Microbiome and thyroid diseases: future precision studies of the gut-thyroid axis to facilitate the adjuvant treatment
-
Arman Karimi Behnagh
,
Mahsa Bourbour
,
Sakineh Moghaddam Shiri
,
Omolbanin Asadi
,
Maryam Honardoost
Abstract
Background and Objectives: The gut microbiome is a key determinant of overall health, impacting numerous bodily functions, such as those of the endocrine glands. The effect of the microbiota on thyroid function has become a matter of interest, more so since the revelation of the possible link between intestinal disease and autoimmune thyroid disorders (AITDs). This review aims to provide an in-depth insight into the possible link between gut microbiota and thyroid diseases and metabolism of thyroid hormones.
Materials and Methods: A set of online sources including, PubMed, Scopus, Google Scholar and CENTRAL were comprehensively searched to find the studies relevant to the topic of the review. Only reports in English were included in this review.
Results: It has been proposed that damage to the intestinal barrier is a key element in the passage of antigens from the lumen into the bloodstream and their subsequent contact with the immune system. In addition to AITDs, dysbiosis has been shown to be linked with thyroid cancers, in which higher counts of certain bacteria associated with inflammation and carcinogenesis have been identified.
Conclusion: The majority of the available literature is focused on the differences in the microbial strain composition in individuals with thyroid disorders compared to that of healthy controls. Nonetheless, the current body of evidence has implied on possible role gut microbiome in the development of thyroid diseases.
1. Koenig JE, Spor A, Scalfone N, Fricker AD, Stombaugh J, Knight R, et al. Succession of microbial consortia in the developing infant gut microbiome. Proc Natl Acad Sci U S A 2011;108 Suppl 1:4578-4585.
2. Wampach L, Heintz-Buschart A, Fritz JV, Ramiro-Garcia J, Habier J, Herold M, et al. Birth mode is associated with earliest strain-conferred gut microbiome functions and immunostimulatory potential. Nat Commun 2018;9:5091.
3. Derrien M, Alvarez AS, de Vos WM. The Gut Microbiota in the First Decade of Life. Trends Microbiol 2019;27:997-1010.
4. Jandhyala SM, Talukdar R, Subramanyam C, Vuyyuru H, Sasikala M, Reddy DN. Role of the normal gut microbiota. World J Surg 2015;21:8787.
5. Nicholson JK, Holmes E, Kinross J, Burcelin R, Gibson G, Jia W, et al. Host-gut microbiota metabolic interactions. Science 2012;336:1262-1267.
6. Degnan PH, Taga ME, Goodman AL. Vitamin B12 as a modulator of gut microbial ecology. Cell Metab 2014;20:769-78.
7. Wiertsema SP, van Bergenhenegouwen J, Garssen J, Knippels LMJ. The Interplay between the Gut Microbiome and the Immune System in the Context of Infectious Diseases throughout Life and the Role of Nutrition in Optimizing Treatment Strategies. Nutrients 2021;13:886.
8. Carding S, Verbeke K, Vipond DT, Corfe BM, Owen LJ. Dysbiosis of the gut microbiota in disease. Microb Ecol Health Dis 2015;26:26191.
9. Han H, Li Y, Fang J, Liu G, Yin J, Li T, et al. Gut microbiota and type 1 diabetes. Int J Mole Sci 2018;19:995.
10. Jamshidi P, Hasanzadeh S, Tahvildari A, Farsi Y, Arbabi M, Mota JF, et al. Is there any association between gut microbiota and type 1 diabetes? A systematic review. Gut pathogens 2019;11:1-10.
11. Clemente JC, Ursell LK, Parfrey LW, Knight R. The impact of the gut microbiota on human health: an integrative view. Cell 2012;148:1258-1270.
12. Tamboli CP, Neut C, Desreumaux P, Colombel JF. Dysbiosis in inflammatory bowel disease. Gut 2004;53:1-4.
13. Knezevic J, Starchl C, Tmava Berisha A, Amrein K. Thyroid-gut-axis: how does the microbiota influence thyroid function? Nutrients 2020;12:1769.
14. Virili C, Centanni M. Does microbiota composition affect thyroid homeostasis? Endocrine 2015;49:583-587.
15. Shen CT, Zhang Y, Liu YM, Yin S, Zhang XY, Wei WJ, et al. A distinct serum metabolic signature of distant metastatic papillary thyroid carcinoma. Clin Endocrinol (Oxf) 2017;87:844-852.
16. Lim H, Devesa SS, Sosa JA, Check D, Kitahara CM. Trends in thyroid cancer incidence and mortality in the United States, 1974-2013. JAMA 2017;317:1338-1348.
17. Li A, Li T, Gao X, Yan H, Chen J, Huang M, et al. Gut Microbiome Alterations in Patients With Thyroid Nodules. Front Cell Infect Microbiol 2021;11:643968.
18. Fang L, Ning J. Recent advances in gut microbiota and thyroid disease: pathogenesis and therapeutics in autoimmune, neoplastic, and nodular conditions. Front Cell Infect Microbiol 2024;14:1465928.
19. Fröhlich E, Wahl R. Microbiota and thyroid interaction in health and disease. Trends Endocrinol Metab 2019;30:479-490.
20. Michalaki M, Volonakis S, Mamali I, Kalfarentzos F, Vagenakis AG, Markou KB. Dietary iodine absorption is not influenced by malabsorptive bariatric surgery. Obes Surg 2014;24:1921-1925.
21. Navarro AM, Suen VM, Souza IM, De Oliveira JE, Marchini JS. Patients with severe bowel malabsorption do not have changes in iodine status. Nutrition 2005;21:895-900.
22. Wang R, Yu X, Cai H, Lu G, Gao D, Zhang M, et al. Gut microbiota alteration was related to subclinical hypothyroidism and dyslipidemia in mice. FASEB J 2025;39(5):e70445.
