Mendelian randomization suggests a causal relationship between gut dysbiosis and thyroid cancer

Feng Zhu; Pengpeng Zhang; Ying Liu; Chongchan Bao; Dong Qian; Chaoqun Ma; Hua Li; Ting Yu

doi:10.3389/fcimb.2023.1298443

Mendelian randomization suggests a causal relationship between gut dysbiosis and thyroid cancer

Front Cell Infect Microbiol. 2023 Dec 1:13:1298443. doi: 10.3389/fcimb.2023.1298443. eCollection 2023.

Authors

Feng Zhu^#^{1

2}, Pengpeng Zhang^#^{3

4}, Ying Liu^#⁵, Chongchan Bao^#⁶, Dong Qian⁵, Chaoqun Ma⁵, Hua Li⁷, Ting Yu¹

Affiliations

¹ Department of Gastroenterology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China.
² Department of Gastroenterology, The First People's Hospital of Kunshan, Suzhou, China.
³ Department of Lung Cancer Surgery, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.
⁴ Department of Thoracic Surgery, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China.
⁵ Department of General Surgery, Affiliated Hospital of Nanjing University of TCM, Jiangsu Province Hospital of TCM, Nanjing, China.
⁶ Department of Breast and Thyroid Surgery, The Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, China.
⁷ Department of General Surgery, The Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, China.

^# Contributed equally.

Abstract

Background: Alterations in gut microbiota composition and function have been linked to the development and progression of thyroid cancer (TC). However, the exact nature of the causal relationship between them remains uncertain.

Methods: A bidirectional two-sample Mendelian randomization (TSMR) analysis was conducted to assess the causal connection between gut microbiota (18,340 individuals) and TC (6,699 cases combined with 1,613,655 controls) using data from a genome-wide association study (GWAS). The primary analysis used the inverse-variance weighted (IVW) method to estimate the causal effect, with supplementary approaches including the weighted median, weighted mode, simple mode, and MR-Egger. Heterogeneity and pleiotropy were assessed using the Cochrane Q test, MR-Egger intercept test, and MR-PRESSO global test. A reverse TSMR analysis was performed to explore reverse causality.

Results: This study identified seven microbial taxa with significant associations with TC. Specifically, the genus Butyrivibrio (OR: 1.127, 95% CI: 1.008-1.260, p = 0.036), Fusicatenibacter (OR: 1.313, 95% CI: 1.066-1.618, p = 0.011), Oscillospira (OR: 1.240, 95% CI: 1.001-1.536, p = 0.049), Ruminococcus2 (OR: 1.408, 95% CI: 1.158-1.711, p < 0.001), Terrisporobacter (OR: 1.241, 95% CI: 1.018-1.513, p = 0.032) were identified as risk factors for TC, while The genus Olsenella (OR: 0.882, 95% CI: 0.787-0.989, p = 0.031) and Ruminococcaceae UCG004 (OR: 0.719, 95% CI: 0.566-0.914, p = 0.007) were associated with reduced TC risk. The reverse MR analysis found no evidence of reverse causality and suggested that TC may lead to increased levels of the genus Holdemanella (β: 0.053, 95% CI: 0.012~0.094, p = 0.011) and decreased levels of the order Bacillales (β: -0.075, 95% CI: -0.143~-0.006, p = 0.033). No significant bias, heterogeneity, or pleiotropy was detected in this study.

Conclusion: This study suggests a potential causal relationship between gut microbiota and TC, providing new insights into the role of gut microbiota in TC. Further research is needed to explore the underlying biological mechanisms.

Keywords: Mendelian randomization; bidirectional; causal relationship; gut dysbiosis; thyroid cancer.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Causality
Clostridiales
Dysbiosis*
Genome-Wide Association Study
Humans
Mendelian Randomization Analysis
Thyroid Neoplasms* / genetics

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the National Natural Science Foundation of China [grant number: 82000508, TY, PI].