Abstract
Studies analyzing the relationship between microbiota composition and the thyroid have been increasing rapidly in recent years, and evidence has recently come to light about the involvement of the gut microbiota in various aspects of thyroid pathology. Recently, besides studies analyzing the microbiota composition of different biological niches (salivary microbiota or thyroid tumor microenvironment) in patients with thyroid disorders, some studies have been carried out in peculiar subcategories of patients (pregnant women or obese). Other studies added a metabolomic insight into the characterization of fecal microflora in an attempt to enlighten specific metabolic pathways that could be involved in thyroid disorder pathogenesis. Lastly, some studies described the use of probiotics or symbiotic supplementation aimed at modulating gut microbiota composition for therapeutic purposes. The aim of this systematic review is to analyze the last advancements in the relationship between gut microbiota composition and thyroid autoimmunity, extending the analysis also to nonautoimmune thyroid disorders as well as to the characterization of the microbiota belonging to different biological niches in these patients. The overall results of the present review article strengthen the existence of a bidirectional relationship between the intestine, with its microbial set, and thyroid homeostasis, thus supporting the newly recognized entity known as the gut-thyroid axis.
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References
An Y, Zhang W, Liu T et al (2021) The intratumoural microbiota in cancer: new insights from inside. Biochim Biophys Acta Rev Cancer 1876(2):188626. https://doi.org/10.1016/j.bbcan.2021.188626
Bargiel P, Szczuko M, Stachowska L et al (2021) Microbiome metabolites and thyroid dysfunction. J Clin Med 10(16):3609. https://doi.org/10.3390/jcm10163609
Benvenga S, Guarneri F (2016) Molecular mimicry and autoimmune thyroid disease. Rev Endocr Metab Disord 17(4):485–498. https://doi.org/10.1007/s11154-016-9363-2
Bullman S, Pedamallu CS, Sicinska E et al (2017) Analysis of fusobacterium persistence and antibiotic response in colorectal cancer. Science 358(6369):1443–1448. https://doi.org/10.1126/science.aal5240
Cai Y, Xu Y, Ban Y et al (2022) Plasma lipid profile and intestinal microflora in pregnancy women with hypothyroidism and their correlation with pregnancy outcomes. Front Endocrinol (Lausanne) 12:792536. https://doi.org/10.3389/fendo.2021.792536
Cayres LCF, de Salis LVV, Rodrigues GSP et al (2021) Detection of alterations in the gut microbiota and intestinal permeability in patients with Hashimoto thyroiditis. Front Immunol 2:579140. https://doi.org/10.3389/fimmu.2021.579140
Chang SC, Lin SF, Chen ST et al (2021) Alterations of gut microbiota in patients with Graves’ disease. Front Cell Infect Microbiol 11:663131. https://doi.org/10.3389/fcimb.2021.663131
Chen J, Wright K, Davis JM et al (2016) An expansion of rare lineage intestinal microbes characterizes rheumatoid arthritis. Genome Med 8(1):43. https://doi.org/10.1186/s13073-016-0299-7
Chen B, Sun L, Zhang X (2017) Integration of microbiome and epigenome to decipher the pathogenesis of autoimmune diseases. J Autoimmun 83:31–42. https://doi.org/10.1016/j.jaut.2017.03.009
Chen J, Chen X, Ho CL (2021a) Recent development of probiotic Bifidobacteria for treating human diseases. Front Bioeng Biotechnol 9:770248. https://doi.org/10.3389/fbioe.2021.770248
Chen J, Wang W, Guo Z et al (2021b) Associations between gut microbiota and thyroidal function status in Chinese patients with Graves’ disease. J Endocrinol Investig 44(9):1913–1926. https://doi.org/10.1007/s40618-021-01507-6
