Aamuktha Porika

Background: Hashimoto’s thyroiditis (HT) is an autoimmune thyroid disease characterized by elevated serum autoimmune antibody levels and lymphocytic infiltration.^1,2 With a global prevalence of 7.5%, HT is the leading cause of hypothyroidism in iodine-replete settings.² The etiology of Hashimoto’s thyroiditis is poorly understood but thought to be a complex interplay of genetic and environmental factors.³ This interplay results in lymphocytic infiltration, thyroid cell damage, and the release of autoantibodies. An imbalance between T helper 1 (Th 1) and T helper 2 (Th2) cells with a predominance of Th1 cells is indicative of HT, resulting in thyroid dysfunction and fibrosis.⁴ In some patients, the insidious onset and subclinical presentation of HT often leads to delayed diagnosis and management. Exploring the gut-immune axis may provide insights into its mechanics.^5,1

Methods: PubMed was searched for connections between “Hashimoto’s thyroiditis,” “gut microbiome,” “short chain fatty acids,” “hydrogen sulfide,” “gut-thyroid axis,” “intestinal permeability,” and “zonulin,” excluding studies older than five years from the review.

Results: Autoimmunity can cause a leaky gut, allowing harmful molecules to enter the bloodstream and damage the thyroid.⁵ Studies in Turkey and Brazil found elevated serum zonulin levels in HT patients, correlating with decreased free triiodothyronine levels.^3,6 Dysbiosis worsens this condition. 16S rRNA sequencing of stool samples indicates reduced butyrate-producing bacteria like Bifidobacterium and Clostridium, and increased “harmful” bacteria such as Phascolarctobacterium.^3,7,8 Butyrate, a short-chain fatty acid (SCFA), enhances the intestinal barrier and promotes the production of regulatory T cells (Tregs) and IgA/IgG.⁹ Sodium butyrate supplementation in mice models with HT improves intestinal barrier function, reduces thyroid inflammation, and decreases Th1 and Th2 cell proportions compared to non-supplemented mice.⁸ Fecal microbiota transplantation in mice from HT patients decreases hydrogen sulfide-producing bacteria like Prevotella.¹⁰ Supplementation with hydrogen sulfide alleviates thyroid inflammation and reduces Th1 and Th2 cell proportions in mice receiving FMT from HT patients.¹⁰ However, more research is needed to understand role of Prevotella in human health and its mechanism in HT.¹⁰

Conclusions: Increased serum zonulin levels signal heightened intestinal permeability, while genomic sequencing reveals reduced butyrate and hydrogen sulfide-producing gut bacteria in HT. Levothyroxine is the standard treatment, but not curative. Polydopamine coatings could offer intestinal repair potential, while probiotics like Lactobacillus and Bifidobacterium may stabilize thyroid function.^11,12 New HT biomarkers include increased plasma zonulin levels and decreased SCFA levels.¹³ In addition, lipopolysaccharide  and deoxycholic acid are sensitive indicators of bacterial translocation.¹³ Further studies on the gut-thyroid axis may unveil HT pathophysiology insights, aiding in curative therapies and quicker subclinical diagnosis.

 Works Cited:

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2. Hu X, Chen Y, Shen Y, Tian R, Sheng Y, Que H. Global prevalence and epidemiological trends of Hashimoto’s thyroiditis in adults: A systematic review and meta-analysis. Front Public Health. 2022;10:1020709. Published 2022 Oct 13. doi:10.3389/fpubh.2022.1020709
3. Cayres LCF, de Salis LVV, Rodrigues GSP, et al. Detection of Alterations in the Gut Microbiota and Intestinal Permeability in Patients With Hashimoto Thyroiditis. Front Immunol. 2021;12:579140. Published 2021 Mar 5. doi:10.3389/fimmu.2021.579140
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5. Garrido-Mesa J, Gálvez J, Garrido-Mesa N. Editorial: The gut-immune axis: a complex training ground impacting inflammatory pathologies. Front Immunol. 2023;14:1274761. Published 2023 Aug 23. doi:10.3389/fimmu.2023.1274761
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7. Liu S, An Y, Cao B, Sun R, Ke J, Zhao D. The Composition of Gut Microbiota in Patients Bearing Hashimoto’s Thyroiditis with Euthyroidism and Hypothyroidism. Int J Endocrinol. 2020;2020:5036959. Published 2020 Nov 10. doi:10.1155/2020/5036959
8. Gong B, Meng F, Wang X, et al. Effects of iodine intake on gut microbiota and gut metabolites in Hashimoto thyroiditis-diseased humans and mice. Commun Biol. 2024;7(1):136. Published 2024 Jan 29. doi:10.1038/s42003-024-05813-6
9. Siddiqui MT, Cresci GAM. The Immunomodulatory Functions of Butyrate. J Inflamm Res. 2021;14:6025-6041. Published 2021 Nov 18. doi:10.2147/JIR.S300989
10. Zhang S, Zhao XQ, Wang X, et al. Gut microecology may be involved in the pathogenesis of hashimoto thyroiditis by reducing production of hydrogen sulfide. The Journal of Clinical Endocrinology & Metabolism. Published online October 4, 2023. doi:10.1210/clinem/dgad588
11. Zhao Y, He R, Zang J, et al. Pathologically catalyzed physical coating restores the intestinal barrier for inflammatory bowel disease therapy. J Nanobiotechnology. 2023;21(1):444. Published 2023 Nov 24. doi:10.1186/s12951-023-02227-0
12. Spaggiari G, Brigante G, De Vincentis S, et al. Probiotics Ingestion Does Not Directly Affect Thyroid Hormonal Parameters in Hypothyroid Patients on Levothyroxine Treatment. Front Endocrinol (Lausanne). 2017;8:316. Published 2017 Nov 14. doi:10.3389/fendo.2017.00316
13. Zhu, X., Zhang, C., Feng, S. et al. Intestinal microbiota regulates the gut-thyroid axis: the new dawn of improving Hashimoto thyroiditis. Clin Exp Med 24, 39 (2024). https://doi.org/10.1007/s10238-024-01304-4