23. Gong B, Meng F, Wang X, Han Y, Yang W, Wang C, et al. Effects of iodine intake on gut microbiota and gut metabolites in Hashimoto thyroiditis-diseased humans and mice. Commun Biol 2024;7:136.
24. Huang Z, Rose AH, Hoffmann PR. The role of selenium in inflammation and immunity: from molecular mechanisms to therapeutic opportunities. Antioxid Redox Signal 2012;16:705-743.
25. Przybylik-Mazurek E, Zagrodzki P, Kuzniarz-Rymarz S, Hubalewska-Dydejczyk A. Thyroid disorders-assessments of trace elements, clinical, and laboratory parameters. Biol Trace Elem Res 2011;141:65-75.
26. Rostami R, Nourooz-Zadeh S, Mohammadi A, Khalkhali HR, Ferns G, Nourooz-Zadeh J. Serum Selenium Status and Its Interrelationship with Serum Biomarkers of Thyroid Function and Antioxidant Defense in Hashimoto's Thyroiditis. Antioxidants (Basel) 2020;9:1070.
27. Wimmer I, Hartmann T, Brustbauer R, Minear G, Dam K. Selenium levels in patients with autoimmune thyroiditis and controls in lower Austria. Horm Metab Res 2014;46:707-709.
28. Ren G, Yu M, Li K, Hu Y, Wang Y, Xu X, et al. Seleno-lentinan prevents chronic pancreatitis development and modulates gut microbiota in mice. J Func Foods 2016;22:177-188.
29. Ertek S, Cicero AF, Caglar O, Erdogan G. Relationship between serum zinc levels, thyroid hormones and thyroid volume following successful iodine supplementation. Hormones (Athens) 2010;9:263-268.
30. Kandhro GA, Kazi TG, Afridi HI, Kazi N, Baig JA, Arain MB, et al. Effect of zinc supplementation on the zinc level in serum and urine and their relation to thyroid hormone profile in male and female goitrous patients. Clin Nutr 2009;28:162-168.
31. Larsen PR, Zavacki AM. The role of the iodothyronine deiodinases in the physiology and pathophysiology of thyroid hormone action. Eur Thyroid J 2012;1:232-242.
32. Arora M, Mahat RK, Kumar S, Mustafa I, Sah SP. Study of trace elements in patients of hypothyroidism with special reference to zinc and copper. Biomed J 2018;2:5.
33. Kazi TG, Kandhro GA, Sirajuddin, Afridi HI, Baig JA, Shah AQ, et al. Evaluation of iodine, iron, and selenium in biological samples of thyroid mother and their newly born babies. Early Hum Dev 2010;86:649-655.
34. Ludgate ME, Masetti G, Soares M. The relationship between the gut microbiota and thyroid disorders. Nat Rev Endocrinol 2024;20:511-525.
35. Virili C, Centanni M. Does microbiota composition affect thyroid homeostasis? Endocrine 2015;49:583-287.
36. Jiang T, Yang X, Wu B, Tao R, Chen R, Jin L, et al. Gut microbiota in hypothyroidism: pathogenic mechanisms and opportunities for precision microbiome interventions. Front. Microbiol 2025;16:1661211.
37. Yao Z, Zhao M, Gong Y, Chen W, Wang Q, Fu Y, et al. Relation of Gut Microbes and L-Thyroxine Through Altered Thyroxine Metabolism in Subclinical Hypothyroidism Subjects. Front Cell Infect Microbiol 2020;10:495.
38. Köhling HL, Plummer SF, Marchesi JR, Davidge KS, Ludgate M. The microbiota and autoimmunity: Their role in thyroid autoimmune diseases. Clin Immunol 2017;183:63-74.
39. Thiyagarajan S, Saini AM, Alruwaili J. Helicobacter pylori-induced autoimmune thyroiditis: is the pathogenic link concluded or still a hypothesis? Rev Med Microbiol 2018;29:64-72.
40. Simmonds MJ, Gough SC. Unravelling the genetic complexity of autoimmune thyroid disease: HLA, CTLA-4 and beyond. Clin Exp Immunol 2004;136:1-10.
41. Su X, Zhao Y, Li Y, Ma S, Wang Z. Gut dysbiosis is associated with primary hypothyroidism with interaction on gut-thyroid axis. Clin Sci (Lond) 2020;134:1521-1535.
42. El-Zawawy HT, Ahmed SM, El-Attar EA, Ahmed AA, Roshdy YS, Header DA. Study of gut microbiome in Egyptian patients with autoimmune thyroid diseases. Int J Clin Pract 2021;75(5):e14038.
43. Bassi V, Marino G, Iengo A, Fattoruso O, Santinelli C. Autoimmune thyroid diseases and Helicobacter pylori: the correlation is present only in Graves's disease. World J Surg 2012;18:1093.
44. Völzke H, Werner A, Guertler L, Robinson D, Wallaschofski H, John U. Putative association between anti-Borrelia IgG and autoimmune thyroid disease? Thyroid 2005;15:1273-1277.
45. Kiseleva E, Mikhailopulo K, Sviridov O, Novik G, Knirel Y, Szwajcer Dey E. The role of components of Bifidobacterium and Lactobacillus in pathogenesis and serologic diagnosis of autoimmune thyroid diseases. Benef Microbes 2011;2:139-154.
46. Yang M, Sun B, Li J, Yang B, Xu J, Zhou X, et al. Alteration of the intestinal flora may participate in the development of Graves' disease: a study conducted among the Han population in southwest China. Endocr Connect 2019;8:822-828.
47. Yan HX, An WC, Chen F, An B, Pan Y, Jin J, et al.
Intestinal microbiota changes in Graves' disease: a prospective clinical study. Biosci Rep 2020;40(9):BSR20191242.