Chow JC, Young DW, Golenbock DT et al (1999) Toll-like receptor-4 mediates lipopolysaccharide-induced signal transduction. J Biol Chem 274(16):10689–10692. https://doi.org/10.1074/jbc.274.16.10689
Cornejo-Pareja I, Ruiz-Limón P, Gómez-Pérez AM et al (2020) Differential microbial pattern description in subjects with autoimmune-based thyroid diseases: a pilot study. J Pers Med 10(4):192. https://doi.org/10.3390/jpm10040192
Dai D, Yang Y, Yang Y et al (2021) Alterations of thyroid microbiota across different thyroid microhabitats in patients with thyroid carcinoma. J Transl Med 19(1):488. https://doi.org/10.1186/s12967-021-03167-9
de Aquino SG, Abdollahi-Roodsaz S, Koenders MI et al (2014) Periodontal pathogens directly promote autoimmune experimental arthritis by inducing a TLR2- and IL-1-driven Th17 response. J Immunol 192(9):4103–4111. https://doi.org/10.4049/jimmunol.1301970
DeClercq V, Nearing JT, Langille MGI (2021) Investigation of the impact of commonly used medications on the oral microbiome of individuals living without major chronic conditions. PLoS One 16(12):e0261032. https://doi.org/10.1371/journal.pone.0261032
Docimo G, Cangiano A, Romano RM et al (2020) The human microbiota in endocrinology: implications for pathophysiology, treatment, and prognosis in thyroid diseases. Front Endocrinol (Lausanne) 11:586529. https://doi.org/10.3389/fendo.2020.586529
Dong T, Zhao F, Yuan K et al (2021) Association between serum thyroid-stimulating hormone levels and salivary microbiome shifts. Front Cell Infect Microbiol 11:603291. https://doi.org/10.3389/fcimb.2021.603291
El-Zawawy HT, Ahmed SM, El-Attar EA et al (2021) Study of gut microbiome in Egyptian patients with autoimmune thyroid diseases. Int J Clin Pract 75(5):e14038. https://doi.org/10.1111/ijcp.14038
Feng J, Zhao F, Sun J et al (2019) Alterations in the gut microbiota and metabolite profiles of thyroid carcinoma patients. Int J Cancer 144(11):2728–2745. https://doi.org/10.1002/ijc.32007
Fernández-García V, González-Ramos S, Martín-Sanz P et al (2021) Beyond classic concepts in thyroid homeostasis: immune system and microbiota. Mol Cell Endocrinol 533:111333. https://doi.org/10.1016/j.mce.2021.111333
Fröhlich E, Wahl R (2019) Microbiota and thyroid interaction in health and disease. Trends Endocrinol Metab 30(8):479–490. https://doi.org/10.1016/j.tem.2019.05.008
Gnanasekar A, Castaneda G, Iyangar A et al (2021) The intratumor microbiome predicts prognosis across gender and subtypes in papillary thyroid carcinoma. Comput Struct Biotechnol J 19:1986–1997. https://doi.org/10.1016/j.csbj.2021.03.032
Gong B, Wang C, Meng F et al (2021) Association between gut microbiota and autoimmune thyroid disease: a systematic review and meta-analysis. Front Endocrinol (Lausanne) 12:774362. https://doi.org/10.3389/fendo.2021.774362
Habtemariam S (2020) Berberine pharmacology and the gut microbiota: a hidden therapeutic link. Pharmacol Res 155:104722. https://doi.org/10.1016/j.phrs.2020.104722
Han Z, Cen C, Ou Q et al (2022) The potential prebiotic Berberine combined with Methimazole improved the therapeutic effect of Graves’ disease patients through regulating the intestinal microbiome. Front Immunol 12:826067. https://doi.org/10.3389/fimmu.2021.826067
Harries DJ (1923) The influence of intestinal bacteria upon the thyroid gland. Br Med J 1(3248):553–555. https://doi.org/10.1136/bmj.1.3248.553
Hazenberg MP, de Herder WW, Visser TJ (1988) Hydrolysis of iodothyronine conjugates by intestinal bacteria. FEMS Microbiol Rev 4(1):9–16. https://doi.org/10.1111/j.1574-6968.1988.tb02709.x-i1
Ishaq HM, Mohammad IS, Shahzad M et al (2018) Molecular alteration analysis of human gut microbial composition in Graves’ disease patients. Int J Biol Sci 14(11):1558–1570. https://doi.org/10.7150/ijbs.24151
