J Cancer 2022; 13(6):2014-2028. doi:10.7150/jca.66816 This issue

Research Paper

Gut-Thyroid axis: How gut microbial dysbiosis associated with euthyroid thyroid cancer

Hafiz Muhammad Ishaq1,2, Imran Shair Mohammad3,4, Riaz Hussain5, Rashida Parveen6, Jafir Hussain Shirazi7, Yang Fan8, Muhammad Shahzad9, Khezar Hayat10, Huan Li11, Ayesha Ihsan12, Kiran Sher Muhammad13, Muhammad Usman2,12, Siruo Zhang1, Lu Yuan1, Shakir Ullah1, Ana Cláudia Paiva-Santos14,15, Jiru Xu1✉

1. Department of Microbiology and Immunology, Key Laboratory of Environment and Genes Related to Diseases of Chinese Ministry of Education, School of Medicine, Xi'an Jiaotong University, Xi'an, China
2. Faculty of Veterinary and Animal Sciences, Muhammad Nawaz Shareef University of Agriculture Multan 66000, Pakistan
3. ERKAM-Clinical-Engineering Research and Application Center, Erciyes University, 38039, Kayseri, Turkey
4. ERFARMA-Drug Development and Implementation Center, Erciyes University, 38039, Kayseri, Turkey
5. Department of Pathology, Faculty of Veterinary and Animal Sciences, The Islamia University of Bahawalpur, Pakistan
6. Department of Pharmaceutical Sciences, Superior University, Lahore, Pakistan
7. Department of Pharmaceutics, Faculty of Pharmacy, The Islamia University of Bahawalpur, Pakistan
8. Department of Microbiology, School of Basic Medical Science, Xinxiang Medical University, Xinxiang China
9. Department of Pharmacology, University of Health Sciences, Khyaban-e-Jamia Punjab, Lahore, Pakistan
10. Institute of Pharmaceutical Sciences, University of Veterinary and Animal Sciences, Lahore, Pakistan
11. Xi'an Mental Health Centre, Xi'an China
12. National Institiute for Biotechnology and Genetic Engineering College, Pakistan Institiute Engineering and Applied Sciences (NIBGE-C, PIEAS), Faisalabad 38000, Punjab, Pakistan
13. Department of Zoology Wild-life and Fisheries, University of Agriculture, Faisalabad, Pakistan
14. Department of Pharmaceutical Technology, Faculty of Pharmacy of the University of Coimbra, University of Coimbra, Coimbra, Portugal
15. REQUIMTE/LAQV, Group of Pharmaceutical Technology, Faculty of Pharmacy of the University of Coimbra,University of Coimbra, Coimbra, Portugal

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Ishaq HM, Mohammad IS, Hussain R, Parveen R, Shirazi JH, Fan Y, Shahzad M, Hayat K, Li H, Ihsan A, Muhammad KS, Usman M, Zhang S, Yuan L, Ullah S, Paiva-Santos AC, Xu J. Gut-Thyroid axis: How gut microbial dysbiosis associated with euthyroid thyroid cancer. J Cancer 2022; 13(6):2014-2028. doi:10.7150/jca.66816. Available from https://www.jcancer.org/v13p2014.htm

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Graphic abstract

Thyroid cancer in humans has a fast-growing prevalence, with the most common lethal endocrine malignancy for unknown reasons. The current study was aimed to perform qualitative and quantitative investigation and characterization of the gut bacterial composition of euthyroid thyroid cancer patients. The fecal samples were collected from sixteen euthyroid thyroid cancer patients and ten from healthy subjects. The PCR-DGGE was conducted by targetting the V3 region of 16S rRNA gene, as well as real-time PCR for Bacteroides vulgatus, E.coli Bifidobacterium, Clostridium leptum and Lactobacillus were carried. High-throughput sequencing of V3+V4 region of 16S rRNA gene was performed on Hiseq 2500 platform on 20 (10 healthy & 10 diseased subjects) randomly selected fecal samples. The richness indices and comparative diversity analysis showed significant gut microbial modification in euthyroid thyroid cancer than control. At phylum level, there was significant enrichment of Firmicutes, Verrucomicrobia, while a significant decrease in Bacteroidetes was detected in the experimental group. At family statistics, significant high levels of Ruminococcaceae and Verrucomicrobiaceae, while the significant lower abundance of Bacteroidaceae, Prevotellaceae, Porphyromonadaceae, and Alcaligenaceae was after observed. It also found that the significantly raised level of Escherichia-Shigella, Akkermansia [Eubacterium]_coprostanoligenes, Dorea, Subdoligranulum, and Ruminococcus_2 genera, while significantly lowered genera of the patient group were Prevotella_9, Bacteroides and Klebsiella. The species-level gut microbial composition showed a significantly raised level of Escherichia coli in euthyroid thyroid cancer. Thus, this study reveals that euthyroid thyroid cancer patients have significant gut microbial dysbiosis. Moreover, Statistics (P<0.05) of each gut microbial taxa were significantly changed in euthyroid thyroid cancer patients. Therefore, the current study may propose new approaches to understanding thyroid cancer patients' disease pathways, mechanisms, and treatment.

Keywords: Euthyroid thyroid cancer, DGGE, High-throughput sequencing, Characterization, Gut microbiota.