48. Ishaq HM, Mohammad IS, Shahzad M, Ma C, Raza MA, Wu X, et al. Molecular Alteration Analysis of Human Gut Microbial Composition in Graves' disease Patients. Int J Biol Sci 2018;14:1558-1570.
49. Cornejo-Pareja I, Ruiz-Limón P, Gómez-Pérez AM, Molina-Vega M, Moreno-Indias I, Tinahones FJ. Differential Microbial Pattern Description in Subjects with Autoimmune-Based Thyroid Diseases: A Pilot Study. J Pers Med 2020;10:192.
50. Omidan N, Zahir ST, Fateh A. Cytological and Pathological Evaluation of Hashimoto's Thyroiditis. Maedica (Bucur) 2019;14:98-103.
51. Ragusa F, Fallahi P, Elia G, Gonnella D, Paparo SR, Giusti C, et al. Hashimotos' thyroiditis: Epidemiology, pathogenesis, clinic and therapy. Best Pract Res Clin Endocrinol Metab 2019;33:101367.
52. Mincer DL, Jialal I. Hashimoto Thyroiditis. StatPearls. Treasure Island (FL)2022.
53. Antonelli A, Ferrari SM, Corrado A, Di Domenicantonio A, Fallahi P. Autoimmune thyroid disorders. Autoimmun Rev 2015;14:174-180.
54. Ferri C, Sebastiani M, Giuggioli D, Colaci M, Fallahi P, Piluso A, et al. Hepatitis C virus syndrome: A constellation of organ- and non-organ specific autoimmune disorders, B-cell non-Hodgkin's lymphoma, and cancer. World J Hepatol 2015;7:327-343.
55. Tomer Y, Davies TF. Searching for the autoimmune thyroid disease susceptibility genes: from gene mapping to gene function. Endocr Rev 2003;24:694-717.
56. Tomer Y, Menconi F. Interferon induced thyroiditis. Best Pract Res Clin Endocrinol Metab 2009;23:703-712.
57. Su X, Zhao Y, Li Y, Ma S, Wang Z. Gut dysbiosis is associated with primary hypothyroidism with interaction on gut-thyroid axis. Clin Sci 2020;134:1521-1535.
58. Zhao H, Yuan L, Zhu D, Sun B, Du J, Wang J. Alterations and mechanism of gut microbiota in graves’ disease and hashimoto’s thyroiditis. Pol J Microbiol 2022;71:173.
59. Zhao F, Feng J, Li J, Zhao L, Liu Y, Chen H, et al. Alterations of the gut microbiota in Hashimoto's thyroiditis patients. Thyroid 2018;28:175-186.
60. 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.
61. Aghili R, Jafarzadeh F, Ghorbani R, Khamseh ME, Salami MA, Malek M. The association of Helicobacter pylori infection with Hashimoto's thyroiditis. Acta Medica Iranica 2013;51:293-296.
62. Bassi V, Santinelli C, Iengo A, Romano C. Identification of a correlation between Helicobacter pylori infection and Graves’ disease. Helicobacter 2010;15:558-562.
63. Franceschi F, Satta MA, Mentella MC, Penland R, Candelli M, Grillo RL, et al. Helicobacter pylori infection in patients with Hashimoto's thyroiditis. Helicobacter 2004;9:369.
64. Shmuely H, Shimon I, Gitter LA. Helicobacter pylori infection in women with Hashimoto thyroiditis: A case-control study. Medicine (Baltimore) 2016;95(29):e4074.
65. Gallo D, Piantanida E, Gallazzi M, Bartalena L, Tanda ML, Bruno A, et al. Immunological Drivers in Graves' Disease: NK Cells as a Master Switcher. Front Endocrinol (Lausanne) 2020;11:406.
66. Li H, Li J. Thyroid disorders in women. Minerva Med 2015;106:109-114.
67. Bartalena L, Tanda ML. Graves' ophthalmopathy. N Engl J Med 2009;360:994-1001.
68. Antonelli A, Ferrari SM, Ragusa F, Elia G, Paparo SR, Ruffilli I, et al. Graves' disease: Epidemiology, genetic and environmental risk factors and viruses. Best Pract Res Clin Endocrinol Metab 2020;34:101387.
69. Masetti G, Moshkelgosha S, Köhling H-L, Covelli D, Banga JP, Berchner-Pfannschmidt U, et al. Gut microbiota in experimental murine model of Graves’ orbitopathy established in different environments may modulate clinical presentation of disease. Microbiome 2018;6:1-15.
70. Zheng D, Liao H, Chen S, Liu X, Mao C, Zhang C, et al. Elevated Levels of Circulating Biomarkers Related to Leaky Gut Syndrome and Bacterial Translocation Are Associated With Graves' Disease. Front Endocrinol (Lausanne) 2021;12:796212.
71. Su X, Yin X, Liu Y, Yan X, Zhang S, Wang X, et al. Gut dysbiosis contributes to the imbalance of Treg and Th17 cells in Graves’ disease patients by propionic acid. J Clin Endocrinol Metab 2020;105:3526-3547.
72. Yang M, Li F, Zhang R, Wu Y, Yang Q, Wang F, et al. Alteration of the Intestinal Microbial Flora and the Serum IL-17 Level in Patients with Graves' Disease Complicated with Vitamin D Deficiency. Int Arch Allergy Immunol 2022;183:225-2234.
73. Jiang W, Yu X, Kosik RO, Song Y, Qiao T, Tong J, et al. Gut Microbiota May Play a Significant Role in the Pathogenesis of Graves' Disease. Thyroid 2021;31:810-820.
74. Shi TT, Xin Z, Hua L, Wang H, Zhao RX, Yang YL, et al. Comparative assessment of gut microbial composition and function in patients with Graves' disease and Graves' orbitopathy. J Endocrinol Invest 2021;44:297-310.
