Gut microbiota trigger host liver immune responses that affect drug-metabolising enzymes

Front Immunol. 2024 Dec 11:15:1511229. doi: 10.3389/fimmu.2024.1511229. eCollection 2024.

Abstract

There is increasing evidence that the intestinal microbiota plays an integral role in disease pathogenesis and treatment. Specifically, the intestinal microbiota significantly influences the pharmacokinetics and pharmacodynamics of orally administered drugs through direct involvement in drug metabolism and, consequently, drug bioavailability. However, the gut microbiota also exerts immunoregulatory effects on the liver-the organ primarily responsible for drug metabolism-thereby indirectly impacting the body's capacity to metabolise and process drugs. Individual differences in this pathway substantially contribute to the variability in clinical drug treatment outcomes observed between patients. This review examines the impact of liver immune responses, as triggered by the intestinal microbiota, on the activity of drug-metabolising enzymes and discusses the implications for precision medicine.

Keywords: drug-metabolising enzymes; epigenetic regulation; gut microbiota; liver immune response; precision medicine.

Publication types

  • Review

MeSH terms

  • Animals
  • Gastrointestinal Microbiome* / immunology
  • Humans
  • Inactivation, Metabolic
  • Liver* / immunology
  • Liver* / metabolism
  • Pharmaceutical Preparations / metabolism
  • Precision Medicine

Substances

  • Pharmaceutical Preparations

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This work was supported by the Discipline construction project of Guangdong Medical University (4SG22009G and 4SG23282G), the Funds for PHD researchers of Guangdong Medical University in 2021 (GDMUB2021021), and the Science and Technology Special Fund project of Guangdong Province in 2021 (2021A05199), the Guangdong Provincial Natural Science Foundation General Project (2022A1515012542), the Guangdong Basic and Applied Basic Research Foundation (No. 2023A1515111116), the Shenzhen Foundation of Science and Technology (No. JCYJ20230807151308018), the Zhanjiang Science and Technology Project (2023B01176), Shenzhen Longhua District Science and Technology Innovation Fund Projects (Nos. 2022045, 2022051, 2022056, 2022095, 2022123, 2021105, 2021115 and 2020036) and the Research Foundation of Shenzhen Longhua District Central Hospital (No. 202203).