Vitamin D and gut microbiota in thyroid diseases: mechanisms and therapeutic potential

Thyroid diseases have become the most common endocrine disorders globally, including hyperthyroidism, hypothyroidism, thyroid nodules (TN), and thyroid cancer (TC). Traditionally, the pathogenesis was attributed to autoimmune dysfunction, iodine metabolism imbalance, and genetic-environmental interactions. Recently, research suggests that vitamin D deficiency and gut microbiota dysbiosis are prevalent in patients with thyroid disorders, particularly in autoimmune thyroid disease (AITD). Vitamin D, as well as gut microbiota and its metabolites, such as short-chain fatty acids and bile acids, jointly regulate innate and adaptive immunity. They also mitigate intestinal leakage by maintaining intestinal barrier integrity, thereby influencing the development and progression of thyroid diseases. Furthermore, studies confirm the bidirectional interaction between vitamin D and the gut microbiota. Vitamin D supplementation increases the abundance of beneficial bacteria and regulates their metabolites. While beneficial bacteria and their metabolites, such as butyrate and bile acids, promote vitamin D receptor (VDR) expression and enhance vitamin D bioavailability. In this review, we integrate existing current basic and clinical evidence to systematically dissect the individual functions and reciprocal crosstalk of vitamin D and gut microbiota in thyroid diseases. Furthermore, we put forward a combined intervention of vitamin D and gut microbiota, which may serve as a viable therapeutic strategy for thyroid disease.