75. Jenq RR, Taur Y, Devlin SM, Ponce DM, Goldberg JD, Ahr KF, et al. Intestinal Blautia Is Associated with Reduced Death from Graft-versus-Host Disease. Biol Blood Marrow Transplant 2015;21:1373-1383.
76. Shi TT, Xin Z, Hua L, Zhao RX, Yang YL, Wang H, et al. Alterations in the intestinal microbiota of patients with severe and active Graves' orbitopathy: a cross-sectional study. J Endocrinol Invest 2019;42:967-978.
77. Chen J, Wang W, Guo Z, Huang S, Lei H, Zang P, et al. Associations between gut microbiota and thyroidal function status in Chinese patients with Graves’ disease. J Endocrinol Invest 2021;44:1913-1926.
78. Aschebrook‐Kilfoy B, Shu XO, Gao YT, Ji BT, Yang G, Li HL, et al. Thyroid cancer risk and dietary nitrate and nitrite intake in the Shanghai women's health study. Int J Cancer 2013;132:897-904.
79. Samimi H, Haghpanah V. Gut Microbiome and Radioiodine-Refractory Papillary Thyroid Carcinoma Pathophysiology. Trends Endocrinol Metab 2020;31:627-630.
80. Zhang J, Zhang F, Zhao C, Xu Q, Liang C, Yang Y, et al. Dysbiosis of the gut microbiome is associated with thyroid cancer and thyroid nodules and correlated with clinical index of thyroid function. Endocrine 2019;64:564-574.
81. Feng J, Zhao F, Sun J, Lin B, Zhao L, Liu Y, et al. Alterations in the gut microbiota and metabolite profiles of thyroid carcinoma patients. Int J cancer 2019;144:2728-2745.
82. Park SJ, Kim M, Jeong S, et al. Association Between Antibiotic Exposure and Thyroid Cancer: A Nationwide Cohort Study in South Korea. Thyroid 2024;34:112-122.
83. Yu X, Jiang W, Kosik RO, Song Y, Luo Q, Qiao T, et al. Gut microbiota changes and its potential relations with thyroid carcinoma. J Adv Res 2022;35:61-70.
84. Dai D, Yang Y, Yang Y, Dang T, Xiao J, Wang W, et al. Alterations of thyroid microbiota across different thyroid microhabitats in patients with thyroid carcinoma. J Transl Med 2021;19:488.
85. Ishaq HM, Mohammad IS, Hussain R, Parveen R, Shirazi JH, Fan Y, et al. Gut-Thyroid axis: How gut microbial dysbiosis associated with euthyroid thyroid cancer. J Cancer 2022;13:2014.
86. Jiang W, Lu G, Gao D, Lv Z, Li D. The relationships between the gut microbiota and its metabolites with thyroid diseases. Front Endocrinol 2022;13:943408.
87. Lu G, Yu X, Jiang W, Luo Q, Tong J, Fan S, et al. Alterations of Gut Microbiome and Metabolite Profiles Associated With Anabatic Lipid Dysmetabolism in Thyroid Cancer. Front Endocrinol 2022;13: 893164.
88. Wang M, Zhu Y. Gut microbiome versus thyroid cancer: Association and clinical implications (Review). Oncol Lett 2025;30:368.
89. Liu CJ, Chen SQ, Zhang SY, Wang JL, Tang XD, Yang KX, et al. The comparison of microbial communities in thyroid tissues from thyroid carcinoma patients. J Microbiol 2021;59:988-1001.
90. Quan Z, Zhang X, Wang S, Meng Y. Causal analysis of the gut microbiota in differentiated thyroid carcinoma: a two-sample Mendelian randomization study. Front Genet 2023;14:1299930.
91. Zheng L, Zhang L, Tang L, Huang D, Pan D, Guo W, et al. Gut microbiota is associated with response to 131I therapy in patients with papillary thyroid carcinoma. Eur J Nucl Med Mol Imaging 2023;50:1453-1465.
92. Aghajani MJ, Cooper A, McGuire H, Jeffries T, Saab J, Ismail K, et al. Pembrolizumab for anaplastic thyroid cancer: a case study. Cancer Immunol Immunother 2019;68:1921-34.
93. Karimi M, Rabiei R, Kazemi K, Motlagh RB, Asbaghi O. Effects of probiotics and synbiotics oral supplementation on thyroid function in adults: a grade-assessed systematic review and meta-analysis. Thyroid Res 2025;18:39.
94. Baurhoo B, Phillip L, Ruiz-Feria C. Effects of purified lignin and mannan oligosaccharides on intestinal integrity and microbial populations in the ceca and litter of broiler chickens. Poul Sci 2007;86:1070-1078.
95. Voicu SN, Scărlătescu AIA, Apetroaei MM, Nedea MII, Blejan IE, Udeanu DI, et al. Evaluation of Neuro-Hormonal Dynamics after the Administration of Probiotic Microbial Strains in a Murine Model of Hyperthyroidism. Nutrients 2024;16:1077.
96. Zhu X, Zhang C, Feng S, He R, Zhang S. Intestinal microbiota regulates the gut-thyroid axis: the new dawn of improving Hashimoto thyroiditis. Clin Exp Med 2024;24:39.
97. Osowiecka K, Skrypnik D, Myszkowska-Ryciak J. Assessment of the Impact of Nutritional Intervention with the Probiotic Lactiplantibacillus plantarum 299v on Nutritional Status and Quality of Life of Hashimoto's Thyroiditis Patients-A Randomized Double-Blind Study Protocol. J Pers Med 2023;13:1659.
98. Ramezani M, Reisian M, Sajadi Hezaveh Z. The effect of synbiotic supplementation on hypothyroidism: A randomized double-blind placebo controlled clinical trial. PLoS One 2023;18(2):e0277213.
