Microbiome Is a Functional Modifier of P450 Drug Metabolism

  • Joseph L. Dempsey
  • Julia Yue CuiEmail author
Microbiome (A Patterson, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Microbiome


Host cytochrome P450s (P450s) play important roles in the bioactivation and detoxification of numerous therapeutic drugs, environmental toxicants, dietary factors, as well as endogenous compounds. Gut microbiome is increasingly recognized as our “second genome” that contributes to the xenobiotic biotransformation of the host, and the first-pass metabolism of many orally exposed chemicals is a joint effort between host drug-metabolizing enzymes including P450s and gut microbiome. Gut microbiome contributes to the drug metabolism via two distinct mechanisms: direct mechanism refers to the metabolism of drugs by microbial enzymes, among which reduction and hydrolysis (or deconjugation) are among the most important reactions, whereas indirect mechanism refers to the influence of host receptors and signaling pathways by microbial metabolites. Many types of microbial metabolites, such as secondary bile acids (BAs), short-chain fatty acids (SCFAs), and tryptophan metabolites, are known regulators of human diseases through modulating host xenobiotic-sensing receptors. To study the roles of gut microbiome in regulating host drug metabolism including P450s, several models including germ-free mice, antibiotics, or probiotics treatments, have been widely used. The present review summarized the current information regarding the interactions between the gut microbiome and the host P450s in xenobiotic biotransformation organs such as liver, intestine, and kidney, highlighting the remote sensing mechanisms underlying gut microbiome-mediated regulation of host xenobiotic biotransformation. In addition, the roles of bacterial, fungal, and other microbiome kingdom P450s, which is an understudied area of research in pharmacology and toxicology, are discussed.


Gut microbiome Cytochrome P450s Xenobiotic metabolism Drug metabolism Personalized medicine Gut-liver axis 


Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of Environmental and Occupational Health SciencesUniversity of WashingtonSeattleUSA

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