Thyroxine metabolism is an important topic of pathogenesis research and treatment schedule of subclinical hypothyroidism (SCH). L-Thyroxine replacement therapy (LRT) is usually recommended for severe SCH patients only. Our previous studies reported that disordered serum lipid of mild SCH people could also benefit from LRT. However, the benefits were different among individuals, as shown by the variations in drug dosage that required to maintain thyroid-stimulating hormone (TSH) stability. Alternative pathways, such as sulfation and glucuronidation of iodothyronine, may play a role in thyroid hormones metabolism in peripheral tissues aside from thyroid. Conjugated thyroxine can be hydrolyzed and reused in tissues including gastrointestinal tract, in which gut microbiota are one of the most attractive physiological components. On this site, the roles of gut microbiota in thyroidal metabolism should be valued. In this study, a cross-sectional study was performed by analyzing 16S rDNA of gut microbiota in mild SCH patients treated with L-thyroxine or not. Subjects were divided by serum lipid level, L-thyroxine treatment, or L-thyroxine dosage, respectively. Relationship between gut microbiome and serum profile, L-thyroxine treatment, and dose were discussed. Other metabolic disorders such as type 2 diabetes and hypertension were also taken into consideration. It turned out that microbiome varied among individuals divided by dose and the increment of L-thyroxine but not by serum lipid profile. Relative abundance of certain species that were associated with thyroxine metabolism were found varied among different L-thyroxine doses although in relatively low abundance. Moreover, serum cholesterol may perform relevance effects with L-thyroxine in shaping microbiome. Our findings suggested that the differences in L-thyroxine dosage required to maintain TSH level stability, as well as the SCH development, which was displayed by the increased L-thyroxine doses in subsequent follow-up, had relationship with gut microbial composition. The reason may due to the differences in thyroxine metabolic capacity in gut. In addition, the metabolic similarity of iodothyronines and bile acid in gut also provides possibilities for the correlation between host's thyroxine and cholesterol levels.

This study was registered with ClinicalTrials.gov as number NCT01848171.

甲状腺素代谢是亚临床甲状腺功能减退症（SCH）的发病机理研究和治疗计划的重要课题。通常仅建议重度SCH患者使用L-甲状腺素替代疗法（LRT）。我们以前的研究报道，轻度SCH患者的血脂异常也可以从LRT中受益。但是，如需维持甲状腺刺激激素（TSH）稳定性所需的药物剂量不同，则各人的获益是不同的。替代途径，例如碘甲状腺素的硫酸化和葡萄糖醛酸化，可能在除甲状腺外的周围组织的甲状腺激素代谢中起作用。共轭甲状腺素可以被水解并在包括胃肠道在内的组织中重复使用，其中肠道菌群是最有吸引力的生理成分之一。在这个网站上 肠道菌群在甲状腺代谢中的作用应得到重视。在这项研究中，通过分析在接受或不接受L-甲状腺素治疗的轻度SCH患者中肠道菌群的16S rDNA进行了横断面研究。用血清脂质水平，L-甲状腺素治疗或L-甲状腺素剂量分别对受试者进行划分。讨论了肠道微生物组与血清状况，L-甲状腺素治疗和剂量之间的关系。还考虑了其​​他代谢性疾病，例如2型糖尿病和高血压。事实证明，个体之间的微生物组各不相同，除以剂量和L-甲状腺素的增量，而不是血清脂质谱。发现某些与甲状腺素代谢有关的物种的相对丰度在不同的L-甲状腺素剂量之间有所不同，尽管相对丰度较低。此外，血清胆固醇可能与L-甲状腺素在塑造微生物组中具有相关性。我们的研究结果表明，维持TSH水平稳定所需的L-甲状腺素剂量差异以及SCH的发展与肠道微生物组成有关，后者由后续随访中L-甲状腺素剂量的增加而显示。原因可能是由于肠道中甲状腺素代谢能力的差异。另外，肠中碘甲状腺素和胆汁酸的代谢相似性也为宿主甲状腺素和胆固醇水平之间的相关性提供了可能性。在随后的随访中，L-甲状腺素剂量的增加显示出该现象与肠道微生物组成有关。原因可能是由于肠道中甲状腺素代谢能力的差异。另外，碘甲状腺素和胆汁酸在肠道中的代谢相似性也为宿主甲状腺素和胆固醇水平之间的相关性提供了可能性。在随后的随访中，L-甲状腺素剂量的增加显示出该现象与肠道微生物组成有关。原因可能是由于肠道中甲状腺素代谢能力的差异。另外，肠中碘甲状腺素和胆汁酸的代谢相似性也为宿主甲状腺素和胆固醇水平之间的相关性提供了可能性。

该研究已在ClinicalTrials.gov上注册，编号为NCT01848171。