99. Shu Q, Kang C, Li J, Hou Z, Xiong M, Wang X, et al. Effect of probiotics or prebiotics on thyroid function: A meta-analysis of eight randomized controlled trials. PLoS One 2024;19(1):e0296733.
100. Cheng H, Liu J, Tan Y, Feng W, Peng C. Interactions between gut microbiota and berberine, a necessary procedure to understand the mechanisms of berberine. J Pharm Anal 2022;12:541-55.
101. Yang F, Gao R, Luo X, Liu R, Xiong D. Berberine influences multiple diseases by modifying gut microbiota. Front Nutr 2023;10:1187718.
2. Wampach L, Heintz-Buschart A, Fritz JV, Ramiro-Garcia J, Habier J, Herold M, et al. Birth mode is associated with earliest strain-conferred gut microbiome functions and immunostimulatory potential. Nat Commun 2018;9:5091.
3. Derrien M, Alvarez AS, de Vos WM. The Gut Microbiota in the First Decade of Life. Trends Microbiol 2019;27:997-1010.
4. Jandhyala SM, Talukdar R, Subramanyam C, Vuyyuru H, Sasikala M, Reddy DN. Role of the normal gut microbiota. World J Surg 2015;21:8787.
5. Nicholson JK, Holmes E, Kinross J, Burcelin R, Gibson G, Jia W, et al. Host-gut microbiota metabolic interactions. Science 2012;336:1262-1267.
6. Degnan PH, Taga ME, Goodman AL. Vitamin B12 as a modulator of gut microbial ecology. Cell Metab 2014;20:769-78.
7. Wiertsema SP, van Bergenhenegouwen J, Garssen J, Knippels LMJ. The Interplay between the Gut Microbiome and the Immune System in the Context of Infectious Diseases throughout Life and the Role of Nutrition in Optimizing Treatment Strategies. Nutrients 2021;13:886.
8. Carding S, Verbeke K, Vipond DT, Corfe BM, Owen LJ. Dysbiosis of the gut microbiota in disease. Microb Ecol Health Dis 2015;26:26191.
9. Han H, Li Y, Fang J, Liu G, Yin J, Li T, et al. Gut microbiota and type 1 diabetes. Int J Mole Sci 2018;19:995.
10. Jamshidi P, Hasanzadeh S, Tahvildari A, Farsi Y, Arbabi M, Mota JF, et al. Is there any association between gut microbiota and type 1 diabetes? A systematic review. Gut pathogens 2019;11:1-10.
11. Clemente JC, Ursell LK, Parfrey LW, Knight R. The impact of the gut microbiota on human health: an integrative view. Cell 2012;148:1258-1270.
12. Tamboli CP, Neut C, Desreumaux P, Colombel JF. Dysbiosis in inflammatory bowel disease. Gut 2004;53:1-4.
13. Knezevic J, Starchl C, Tmava Berisha A, Amrein K. Thyroid-gut-axis: how does the microbiota influence thyroid function? Nutrients 2020;12:1769.
14. Virili C, Centanni M. Does microbiota composition affect thyroid homeostasis? Endocrine 2015;49:583-587.
15. Shen CT, Zhang Y, Liu YM, Yin S, Zhang XY, Wei WJ, et al. A distinct serum metabolic signature of distant metastatic papillary thyroid carcinoma. Clin Endocrinol (Oxf) 2017;87:844-852.
16. Lim H, Devesa SS, Sosa JA, Check D, Kitahara CM. Trends in thyroid cancer incidence and mortality in the United States, 1974-2013. JAMA 2017;317:1338-1348.
17. Li A, Li T, Gao X, Yan H, Chen J, Huang M, et al. Gut Microbiome Alterations in Patients With Thyroid Nodules. Front Cell Infect Microbiol 2021;11:643968.
18. Fang L, Ning J. Recent advances in gut microbiota and thyroid disease: pathogenesis and therapeutics in autoimmune, neoplastic, and nodular conditions. Front Cell Infect Microbiol 2024;14:1465928.
19. Fröhlich E, Wahl R. Microbiota and thyroid interaction in health and disease. Trends Endocrinol Metab 2019;30:479-490.
20. Michalaki M, Volonakis S, Mamali I, Kalfarentzos F, Vagenakis AG, Markou KB. Dietary iodine absorption is not influenced by malabsorptive bariatric surgery. Obes Surg 2014;24:1921-1925.
21. Navarro AM, Suen VM, Souza IM, De Oliveira JE, Marchini JS. Patients with severe bowel malabsorption do not have changes in iodine status. Nutrition 2005;21:895-900.
22. Wang R, Yu X, Cai H, Lu G, Gao D, Zhang M, et al. Gut microbiota alteration was related to subclinical hypothyroidism and dyslipidemia in mice. FASEB J 2025;39(5):e70445.
23. Gong B, Meng F, Wang X, Han Y, Yang W, Wang C, et al. Effects of iodine intake on gut microbiota and gut metabolites in Hashimoto thyroiditis-diseased humans and mice. Commun Biol 2024;7:136.
24. Huang Z, Rose AH, Hoffmann PR. The role of selenium in inflammation and immunity: from molecular mechanisms to therapeutic opportunities. Antioxid Redox Signal 2012;16:705-743.
25. Przybylik-Mazurek E, Zagrodzki P, Kuzniarz-Rymarz S, Hubalewska-Dydejczyk A. Thyroid disorders-assessments of trace elements, clinical, and laboratory parameters. Biol Trace Elem Res 2011;141:65-75.
26. Rostami R, Nourooz-Zadeh S, Mohammadi A, Khalkhali HR, Ferns G, Nourooz-Zadeh J. Serum Selenium Status and Its Interrelationship with Serum Biomarkers of Thyroid Function and Antioxidant Defense in Hashimoto's Thyroiditis. Antioxidants (Basel) 2020;9:1070.