Ishaq HM, Mohammad IS, Hussain R et al (2022) Gut-thyroid axis: how gut microbial dysbiosis associated with euthyroid thyroid cancer. J Cancer 13(6):2014–2028
Jeong JY, Kim TB, Kim J et al (2020) Diversity in the extracellular vesicle-derived microbiome of tissues according to tumor progression in pancreatic cancer. Cancers (Basel) 12(9):2346. https://doi.org/10.3390/cancers12092346
Jiang W, Yu X, Kosik RO et al (2021) Gut microbiota may play a significant role in the pathogenesis of Graves’ disease. Thyroid 31(5):810–820. https://doi.org/10.1089/thy.2020.0193
Kiseleva EP, Mikhailopulo KI, Sviridov OV et al (2011) The role of components of Bifidobacterium and Lactobacillus in pathogenesis and serologic diagnosis of autoimmune thyroid diseases. Benefic Microbes 2(2):139–154. https://doi.org/10.3920/BM2010.0011
Köhling HL, Plummer SF, Marchesi JR et al (2017) The microbiota and autoimmunity: their role in thyroid autoimmune diseases. Clin Immunol 183:63–74. https://doi.org/10.1016/j.clim.2017.07.001
Lauritano EC, Bilotta AL, Gabrielli M et al (2007) Association between hypothyroidism and small intestinal bacterial overgrowth. J Clin Endocrinol Metab 92:4180e4
Li A, Li T, Gao X et al (2021) Gut microbiome alterations in patients with thyroid nodules. Front Cell Infect Microbiol 11:643968. https://doi.org/10.3389/fcimb.2021.643968
Li J, Xu Y, Cai Y et al (2022) Association of differential metabolites with small intestinal microflora and maternal outcomes in subclinical hypothyroidism during pregnancy. Front Cell Infect Microbiol 11:779659. https://doi.org/10.3389/fcimb.2021.779659
Lin B, Zhao F, Liu Y et al (2022) Randomized clinical trial: probiotics alleviated oral-gut microbiota dysbiosis and thyroid hormone withdrawal-related complications in thyroid cancer patients before radioiodine therapy following thyroidectomy. Front Endocrinol (Lausanne) 13:834674. https://doi.org/10.3389/fendo.2022.834674
Liu S, An Y, Cao B et al (2020) The composition of gut microbiota in patients bearing Hashimoto’s thyroiditis with euthyroidism and hypothyroidism. Int J Endocrinol 2020:5036959
Liu CJ, Chen SQ, Zhang SY et al (2021) The comparison of microbial communities in thyroid tissues from thyroid carcinoma patients. J Microbiol 59(11):988–1001. https://doi.org/10.1007/s12275-021-1271-9
López P, de Paz B, Rodríguez-Carrio J et al (2016) Th17 responses and natural IgM antibodies are related to gut microbiota composition in systemic lupus erythematosus patients. Sci Rep 6:24072. https://doi.org/10.1038/srep24072
Mendonça SMS, Corrêa JD, Souza AF et al (2019) Immunological signatures in saliva of systemic lupus erythematosus patients: influence of periodontal condition. Clin Exp Rheumatol 37(2):208–214
National Heart, Lung, and Blood Institute Quality Assessment Tool. https://www.nhlbi.nih.gov/health-topics/study-quality-assessment-tools. Accessed 31 May 2022
Nejman D, Livyatan I, Fuks G et al (2020) The human tumor microbiome is composed of tumor type-specific intracellular bacteria. Science 368(6494):973–980. https://doi.org/10.1126/science.aay9189
Nogal A, Valdes AM, Menni C (2021) The role of short-chain fatty acids in the interplay between gut microbiota and diet in cardio-metabolic health. Gut Microbes 13(1):1–24. https://doi.org/10.1080/19490976.2021.1897212
Page MJ, McKenzie JE, Bossuyt PM et al (2021) The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ 372:n71. https://doi.org/10.1136/bmj.n71
Patil AD (2014) Link between hypothyroidism and small intestinal bacterial overgrowth. Indian J Endocrinol Metab 18(3):307–309. https://doi.org/10.4103/2230-8210.131155
