Complex relationship between gut microbiota and thyroid dysfunction: a bidirectional two-sample Mendelian randomization study

Front Endocrinol (Lausanne). 2023 Nov 10:14:1267383. doi: 10.3389/fendo.2023.1267383. eCollection 2023.

Abstract

Background: Many studies have reported the link between gut microbiota and thyroid dysfunction. However, the causal effect of gut microbiota on thyroid dysfunction and the changes in gut microbiota after the onset of thyroid dysfunction are not clear.

Methods: A two-sample Mendelian randomization (MR) study was used to explore the complex relationship between gut microbiota and thyroid dysfunction. Data on 211 bacterial taxa were obtained from the MiBioGen consortium, and data on thyroid dysfunction, including hypothyroidism, thyroid-stimulating hormone alteration, thyroxine deficiency, and thyroid peroxidase antibodies positivity, were derived from several databases. Inverse variance weighting (IVW), weighted median, MR-Egger, weighted mode, and simple mode were applied to assess the causal effects of gut microbiota on thyroid dysfunction. Comprehensive sensitivity analyses were followed to validate the robustness of the results. Finally, a reverse MR study was conducted to explore the alteration of gut microbiota after hypothyroidism onset.

Results: Our bidirectional two-sample MR study revealed that the genera Intestinimonas, Eubacterium brachy group, Ruminiclostridium5, and Ruminococcaceae UCG004 were the risk factors for decreased thyroid function, whereas the genera Bifidobacterium and Lachnospiraceae UCG008 and phyla Actinobacteria and Verrucomicrobia were protective. The abundance of eight bacterial taxa varied after the onset of hypothyroidism. Sensitivity analysis showed that no heterogeneity or pleiotropy existed in the results of this study.

Conclusion: This novel MR study systematically demonstrated the complex relationship between gut microbiota and thyroid dysfunction, which supports the selection of more targeted probiotics to maintain thyroid-gut axis homeostasis and thus to prevent, control, and reverse the development of thyroid dysfunction.

Keywords: Mendelian randomization; gut microbiota; hypothyroidism; thyroid dysfunction; thyroid-gut axis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Clostridiales
  • Gastrointestinal Microbiome*
  • Humans
  • Hypothyroidism* / genetics
  • Mendelian Randomization Analysis
  • Thyroxine

Substances

  • Thyroxine

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. The work was supported by the Natural Science Foundation of Shandong Province (grant number ZR2021QH047) and the Clinical Science and Technology Innovation Development Program of Jinan (grant number 202134036).