Use of Physiologically Based Kinetic Modeling to Predict Rat Gut Microbial Metabolism of the Isoflavone Daidzein to S-Equol and Its Consequences for ERα Activation.

ABSTRACT:

Scope

To predict gut microbial metabolism of xenobiotics and the resulting plasma concentrations of metabolites formed, an in vitro-in silico-based testing strategy is developed using the isoflavone daidzein and its gut microbial metabolite S-equol as model compounds.

Methods and results

Anaerobic rat fecal incubations are optimized and performed to derive the apparent maximum velocities (V_max ) and Michaelis-Menten constants (K_m ) for gut microbial conversion of daidzein to dihydrodaidzein, S-equol, and O-desmethylangolensin, which are input as parameters for a physiologically based kinetic (PBK) model. The inclusion of gut microbiota in the PBK model allows prediction of S-equol concentrations and slightly reduced predicted maximal daidzein concentrat

SUBMITTER: Wang Q 

PROVIDER: S-EPMC7154660 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature