Autoimmun Rev. 2026 Jun 19:104123. doi: 10.1016/j.autrev.2026.104123. Online ahead of print.
ABSTRACT
The gut-thyroid axis has emerged as a pivotal area of research in endocrinology. Growing evidence suggests that gut microbiota (GM) dysbiosis is implicated in the pathogenesis of thyroid diseases. Short-chain fatty acids (SCFAs), key microbial metabolites, are proposed as critical mediators in this interplay, but a comprehensive synthesis of their roles is needed. This review provides an overview of the mechanisms and therapeutic potential of SCFAs in thyroid diseases. Patients with thyroid diseases commonly exhibit gut microbiota dysbiosis, characterized by reduced SCFA-producing bacteria and decreased systemic SCFA levels. Mechanistically, SCFAs regulate immune and metabolic homeostasis through G protein-coupled receptor signaling, histone deacetylase inhibition, mitochondrial metabolism, mTOR-S6K signaling, and intestinal barrier protection. Their deficiency may disrupt immune tolerance, promoting autoimmunity and tumor progression. However, current research remains largely correlative, with insufficient mechanistic evidence. SCFAs are central to gut-thyroid crosstalk. Targeting SCFA pathways through probiotics, prebiotics, or microbiota transplantation represents a promising therapeutic frontier. Future research must prioritize establishing causality using advanced models and validating these approaches in rigorous clinical trials to pave the way for personalized microbiome-based therapies for thyroid diseases.
PMID:42320851 | DOI:10.1016/j.autrev.2026.104123