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Review
. 2021 Dec 1;12(6):2172-2189.
doi: 10.1093/advances/nmab085.

Contribution of Biotransformations Carried Out by the Microbiota, Drug-Metabolizing Enzymes, and Transport Proteins to the Biological Activities of Phytochemicals Found in the Diet

Anna Boronat  1 , Jose Rodriguez-Morató  1   2   3 , Gabriele Serreli  4 , Montserrat Fitó  2   5 , Rachel F Tyndale  6   7 , Monica Deiana  4 , Rafael de la Torre  1   2   3
Affiliations
Review

Contribution of Biotransformations Carried Out by the Microbiota, Drug-Metabolizing Enzymes, and Transport Proteins to the Biological Activities of Phytochemicals Found in the Diet

Anna Boronat et al. Adv Nutr. .

Abstract

The consumption of dietary phytochemicals has been associated with several health benefits and relevant biological activities. It is postulated that biotransformations of these compounds regulated by the microbiota, Phase I/II reactions, transport proteins, and deconjugating enzymes contribute not only to their metabolic clearance but also, in some cases, to their bioactivation. A number of factors (age, genetics, sex, physiopathological conditions, and the interplay with other dietary phytochemicals) modulating metabolic activities are important sources and contributors to the interindividual variability observed in clinical studies evaluating the biological activities of phytochemicals. In this review, we discuss all the processes that can affect the bioaccessibility and beneficial effects of these bioactive compounds. Herein, we argue that the role of these factors must be further studied to correctly understand and predict the effects observed following the intake of phytochemicals. This is, in particular, with regard to in vitro investigations, which have shown great inconsistency with preclinical and clinical studies. The complexity of in vivo metabolic activity and biotransformation should therefore be considered in the interpretation of results in vitro and their translation to human physiopathology.

Keywords: drug-metabolizing enzymes; interindividual variability; microbiota; phenolic compounds; phytochemicals; phytochemicals metabolism; transport proteins.

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Figures

FIGURE 1
FIGURE 1
Schematic representation of major Phase II metabolic reactions and their biological consequences. COMT, catechol-O-methyltransferase; GSH, glutathione; NAT, N-acetyltransferase; SULT, sulfotransferases; UGT, uridine glucuronyl transferases.
FIGURE 2
FIGURE 2
The intra- and extracellular concentration of glucuronide and sulfate metabolites is regulated by transport proteins and by deconjugating enzymes. Expression, distribution, and activation of metabolizing enzymes and transporters are influenced by pathophysiological status (e.g., activation of macrophages) and by protein polymorphisms. ABC, ATP-binding cassette; ARS, arylsulfatases; β-gluc, β-glucuronidase; ER, endoplasmic reticulum; OATP, organic-anion-transporting polypeptides; OCT, organic cation transporter; SULT, sulfotransferase; STS, steroid sulfatase; UGT, UDP-glucuronosyltransferase.
FIGURE 3
FIGURE 3
Schematic representation of the interplay between phytochemicals and microbiota, drug-metabolizing enzymes, and transport proteins before reaching the target tissue, all being potential sources of inter-individual variability.
See this image and copyright information in PMC

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