{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T15:31:57Z","timestamp":1781796717028,"version":"3.54.5"},"reference-count":33,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T00:00:00Z","timestamp":1763596800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Zhejiang Science and Technology Plan for Disease Prevention and Control","award":["2025JK158"],"award-info":[{"award-number":["2025JK158"]}]},{"name":"Zhejiang Science and Technology Plan for Disease Prevention and Control","award":["2025JK151"],"award-info":[{"award-number":["2025JK151"]}]},{"name":"Zhejiang Provincial Project for Medical Research and Health Sciences","award":["2025KY758"],"award-info":[{"award-number":["2025KY758"]}]},{"name":"Zhejiang Provincial Project for Medical Research and Health Sciences","award":["2024KY910"],"award-info":[{"award-number":["2024KY910"]}]},{"name":"Research Project of Zhejiang Provincial Bureau of Statistics","award":["25TJYX05"],"award-info":[{"award-number":["25TJYX05"]}]},{"name":"Zhejiang Province Traditional Chinese Medicine Science and Technology Plan Project","award":["2025ZL254"],"award-info":[{"award-number":["2025ZL254"]}]},{"name":"Zhejiang CDC Science and Technology Talent Incubation Project","award":["2023-B-04"],"award-info":[{"award-number":["2023-B-04"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Subclinical hypothyroidism (SCH) is a condition characterized by thyroid hormone dysregulation, often associated with subtle clinical symptoms and metabolic disturbances. Emerging evidence suggests that the gut microbiota plays a crucial role in modulating thyroid function, but the microbiota\u2013thyroid axis in SCH remains poorly understood. This study systematically investigates the gut microbiota composition, functional characteristics, and their correlation with thyroid hormone profiles in SCH patients. Using metagenomic sequencing and thyroid function assessments, we identified significant alterations in the gut microbiota of SCH patients, including a depletion of beneficial microbes such as Blautia and Bifidobacterium, and an enrichment of opportunistic pathogens like Bacteroides and Escherichia. Notably, Blautia depletion was negatively correlated with TSH levels, while Bacteroides abundance positively correlated with TSH levels, further highlighting the role of gut microbiota in thyroid dysfunction. Moreover, functional gene analysis revealed significant alterations in microbial metabolic pathways, with key pathways demonstrating correlations with thyroid hormone levels (free triiodothyronine (FT3) and triiodothyronine (T3)). Our findings suggest that gut microbial dysbiosis is closely associated with SCH. The study provides novel insights into the gut\u2013thyroid axis and its role in SCH, offering new targets for early diagnosis, risk stratification, and intervention strategies in thyroid diseases.<\/jats:p>","DOI":"10.3390\/microorganisms13112643","type":"journal-article","created":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T08:59:46Z","timestamp":1763715586000},"page":"2643","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Metagenomic Analysis of Gut Microbiota Structure and Function in Adults with Subclinical Hypothyroidism: A Cross-Sectional Study in China"],"prefix":"10.3390","volume":"13","author":[{"given":"Xueqing","family":"Li","sequence":"first","affiliation":[{"name":"Zhejiang Provincial Center for Disease Control and Prevention, 3399 Bin Sheng Road, Binjiang District, Hangzhou 310051, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Ma","sequence":"additional","affiliation":[{"name":"Zhejiang Provincial Center for Disease Control and Prevention, 3399 Bin Sheng Road, Binjiang District, Hangzhou 310051, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3013-1434","authenticated-orcid":false,"given":"Lizhi","family":"Wu","sequence":"additional","affiliation":[{"name":"Zhejiang Provincial Center for Disease Control and Prevention, 3399 Bin Sheng Road, Binjiang District, Hangzhou 310051, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0375-509X","authenticated-orcid":false,"given":"Zhe","family":"Mo","sequence":"additional","affiliation":[{"name":"Zhejiang Provincial Center for Disease Control and Prevention, 3399 Bin Sheng Road, Binjiang District, Hangzhou 310051, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7165-3613","authenticated-orcid":false,"given":"Zhijian","family":"Chen","sequence":"additional","affiliation":[{"name":"Zhejiang Provincial Center for Disease Control and Prevention, 3399 Bin Sheng Road, Binjiang District, Hangzhou 310051, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronghua","family":"Zhang","sequence":"additional","affiliation":[{"name":"Zhejiang Provincial Center for Disease Control and Prevention, 3399 Bin Sheng Road, Binjiang District, Hangzhou 310051, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingluan","family":"Xing","sequence":"additional","affiliation":[{"name":"Zhejiang Provincial Center for Disease Control and Prevention, 3399 Bin Sheng Road, Binjiang District, Hangzhou 310051, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"12","DOI":"10.5455\/medarh.2022.76.12-16","article-title":"Hypothyroidism and Subclinical Hypothyroidism as a Consequence of COVID-19 Infection","volume":"76","author":"Burekovic","year":"2022","journal-title":"Med. Arch."