Provenzano MJ, Fitzgerald MP, Krager K et al (2007) Increased iodine uptake in thyroid carcinoma after treatment with sodium butyrate and decitabine (5-Aza-dC). Otolaryngol Head Neck Surg 137(5):722–728. https://doi.org/10.1016/j.otohns.2007.07.030
Qi X, Yun C, Pang Y et al (2021) The impact of the gut microbiota on the reproductive and metabolic endocrine system. Gut Microbes 13(1):1–21. https://doi.org/10.1080/19490976.2021.1894070
Ragusa F, Fallahi P, Elia G et al (2019) Hashimotos’ thyroiditis: epidemiology, pathogenesis, clinic and therapy. Best Pract Res Clin Endocrinol Metab 33(6):101367. https://doi.org/10.1016/j.beem.2019.101367
Richard ML, Liguori G, Lamas B et al (2018) Mucosa-associated microbiota dysbiosis in colitis associated cancer. Gut Microbes 9(2):131–142. https://doi.org/10.1080/19490976.2017.1379637
Rothschild D, Weissbrod O, Barkan E et al (2018) Environment dominates over host genetics in shaping human gut microbiota. Nature 555(7695):210–215. https://doi.org/10.1038/nature25973
Sekirov I, Russell SL, Antunes LC et al (2010) Gut microbiota in health and disease. Physiol Rev 90(3):859–904. https://doi.org/10.1152/physrev.00045.2009
Sepich-Poore GD, Zitvogel L, Straussman R et al (2021) The microbiome and human cancer. Science 371(6536):eab c4552. https://doi.org/10.1126/science.abc4552
Shen YW, Zhang XM, Lv M et al (2015) Utility of gonadotropin-releasing hormone agonists for prevention of chemotherapy-induced ovarian damage in premenopausal women with breast cancer: a systematic review and meta-analysis. Onco Targets Ther 8:3349–3359. https://doi.org/10.2147/OTT.S95936
Shi TT, Xin Z, Hua L et al (2019) Alterations in the intestinal microbiota of patients with severe and active Graves’ orbitopathy: a cross-sectional study. J Endocrinol Investig 42(8):967–978. https://doi.org/10.1007/s40618-019-1010-9
Shin NR, Whon TW, Bae JW (2015) Proteobacteria: microbial signature of dysbiosis in gut microbiota. Trends Biotechnol 33(9):496–503. https://doi.org/10.1016/j.tibtech.2015.06.011
Si J, Lee C, Ko G (2017) Oral microbiota: microbial biomarkers of metabolic syndrome independent of host genetic factors. Front Cell Infect Microbiol 7:516. https://doi.org/10.3389/fcimb.2017.00516
Song YC, Li D, Lyu ZW (2019) Characteristics of gut microbiota in patients with hyperthyroidism. Fudan Univ J Med Sci 46(02):19–28. https://doi.org/10.3969/j.issn.1672-8467.2019.02.003
Su X, Yin X, Liu Y et al (2020a) Gut dysbiosis contributes to the imbalance of Treg and Th17 cells in Graves’ disease patients by propionic acid. J Clin Endocrinol Metab 105:dgaa511. https://doi.org/10.1210/clinem/dgaa511
Su X, Zhao Y, Li Y et al (2020b) Gut dysbiosis is associated with primary hypothyroidism with interaction on gut-thyroid axis. Clin Sci (Lond) 134(12):1521–1535. https://doi.org/10.1042/CS20200475
Sun Y, Chen Q, Lin P et al (2019) Characteristics of gut microbiota in patients with rheumatoid arthritis in Shanghai, China. Front Cell Infect Microbiol 9:369. https://doi.org/10.3389/fcimb.2019.00369
Sun J, Zhao F, Lin B et al (2020) Gut microbiota participates in antithyroid drug induced liver injury through the lipopolysaccharide related signaling pathway. Front Pharmacol 11:598170. https://doi.org/10.3389/fphar.2020.598170
Tabasi M, Eybpoosh S, Sadeghpour Heravi F et al (2021) Gut microbiota and serum biomarker analyses in obese patients diagnosed with diabetes and hypothyroid disorder. Metab Syndr Relat Disord 19(3):144–151. https://doi.org/10.1089/met.2020.0119
Talebi S, Karimifar M, Heidari Z et al (2020a) The effect of synbiotic supplementation on anthropometric indices, appetite, and constipation in people with hypothyroidism: a randomized, double-blind, placebo-controlled trial. Phytother Res 34(10):2712–2720. https://doi.org/10.1002/ptr.6710
