Gut Microbiota in Hypothyroidism: Pathogenic Mechanisms and Opportunities for Precision Microbiome Interventions

Tao Jiang¹Xiuqing Yang²Baihui Wu²Runchao Tao²Rongbing Chen³Libo Jin¹Da Sun^2*Huibin Weng^4*

• ¹Institute of Life Sciences & Biomedical Collaborative Innovation Center of Zhejiang Province, Wenzhou University, Wenzhou, China
• ²College of Life and Environmental Science, Wenzhou University, Wenzhou, China
• ³Department of Biomedical Engineering, City University of Hong Kong, Hong Kong, Hong Kong, SAR China
• ⁴The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People’s Hospital, Wenzhou Medical University, Wenzhou, China

Hypothyroidism is a common endocrine disorder characterized by insufficient 18 thyroid hormone synthesis or secretion, most frequently caused by Hashimoto's 19 thyroiditis, an autoimmune condition that leads to chronic thyroid gland damage. 20 Despite the widespread use of levothyroxine replacement therapy, a substantial 21 proportion of patients continue to experience persistent symptoms and metabolic 22 dysregulation even after achieving biochemical euthyroidism. These observations 23 have prompted growing interest in non-hormonal contributors to hypothyroidism, 24 particularly the role of the gut microbiota. Recent studies indicate that gut microbial 25 dysbiosis may influence the onset and progression of hypothyroidism through 26 mechanisms involving immune dysregulation, increased intestinal permeability, 27 chronic low-grade inflammation, and impaired nutrient absorption. Additionally, 28 microbial metabolites such as short-chain fatty acids and bile acids are increasingly 29 recognized as modulators of thyroid hormone metabolism, tissue sensitivity, and 30 enterohepatic circulation. The bidirectional interactions between thyroid function and 31 the gut microbiota constitute the emerging concept of the gut–thyroid axis, providing 32 a novel framework for understanding the disease. Microbiota-targeted interventions, 33 including probiotics, prebiotics, synbiotics, and dietary modulation, have 34 demonstrated potential to improve microbial composition, alleviate systemic 35 inflammation, enhance thyroid hormone utilization, and reduce autoantibody levels. 36 This review systematically explores the mechanistic links between gut microbiota and 37 hypothyroidism, critically evaluates current microbiota-based therapeutic strategies, 38 3 and highlights future opportunities for personalized, microbiome-driven interventions 39 to optimize the management of hypothyroidism.