PBK Model-Based Prediction of Intestinal Microbial and Host Metabolism of Zearalenone and Consequences for its Estrogenicity

Diana M. Mendez-Catala*, Qianrui Wang*, Ivonne M.C.M. Rietjens

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

10 Citations (Scopus)

Abstract

Scope: The aim of the present study is to develop physiologically-based kinetic (PBK) models for rat and human that include intestinal microbial and hepatic metabolism of zearalenone (ZEN) in order to predict systemic concentrations of ZEN and to obtain insight in the contribution of metabolism by the intestinal microbiota to the overall metabolism of ZEN. Methods and Results: In vitro derived kinetic parameters, apparent maximum velocities (Vmax) and Michaelis–Menten constants (Km) for liver and intestinal microbial metabolism of ZEN are included in the PBK models. The models include a sub-model for the metabolite, α-zearalenol (α-ZEL), a metabolite known to be 60-times more potent as an estrogen than ZEN. Integrating intestinal microbial ZEN metabolism into the PBK models revealed that hepatic metabolism drives the formation of α-ZEL. Furthermore, the models predicted that at the tolerable daily intake (TDI) of 0.25 µg kg−1 bw the internal concentration of ZEN and α-ZEL are three-orders of magnitude below concentrations reported to induce estrogenicity in vitro. Conclusion: It is concluded that combining kinetic data on liver and intestinal microbial metabolism in a PBK model facilitates a holistic view on the role of the intestinal microbiota in the overall metabolism of the foodborne xenobiotic ZEN and its bioactivation to α-ZEL.

Original languageEnglish
Article number2100443
JournalMolecular Nutrition and Food Research
Volume65
Issue number23
Early online date2021
DOIs
Publication statusPublished - 2021

Keywords

  • blood concentration
  • hepatic metabolism
  • intestinal microbiota
  • PBK
  • urine excretion
  • zearalenone
  • α-zearalenol

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