Talebi S, Karimifar M, Heidari Z et al (2020b) The effects of synbiotic supplementation on thyroid function and inflammation in hypothyroid patients: a randomized, double-blind, placebo-controlled trial. Complement Ther Med 48:102234. https://doi.org/10.1016/j.ctim.2019.102234
Taylor PN, Albrecht D, Scholz A et al (2018) Global epidemiology of hyperthyroidism and hypothyroidism. Nat Rev Endocrinol 14(5):301–316. https://doi.org/10.1038/nrendo.2018.18
Virili C, Centanni M (2017) “With a little help from my friends” – the role of microbiota in thyroid hormone metabolism and enterohepatic recycling. Mol Cell Endocrinol 458:39–43. https://doi.org/10.1016/j.mce.2017.01.053
Virili C, Stramazzo I, Centanni M (2021) Gut microbiome and thyroid autoimmunity. Best Pract Res Clin Endocrinol Metab 35(3):101506. https://doi.org/10.1016/j.beem.2021.101506
Wang B, Xu Y, Zhang M et al (2020) Oral and intestinal microbial features in pregnant women with hypothyroidism and their correlations with pregnancy outcomes. Am J Physiol Endocrinol Metab 319(6):E1044–E1052. https://doi.org/10.1152/ajpendo.00234.2020
Wang B, Xu Y, Hou X et al (2021) Small intestinal bacterial overgrowth in subclinical hypothyroidism of pregnant women. Front Endocrinol (Lausanne) 12:604070. https://doi.org/10.3389/fendo.2021.604070
Yan HX, An WC, Chen F et al (2020) Intestinal microbiota changes in Graves’ disease: a prospective clinical study. Biosci Rep 40(9):BSR20191242. https://doi.org/10.1042/BSR20191242
Yang M, Li F, Zhang R et al (2022a) 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 183(2):225–234. https://doi.org/10.1159/000518949
Yang M, Zheng X, Wu Y et al (2022b) Preliminary observation of the changes in the intestinal Flora of patients with Graves’ disease before and after methimazole treatment. Front Cell Infect Microbiol 12:794711. https://doi.org/10.3389/fcimb.2022.794711
Yao Z, Zhao M, Gong Y et al (2020) Relation of gut microbes and L-thyroxine through altered thyroxine metabolism in subclinical hypothyroidism subjects. Front Cell Infect Microbiol 10:495. https://doi.org/10.3389/fcimb.2020.00495
Yu X, Jiang W, Kosik RO et al (2021) Gut microbiota changes and its potential relations with thyroid carcinoma. J Adv Res 35:61–70. https://doi.org/10.1016/j.jare.2021.04.001
Zhang J, Zhang F, Zhao C et al (2019) Dysbiosis of the gut microbiome is associated with thyroid cancer and thyroid nodules and correlated with clinical index of thyroid function. Endocrine 64(3):564–574. https://doi.org/10.1007/s12020-018-1831-x
Zheng D, Liao H, Chen S et al (2021) Elevated levels of circulating biomarkers related to leaky gut syndrome and bacterial translocation are associated with Graves’ disease. Front Endocrinol (Lausanne) 12:796212. https://doi.org/10.3389/fendo.2021.796212
Zhou L, Li X, Ahmed A et al (2014) Gut microbe analysis between hyperthyroid and healthy individuals. Curr Microbiol 69(5):675–680. https://doi.org/10.1007/s00284-014-0640-6
Zhu Q, Hou Q, Huang S, et al (2021) Compositional and genetic alterations in Graves’ disease gut microbiome reveal specific diagnostic biomarkers. ISME J 15(11):3399–3411. https://doi.org/10.1038/s41396-021-01016-7. Erratum in: ISME J. 2022 Apr;16(4):1201
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Stramazzo, I., Capriello, S., Filardo, S., Centanni, M., Virili, C. (2023). Microbiota and Thyroid Disease: An Updated Systematic Review. In: Donelli, G. (eds) Advances in Microbiology, Infectious Diseases and Public Health. Advances in Experimental Medicine and Biology(), vol 1434. Springer, Cham. https://doi.org/10.1007/5584_2023_770
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