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Dysbiosis of the gut microbiome is associated with thyroid cancer and thyroid nodules and correlated with clinical index of thyroid function

  • Jiaming Zhang
  • Fanghua Zhang
  • Changying Zhao
  • Qian Xu
  • Cheng Liang
  • Ying Yang
  • Huiling Wang
  • Yongfang Shang
  • Ye Wang
  • Xiaofeng Mu
  • Dequan Zhu
  • Chunling Zhang
  • Junjie YangEmail author
  • Minxiu YaoEmail author
  • Lei ZhangEmail author
Original Article



Thyroid cancer and thyroid nodules are the most prevalent form of thyroid endocrine disorder. The balance of gut microbiome is highly crucial for a healthy human body, especially for the immune and endocrine system. However, the relationship between gut microbiome and the thyroid endocrine disorders such as thyroid cancer and thyroid nodules has not been reported yet.


A cohort of 74 patients was recruited for this study. Among them, 20 patients had thyroid cancer, 18 patients had thyroid nodules, and 36 were matched healthy controls. Gut microbiome composition was analyzed by 16S rRNA (16S ribosomal RNA) gene-based sequencing protocol.


We compared the gut microbiome results of 74 subjects and established the correlation between gut microbiome and thyroid endocrine function for both thyroid cancer and thyroid nodules. The results inferred that alpha and beta diversity were different for patients with thyroid tumor than the healthy controls (p < 0.01). In comparison to healthy controls, the relative abundance of Neisseria (p < 0.001) and Streptococcus (p < 0.001) was significantly higher for thyroid cancer and thyroid nodules. Butyricimonas (p < 0.001) and Lactobacillus (p < 0.001) displayed notably lower relative abundance for thyroid cancer and thyroid nodules, respectively. It was also found that the clinical indexes were correlated with gut microbiome.


Our results indicate that both thyroid cancer and thyroid nodules are associated with the composition of gut microbiome. These results may support further clinical diagnosis to a great extent and help in developing potential probiotics to facilitate the treatment of thyroid cancer and thyroid nodules.


Gut microbiome Thyroid cancer Thyroid nodules 16S rRNA gene sequencing Clinical index 





Thyroglobulin antibody


Thyroid stimulating hormone


Free triiodothyronine


Free tetraiodothyronine


Thyrotropin receptor antibody


Thyroid peroxidase antibody



This study was supported by the National Natural Science Foundation of China under contract No.31471202 (Lei Zhang) and No. 81670822 (Ye Wang); the Shandong Provincial Key Research and Development Program under contract No. 2016YYSP009 (Lei Zhang); Weihai Technique Extension Project under contract No. 2016GNS023 (Lei Zhang). Qingdao Key Research Project No. 17-3-3-10-nsh (Chunling Zhang). Lei Zhang was also supported by the Taishan Scholars Program of Shandong Province (No. tshw20120206).

Author Contributions

L.Z., J.Y. and M.Y. designed the study. J.Z., C.L., Y.Y., H.W., Y.S., Y.W., X.M., D.Z., and C.Z. performed measurements and data analysis. C.Z. and Q.X. obtained samples. F.Z., J.Z. and L.Z. wrote the manuscript. All authors have read and critically revised the manuscript.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest. The authors have nothing to disclose.

Ethical approval

All procedures performed in the above studies involving human participants were in accordance with the ethical standards of the institution and/or national research committee and with the 1964 Declaration of Helsinki along with its later amendments or comparable ethical standards.

Informed consent

All the subjects signed informed consent beforehand and belonged to the same geographical area. Data was collected by using a standardized questionnaire including basic information, medical history and examination results.


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Authors and Affiliations

  1. 1.Qingdao Human Microbiome CenterThe Affiliated Central Hospital of Qingdao UniversityQingdaoChina
  2. 2.College of Life ScienceShandong Normal UniversityJinanChina
  3. 3.Department of EndocrinologyThe Affiliated Central Hospital of Qingdao UniversityQingdaoChina
  4. 4.School of Information Science and EngineeringShandong Normal UniversityJinanChina
  5. 5.Clinical Laboratory and Core Research LaboratoryThe Affiliated Central Hospital of Qingdao UniversityQingdao 266042China
  6. 6.Microbiological LaboratoryLin Yi People’s HospitalLinyi 276003China
  7. 7.College of Life ScienceQilu Normal UniversityJinanChina
  8. 8.Shandong Children’s Microbiome CenterQilu Children’s Hospital of Shandong UniversityJinanChina
  9. 9.Shandong Institutes for Food and Drug Control, Xinluo Street 2749JinanChina
  10. 10.Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, School of Chemistry and EnvironmentBeihang UniversityBeijingChina

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