Use of Physiologically Based Pharmacokinetic Modeling to Predict Human Gut Microbial Conversion of Daidzein to S-Equol

Qianrui Wang*, Bert Spenkelink, Rungnapa Boonpawa, Ivonne M.C.M. Rietjens

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

16 Citations (Scopus)

Abstract

A physiologically based pharmacokinetic (PBPK) model was developed for daidzein and its metabolite S-equol. Anaerobic in vitro incubations of pooled fecal samples from S-equol producers and nonproducers allowed definition of the kinetic constants. PBPK model-based predictions for the maximum daidzein plasma concentration (Cmax) were comparable to literature data. The predictions also revealed that the Cmax of S-equol in producers was only up to 0.22% that of daidzein, indicating that despite its higher estrogenicity, S-equol is likely to contribute to the overall estrogenicity upon human daidzein exposure to a only limited extent. An interspecies comparison between humans and rats revealed that the catalytic efficiency for S-equol formation in rats was 210-fold higher than that of human S-equol producers. The described in vitro-in silico strategy provides a proof-of-principle on how to include microbial metabolism in humans in PBPK modeling as part of the development of new approach methodologies (NAMs).

Original languageEnglish
Pages (from-to)343-352
JournalJournal of Agricultural and Food Chemistry
Volume70
Issue number1
Early online date2 Dec 2021
DOIs
Publication statusPublished - 2022

Keywords

  • daidzein
  • gut microbiota
  • physiologically based pharmacokinetic (PBPK) modeling
  • S-equol

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