27. Wimmer I, Hartmann T, Brustbauer R, Minear G, Dam K. Selenium levels in patients with autoimmune thyroiditis and controls in lower Austria. Horm Metab Res 2014;46:707-709.
28. Ren G, Yu M, Li K, Hu Y, Wang Y, Xu X, et al. Seleno-lentinan prevents chronic pancreatitis development and modulates gut microbiota in mice. J Func Foods 2016;22:177-188.
29. Ertek S, Cicero AF, Caglar O, Erdogan G. Relationship between serum zinc levels, thyroid hormones and thyroid volume following successful iodine supplementation. Hormones (Athens) 2010;9:263-268.
30. Kandhro GA, Kazi TG, Afridi HI, Kazi N, Baig JA, Arain MB, et al. Effect of zinc supplementation on the zinc level in serum and urine and their relation to thyroid hormone profile in male and female goitrous patients. Clin Nutr 2009;28:162-168.
31. Larsen PR, Zavacki AM. The role of the iodothyronine deiodinases in the physiology and pathophysiology of thyroid hormone action. Eur Thyroid J 2012;1:232-242.
32. Arora M, Mahat RK, Kumar S, Mustafa I, Sah SP. Study of trace elements in patients of hypothyroidism with special reference to zinc and copper. Biomed J 2018;2:5.
33. Kazi TG, Kandhro GA, Sirajuddin, Afridi HI, Baig JA, Shah AQ, et al. Evaluation of iodine, iron, and selenium in biological samples of thyroid mother and their newly born babies. Early Hum Dev 2010;86:649-655.
34. Ludgate ME, Masetti G, Soares M. The relationship between the gut microbiota and thyroid disorders. Nat Rev Endocrinol 2024;20:511-525.
35. Virili C, Centanni M. Does microbiota composition affect thyroid homeostasis? Endocrine 2015;49:583-287.
36. Jiang T, Yang X, Wu B, Tao R, Chen R, Jin L, et al. Gut microbiota in hypothyroidism: pathogenic mechanisms and opportunities for precision microbiome interventions. Front. Microbiol 2025;16:1661211.
37. Yao Z, Zhao M, Gong Y, Chen W, Wang Q, Fu Y, et al. Relation of Gut Microbes and L-Thyroxine Through Altered Thyroxine Metabolism in Subclinical Hypothyroidism Subjects. Front Cell Infect Microbiol 2020;10:495.
38. Köhling HL, Plummer SF, Marchesi JR, Davidge KS, Ludgate M. The microbiota and autoimmunity: Their role in thyroid autoimmune diseases. Clin Immunol 2017;183:63-74.
39. Thiyagarajan S, Saini AM, Alruwaili J. Helicobacter pylori-induced autoimmune thyroiditis: is the pathogenic link concluded or still a hypothesis? Rev Med Microbiol 2018;29:64-72.
40. Simmonds MJ, Gough SC. Unravelling the genetic complexity of autoimmune thyroid disease: HLA, CTLA-4 and beyond. Clin Exp Immunol 2004;136:1-10.
41. Su X, Zhao Y, Li Y, Ma S, Wang Z. Gut dysbiosis is associated with primary hypothyroidism with interaction on gut-thyroid axis. Clin Sci (Lond) 2020;134:1521-1535.
42. El-Zawawy HT, Ahmed SM, El-Attar EA, Ahmed AA, Roshdy YS, Header DA. Study of gut microbiome in Egyptian patients with autoimmune thyroid diseases. Int J Clin Pract 2021;75(5):e14038.
43. Bassi V, Marino G, Iengo A, Fattoruso O, Santinelli C. Autoimmune thyroid diseases and Helicobacter pylori: the correlation is present only in Graves's disease. World J Surg 2012;18:1093.
44. Völzke H, Werner A, Guertler L, Robinson D, Wallaschofski H, John U. Putative association between anti-Borrelia IgG and autoimmune thyroid disease? Thyroid 2005;15:1273-1277.
45. Kiseleva E, Mikhailopulo K, Sviridov O, Novik G, Knirel Y, Szwajcer Dey E. The role of components of Bifidobacterium and Lactobacillus in pathogenesis and serologic diagnosis of autoimmune thyroid diseases. Benef Microbes 2011;2:139-154.
46. Yang M, Sun B, Li J, Yang B, Xu J, Zhou X, et al. Alteration of the intestinal flora may participate in the development of Graves' disease: a study conducted among the Han population in southwest China. Endocr Connect 2019;8:822-828.
47. Yan HX, An WC, Chen F, An B, Pan Y, Jin J, et al.
Intestinal microbiota changes in Graves' disease: a prospective clinical study. Biosci Rep 2020;40(9):BSR20191242.
48. Ishaq HM, Mohammad IS, Shahzad M, Ma C, Raza MA, Wu X, et al. Molecular Alteration Analysis of Human Gut Microbial Composition in Graves' disease Patients. Int J Biol Sci 2018;14:1558-1570.
49. Cornejo-Pareja I, Ruiz-Limón P, Gómez-Pérez AM, Molina-Vega M, Moreno-Indias I, Tinahones FJ. Differential Microbial Pattern Description in Subjects with Autoimmune-Based Thyroid Diseases: A Pilot Study. J Pers Med 2020;10:192.
50. Omidan N, Zahir ST, Fateh A. Cytological and Pathological Evaluation of Hashimoto's Thyroiditis. Maedica (Bucur) 2019;14:98-103.
51. Ragusa F, Fallahi P, Elia G, Gonnella D, Paparo SR, Giusti C, et al. Hashimotos' thyroiditis: Epidemiology, pathogenesis, clinic and therapy. Best Pract Res Clin Endocrinol Metab 2019;33:101367.
