Microbiota–drug interactions: Impact on metabolism and efficacy of therapeutics

Ellen M. Wilkinson, Zehra Esra Ilhan, Melissa M. Herbst-Kralovetz

Research output: Contribution to journalReview articlepeer-review

69 Scopus citations

Abstract

The microbiome not only represents a vital modifier of health and disease, but is a clinically important drug target. Therefore, study of the impact of the human microbiome on drug metabolism, toxicity and efficacy is urgently needed. This review focuses on gut and vaginal microbiomes, and the effect of those microbiomes or components thereof on the pharmacokinetics of specific chemotherapeutic agents, immunotherapies, anti-inflammatory and antimicrobial drugs. In some cases, the presence of specific bacterial species within the microbiome can alter the metabolism of certain drugs, such as chemotherapeutic agents and antiviral drugs. These microbiota–drug interactions are identified mostly through studies using germ-free or microbiome-depleted animal models, or by the administration of specific bacterial isolates. The biotransformation of drugs can cause drug-related toxicities; however, biotransformation also provides a mechanism by which drug developers could exploit host microbiota to create more site-specific drugs. Within this review we consider the importance of the route of drug administration and interactions with microbiota at various mucosal sites. Notably, we discuss the potential utility of bacterial therapeutics in altering the microbiome to enhance therapeutic efficacy and clinical outcomes in a personalized fashion. Based on the data to date, there is a clinically important relationship between microbiota and drug metabolism throughout the lifespan; therefore, profiling of the human microbiome will be essential in order to understand the mechanisms by which these microbiota–drug interactions occur and the degree to which this complex interplay affects drug efficacy.

Original languageEnglish (US)
Pages (from-to)53-63
Number of pages11
JournalMaturitas
Volume112
DOIs
StatePublished - Jun 2018

Keywords

  • Biotransformation
  • Drug metabolism
  • Efficacy
  • Microbiome
  • Precision medicine
  • Therapeutics

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology
  • Obstetrics and Gynecology

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