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"itc1","DOI":"10.7326\/AITC202007070","article-title":"Hypothyroidism","volume":"173","author":"McDermott","year":"2020","journal-title":"Ann. Intern. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"101367","DOI":"10.1016\/j.beem.2019.101367","article-title":"Hashimotos\u2019 thyroiditis: Epidemiology, pathogenesis, clinic and therapy","volume":"33","author":"Ragusa","year":"2019","journal-title":"Best Pract. Res. Clin. Endocrinol. Metab."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1552","DOI":"10.1056\/NEJMra1510030","article-title":"Graves\u2019 Disease","volume":"375","author":"Smith","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"641","DOI":"10.7326\/M15-0483","article-title":"Screening for thyroid dysfunction: U.S. Preventive Services Task Force recommendation statement","volume":"162","author":"LeFevre","year":"2015","journal-title":"Ann. Intern. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1001\/jama.2019.9052","article-title":"Subclinical Hypothyroidism: A Review","volume":"322","author":"Biondi","year":"2019","journal-title":"JAMA"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"17","DOI":"10.2165\/11598070-000000000-00000","article-title":"Overt and subclinical hypothyroidism: Who to treat and how","volume":"72","author":"Khandelwal","year":"2012","journal-title":"Drugs"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1007\/s42000-020-00208-8","article-title":"Relationship of thyroid dysfunction with cardiovascular diseases: Updated review on heart failure progression","volume":"19","author":"Gouda","year":"2020","journal-title":"Hormones"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1550","DOI":"10.1016\/S0140-6736(17)30703-1","article-title":"Hypothyroidism","volume":"390","author":"Chaker","year":"2017","journal-title":"Lancet"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"3306","DOI":"10.1210\/jc.2017-00986","article-title":"Thyroid Function, Cardiovascular Risk Factors, and Incident Atherosclerotic Cardiovascular Disease: The Atherosclerosis Risk in Communities (ARIC) Study","volume":"102","author":"Martin","year":"2017","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Bastos, D.C.d.S., Chiamolera, M.I., Silva, R.E., de Souza, M.D.C.B., Antunes, R.A., Souza, M.M., Mancebo, A.C.A., Ar\u00eaas, P.C.F., Reis, F.M., and Turco, E.G.L. (2023). Metabolomic analysis of follicular fluid from women with Hashimoto thyroiditis. Sci. Rep., 13.","DOI":"10.1038\/s41598-023-39514-7"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e230041","DOI":"10.1530\/ETJ-23-0041","article-title":"Neonatal screening for primary and central congenital hypothyroidism: Is it time to go Dutch?","volume":"12","author":"Boelen","year":"2023","journal-title":"Eur. Thyroid J."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1007\/s11745-003-1038-4","article-title":"Sedentary lifestyle and risk of obesity and type 2 diabetes","volume":"38","author":"Hu","year":"2003","journal-title":"Lipids"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/j.copbio.2012.08.005","article-title":"Bacteria as vitamin suppliers to their host: A gut microbiota perspective","volume":"24","author":"LeBlanc","year":"2013","journal-title":"Curr. Opin. Biotechnol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.phrs.2012.10.007","article-title":"Modulation of intestinal barrier by intestinal microbiota: Pathological and therapeutic implications","volume":"69","author":"Natividad","year":"2013","journal-title":"Pharmacol. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1152\/physrev.00045.2009","article-title":"Gut microbiota in health and disease","volume":"90","author":"Sekirov","year":"2010","journal-title":"Physiol. Rev."