52. Mincer DL, Jialal I. Hashimoto Thyroiditis. StatPearls. Treasure Island (FL)2022.
53. Antonelli A, Ferrari SM, Corrado A, Di Domenicantonio A, Fallahi P. Autoimmune thyroid disorders. Autoimmun Rev 2015;14:174-180.
54. Ferri C, Sebastiani M, Giuggioli D, Colaci M, Fallahi P, Piluso A, et al. Hepatitis C virus syndrome: A constellation of organ- and non-organ specific autoimmune disorders, B-cell non-Hodgkin's lymphoma, and cancer. World J Hepatol 2015;7:327-343.
55. Tomer Y, Davies TF. Searching for the autoimmune thyroid disease susceptibility genes: from gene mapping to gene function. Endocr Rev 2003;24:694-717.
56. Tomer Y, Menconi F. Interferon induced thyroiditis. Best Pract Res Clin Endocrinol Metab 2009;23:703-712.
57. Su X, Zhao Y, Li Y, Ma S, Wang Z. Gut dysbiosis is associated with primary hypothyroidism with interaction on gut-thyroid axis. Clin Sci 2020;134:1521-1535.
58. Zhao H, Yuan L, Zhu D, Sun B, Du J, Wang J. Alterations and mechanism of gut microbiota in graves’ disease and hashimoto’s thyroiditis. Pol J Microbiol 2022;71:173.
59. Zhao F, Feng J, Li J, Zhao L, Liu Y, Chen H, et al. Alterations of the gut microbiota in Hashimoto's thyroiditis patients. Thyroid 2018;28:175-186.
60. 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.
61. Aghili R, Jafarzadeh F, Ghorbani R, Khamseh ME, Salami MA, Malek M. The association of Helicobacter pylori infection with Hashimoto's thyroiditis. Acta Medica Iranica 2013;51:293-296.
62. Bassi V, Santinelli C, Iengo A, Romano C. Identification of a correlation between Helicobacter pylori infection and Graves’ disease. Helicobacter 2010;15:558-562.
63. Franceschi F, Satta MA, Mentella MC, Penland R, Candelli M, Grillo RL, et al. Helicobacter pylori infection in patients with Hashimoto's thyroiditis. Helicobacter 2004;9:369.
64. Shmuely H, Shimon I, Gitter LA. Helicobacter pylori infection in women with Hashimoto thyroiditis: A case-control study. Medicine (Baltimore) 2016;95(29):e4074.
65. Gallo D, Piantanida E, Gallazzi M, Bartalena L, Tanda ML, Bruno A, et al. Immunological Drivers in Graves' Disease: NK Cells as a Master Switcher. Front Endocrinol (Lausanne) 2020;11:406.
66. Li H, Li J. Thyroid disorders in women. Minerva Med 2015;106:109-114.
67. Bartalena L, Tanda ML. Graves' ophthalmopathy. N Engl J Med 2009;360:994-1001.
68. Antonelli A, Ferrari SM, Ragusa F, Elia G, Paparo SR, Ruffilli I, et al. Graves' disease: Epidemiology, genetic and environmental risk factors and viruses. Best Pract Res Clin Endocrinol Metab 2020;34:101387.
69. Masetti G, Moshkelgosha S, Köhling H-L, Covelli D, Banga JP, Berchner-Pfannschmidt U, et al. Gut microbiota in experimental murine model of Graves’ orbitopathy established in different environments may modulate clinical presentation of disease. Microbiome 2018;6:1-15.
70. Zheng D, Liao H, Chen S, Liu X, Mao C, Zhang C, et al. Elevated Levels of Circulating Biomarkers Related to Leaky Gut Syndrome and Bacterial Translocation Are Associated With Graves' Disease. Front Endocrinol (Lausanne) 2021;12:796212.
71. Su X, Yin X, Liu Y, Yan X, Zhang S, Wang X, et al. Gut dysbiosis contributes to the imbalance of Treg and Th17 cells in Graves’ disease patients by propionic acid. J Clin Endocrinol Metab 2020;105:3526-3547.
72. Yang M, Li F, Zhang R, Wu Y, Yang Q, Wang F, et al. Alteration of the Intestinal Microbial Flora and the Serum IL-17 Level in Patients with Graves' Disease Complicated with Vitamin D Deficiency. Int Arch Allergy Immunol 2022;183:225-2234.
73. Jiang W, Yu X, Kosik RO, Song Y, Qiao T, Tong J, et al. Gut Microbiota May Play a Significant Role in the Pathogenesis of Graves' Disease. Thyroid 2021;31:810-820.
74. Shi TT, Xin Z, Hua L, Wang H, Zhao RX, Yang YL, et al. Comparative assessment of gut microbial composition and function in patients with Graves' disease and Graves' orbitopathy. J Endocrinol Invest 2021;44:297-310.
75. Jenq RR, Taur Y, Devlin SM, Ponce DM, Goldberg JD, Ahr KF, et al. Intestinal Blautia Is Associated with Reduced Death from Graft-versus-Host Disease. Biol Blood Marrow Transplant 2015;21:1373-1383.
76. Shi TT, Xin Z, Hua L, Zhao RX, Yang YL, Wang H, et al. Alterations in the intestinal microbiota of patients with severe and active Graves' orbitopathy: a cross-sectional study. J Endocrinol Invest 2019;42:967-978.
77. Chen J, Wang W, Guo Z, Huang S, Lei H, Zang P, et al. Associations between gut microbiota and thyroidal function status in Chinese patients with Graves’ disease. J Endocrinol Invest 2021;44:1913-1926.
78. Aschebrook‐Kilfoy B, Shu XO, Gao YT, Ji BT, Yang G, Li HL, et al. Thyroid cancer risk and dietary nitrate and nitrite intake in the Shanghai women's health study. Int J Cancer 2013;132:897-904.
79. Samimi H, Haghpanah V. Gut Microbiome and Radioiodine-Refractory Papillary Thyroid Carcinoma Pathophysiology. Trends Endocrinol Metab 2020;31:627-630.
