性不存在显著差异。结论：本研究利用双样本孟德尔随机化分析的结果表明，Akkermansia 与甲状腺功能减退之间存在因果关系。Akkermansia 的增加抑制了甲状腺功能减退的发生和发展。为进一步阐明益生菌对甲状腺功能减退的益处及其独特的保护机制，需要进行更多的随机对照实验。