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1089\/thy.2022.0491","article-title":"A Comprehensive Review of Thyroid Hormone Metabolism in the Gut and Its Clinical Implications","volume":"33","author":"Fenneman","year":"2023","journal-title":"Thyroid"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Knezevic, J., Starchl, C., Tmava Berisha, A., and Amrein, K. (2020). Thyroid-Gut-Axis: How Does the Microbiota Influence Thyroid Function?. Nutrients, 12.","DOI":"10.3390\/nu12061769"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1089\/thy.2019.0067","article-title":"Efficacy and Safety of Long-Term Universal Salt Iodization on Thyroid Disorders: Epidemiological Evidence from 31 Provinces of Mainland China","volume":"30","author":"Li","year":"2020","journal-title":"Thyroid"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Segata, N., Izard, J., Waldron, L., Gevers, D., Miropolsky, L., Garrett, W.S., and Huttenhower, C. (2011). Metagenomic biomarker discovery and explanation. Genome. Biol., 12.","DOI":"10.1186\/gb-2011-12-6-r60"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e21463","DOI":"10.1016\/j.heliyon.2023.e21463","article-title":"Integrated microbiome and metabolome analysis reveals a distinct microbial and metabolic signature in Graves\u2019 disease and hypothyroidism","volume":"9","author":"Jiang","year":"2023","journal-title":"Heliyon"},{"key":"ref_22","first-page":"138","article-title":"Cicatricial stenosis of the stomach and small intestine after a chemical burn","volume":"11","author":"Smirnov","year":"1984","journal-title":"Khirurgiia"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.immuni.2013.12.007","article-title":"Activation of Gpr109a, receptor for niacin and the commensal metabolite butyrate, suppresses colonic inflammation and carcinogenesis","volume":"40","author":"Singh","year":"2014","journal-title":"Immunity"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1007\/s12011-010-8734-x","article-title":"Preparation of selenium\/zinc-enriched probiotics and their effect on blood selenium and zinc concentrations, antioxidant capacities, and intestinal microflora in canine","volume":"141","author":"Ren","year":"2011","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1016\/j.tem.2019.05.008","article-title":"Microbiota and Thyroid Interaction in Health and Disease","volume":"30","author":"Wahl","year":"2019","journal-title":"Trends. Endocrinol. Metab."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Xie, L., Zhao, H., and Chen, W. (2023). Relationship between gut microbiota and thyroid function: A two-sample Mendelian randomization study. Front. Endocrinol., 14.","DOI":"10.3389\/fendo.2023.1240752"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1016\/j.biopha.2017.08.101","article-title":"Molecular estimation of alteration in intestinal microbial composition in Hashimoto\u2019s thyroiditis patients","volume":"95","author":"Ishaq","year":"2017","journal-title":"Biomed. Pharmacother."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1089\/thy.2020.0193","article-title":"Gut Microbiota May Play a Significant Role in the Pathogenesis of Graves\u2019 Disease","volume":"31","author":"Jiang","year":"2021","journal-title":"Thyroid"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Mendoza-Le\u00f3n, M.J., Mangalam, A.K., Regaldiz, A., Gonz\u00e1lez-Madrid, E., Rangel-Ram\u00edrez, M.A., \u00c1lvarez-Mardonez, O., Vallejos, O.P., M\u00e9ndez, C., Bueno, S.M., and Melo-Gonz\u00e1lez, F. (2023). Gut microbiota short-chain fatty acids and their impact on the host thyroid function and diseases. Front. Endocrinol., 14.","DOI":"10.3389\/fendo.2023.1192216"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1055\/s-0028-1094095","article-title":"Effect of changing intestinal bacterial flora on thyroid function in the rat","volume":"4","author":"Vought","year":"1972","journal-title":"Horm. Metab. Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1846","DOI":"10.1210\/me.2010-0102","article-title":"NF-kappaB p65 subunit mediates lipopolysaccharide-induced Na(+)\/I(-) symporter gene expression by involving functional interaction with the paired domain transcription factor Pax8","volume":"24","author":"Nicola","year":"2010","journal-title":"Mol. Endocrinol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3260","DOI":"10.1210\/en.2005-0789","article-title":"Bacterial lipopolysaccharide stimulates the thyrotropin-dependent thyroglobulin gene expression at the transcriptional level by involving the transcription factors thyroid transcription factor-1 and paired box domain transcription factor 8","volume":"147","author":"Costamagna","year":"2006","journal-title":"Endocrinology"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1210\/en.2008-0345","article-title":"Functional toll-like receptor 4 conferring lipopolysaccharide responsiveness is expressed in thyroid cells","volume":"150","author":"Nicola","year":"2009","journal-title":"Endocrinology"}],"container-title":["Microorganisms"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2607\/13\/11\/2643\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T09:25:45Z","timestamp":1763717145000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2607\/13\/11\/2643"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,20]]},"references-count":33,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2025,11]]}},"alternative-id":["microorganisms13112643"],"URL":"https:\/\/doi.org\/10.3390\/microorganisms13112643","relation":{},"ISSN":["2076-2607"],"issn-type":[{"value":"2076-2607","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,20]]}}}