80. Zhang J, Zhang F, Zhao C, Xu Q, Liang C, Yang Y, et al. Dysbiosis of the gut microbiome is associated with thyroid cancer and thyroid nodules and correlated with clinical index of thyroid function. Endocrine 2019;64:564-574.
81. Feng J, Zhao F, Sun J, Lin B, Zhao L, Liu Y, et al. Alterations in the gut microbiota and metabolite profiles of thyroid carcinoma patients. Int J cancer 2019;144:2728-2745.
82. Park SJ, Kim M, Jeong S, et al. Association Between Antibiotic Exposure and Thyroid Cancer: A Nationwide Cohort Study in South Korea. Thyroid 2024;34:112-122.
83. Yu X, Jiang W, Kosik RO, Song Y, Luo Q, Qiao T, et al. Gut microbiota changes and its potential relations with thyroid carcinoma. J Adv Res 2022;35:61-70.
84. Dai D, Yang Y, Yang Y, Dang T, Xiao J, Wang W, et al. Alterations of thyroid microbiota across different thyroid microhabitats in patients with thyroid carcinoma. J Transl Med 2021;19:488.
85. Ishaq HM, Mohammad IS, Hussain R, Parveen R, Shirazi JH, Fan Y, et al. Gut-Thyroid axis: How gut microbial dysbiosis associated with euthyroid thyroid cancer. J Cancer 2022;13:2014.
86. Jiang W, Lu G, Gao D, Lv Z, Li D. The relationships between the gut microbiota and its metabolites with thyroid diseases. Front Endocrinol 2022;13:943408.
87. Lu G, Yu X, Jiang W, Luo Q, Tong J, Fan S, et al. Alterations of Gut Microbiome and Metabolite Profiles Associated With Anabatic Lipid Dysmetabolism in Thyroid Cancer. Front Endocrinol 2022;13: 893164.
88. Wang M, Zhu Y. Gut microbiome versus thyroid cancer: Association and clinical implications (Review). Oncol Lett 2025;30:368.
89. Liu CJ, Chen SQ, Zhang SY, Wang JL, Tang XD, Yang KX, et al. The comparison of microbial communities in thyroid tissues from thyroid carcinoma patients. J Microbiol 2021;59:988-1001.
90. Quan Z, Zhang X, Wang S, Meng Y. Causal analysis of the gut microbiota in differentiated thyroid carcinoma: a two-sample Mendelian randomization study. Front Genet 2023;14:1299930.
91. Zheng L, Zhang L, Tang L, Huang D, Pan D, Guo W, et al. Gut microbiota is associated with response to 131I therapy in patients with papillary thyroid carcinoma. Eur J Nucl Med Mol Imaging 2023;50:1453-1465.
92. Aghajani MJ, Cooper A, McGuire H, Jeffries T, Saab J, Ismail K, et al. Pembrolizumab for anaplastic thyroid cancer: a case study. Cancer Immunol Immunother 2019;68:1921-34.
93. Karimi M, Rabiei R, Kazemi K, Motlagh RB, Asbaghi O. Effects of probiotics and synbiotics oral supplementation on thyroid function in adults: a grade-assessed systematic review and meta-analysis. Thyroid Res 2025;18:39.
94. Baurhoo B, Phillip L, Ruiz-Feria C. Effects of purified lignin and mannan oligosaccharides on intestinal integrity and microbial populations in the ceca and litter of broiler chickens. Poul Sci 2007;86:1070-1078.
95. Voicu SN, Scărlătescu AIA, Apetroaei MM, Nedea MII, Blejan IE, Udeanu DI, et al. Evaluation of Neuro-Hormonal Dynamics after the Administration of Probiotic Microbial Strains in a Murine Model of Hyperthyroidism. Nutrients 2024;16:1077.
96. Zhu X, Zhang C, Feng S, He R, Zhang S. Intestinal microbiota regulates the gut-thyroid axis: the new dawn of improving Hashimoto thyroiditis. Clin Exp Med 2024;24:39.
97. Osowiecka K, Skrypnik D, Myszkowska-Ryciak J. Assessment of the Impact of Nutritional Intervention with the Probiotic Lactiplantibacillus plantarum 299v on Nutritional Status and Quality of Life of Hashimoto's Thyroiditis Patients-A Randomized Double-Blind Study Protocol. J Pers Med 2023;13:1659.
98. Ramezani M, Reisian M, Sajadi Hezaveh Z. The effect of synbiotic supplementation on hypothyroidism: A randomized double-blind placebo controlled clinical trial. PLoS One 2023;18(2):e0277213.
99. Shu Q, Kang C, Li J, Hou Z, Xiong M, Wang X, et al. Effect of probiotics or prebiotics on thyroid function: A meta-analysis of eight randomized controlled trials. PLoS One 2024;19(1):e0296733.
100. Cheng H, Liu J, Tan Y, Feng W, Peng C. Interactions between gut microbiota and berberine, a necessary procedure to understand the mechanisms of berberine. J Pharm Anal 2022;12:541-55.
101. Yang F, Gao R, Luo X, Liu R, Xiong D. Berberine influences multiple diseases by modifying gut microbiota. Front Nutr 2023;10:1187718.
| Files | ||
| Issue | Vol 18 No 2 (2026) | |
| Section | Review Article(s) | |
| Keywords | ||
| Thyroid function Thyroid disease Microbiome Dysbiosis | ||
| Rights and permissions | |
|
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
How to Cite
1.
Karimi Behnagh A, Bourbour M, Moghaddam Shiri S, Asadi O, Honardoost M. Microbiome and thyroid diseases: future precision studies of the gut-thyroid axis to facilitate the adjuvant treatment. Iran J Microbiol. 2026;18(2):172-185.
