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Gut Microbiota Participates in Antithyroid Drug Induced Liver Injury Through the Lipopolysaccharide Related Signaling

Jiayu Sun1, Fuya Zhao1, Baiqiang Lin1

  • 1Department of Oncology and Laparoscopy Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China.

Frontiers in Pharmacology
|January 4, 2021
PubMed

Insights

Antithyroid drugs alter gut microbiota structure, potentially causing liver injury through increased endotoxemia. This study links drug-induced gut changes to liver damage via lipopolysaccharide.

Area of Science:

  • Microbiology
  • Pharmacology
  • Hepatology

Background:

  • Gut microbiota dysbiosis is linked to drug side effects via the intestinal endotoxemia hypothesis.
  • The relationship between antithyroid drugs (methimazole, propylthiouracil), gut microbiota, and drug-induced liver injury remains unclear.

Purpose of the Study:

  • To investigate if antithyroid drugs induce gut microbiota dysbiosis.
  • To determine the correlation between gut microbiota alterations and antithyroid drug-induced liver injury.

Main Methods:

  • Human clinical trials with Graves' disease patients (methimazole/propylthiouracil groups) and healthy controls.
  • Animal studies using Sprague-Dawley rats with varying doses of methimazole and propylthiouracil.
  • Analysis of gut microbiota structure/function, clinical parameters, liver function indexes, and intestinal barrier integrity.

Main Results:

  • Antithyroid drugs significantly altered gut microbiota structure in both human and animal studies.
  • Increased liver function indexes correlated with gut microbiota changes.
  • Elevated lipopolysaccharide levels and a compromised intestinal barrier were observed following antithyroid drug administration.

Conclusions:

  • Antithyroid drugs alter gut microbiota structure.
  • Gut microbiota dysbiosis may contribute to antithyroid drug-induced liver injury, potentially mediated by the intestinal endotoxemia pathway.
Keywords:
antithyroid drugsgut microbiotaintestinal barrierlipopolysaccharideliver injury

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