Drug pharmacomicrobiomics and toxicomicrobiomics: from scattered reports to systematic studies of drug–microbiome interactions

ABSTRACT

Introduction: Pharmacomicrobiomics and toxicomicrobiomics study how variations within the human microbiome (the combination of human-associated microbial communities and their genomes) affect drug disposition, action, and toxicity. These emerging fields, interconnecting microbiology, bioinformatics, systems pharmacology, and toxicology, complement pharmacogenomics and toxicogenomics, expanding the scope of precision medicine.

Areas covered: This article reviews some of the most recently reported pharmacomicrobiomic and toxicomicrobiomic interactions. Examples include the impact of the human gut microbiota on cardiovascular drugs, natural products, and chemotherapeutic agents, including immune checkpoint inhibitors. Although the gut microbiota has been the most extensively studied, some key drug-microbiome interactions involve vaginal, intratumoral, and environmental bacteria, and are briefly discussed here. Additionally, computational resources, moving the field from cataloging to predicting interactions, are introduced.

Expert opinion: The rapid pace of discovery triggered by the Human Microbiome Project is moving pharmacomicrobiomic research from scattered observations to systematic studies focusing on screening microbiome variants against different drug classes. Better representation of all human populations will improve such studies by avoiding sampling bias, and the integration of multiomic studies with designed experiments will allow establishing causation. In the near future, pharmacomicrobiomic testing is expected to be a key step in screening novel drugs and designing precision therapeutics.

KEYWORDS:

• Bioinformatics
• genomics
• normal flora
• metabolomics
• metabonomics
• microbiota
• microbiome
• systems biology
• systems pharmacology
• toxicology

Article Highlights

• Pharmacomicrobiomics describes the effect of microbiome variations on drug fate and action.

• Toxicomicrobiomics can be defined as the effect of microbiome variations on xenobiotics, poisons, and drug adverse effects.

• The human gut microbiota differentially affects the bioavailability and efficacy of dozens of drugs. Classical examples include digoxin metabolism and acetaminophen toxicity.

• Some more complex interactions involve an interplay between the gut microbiota, immune system, and administered drugs, such as the case of cyclophosphamide and immune checkpoint inhibitors.

• In addition to cardiovascular and anticancer drugs, plant xenobiotics and other dietary supplements are among the chemicals that are mostly affected by the gut microbiota, which has long adapted to these dietary components.

• Other than the gut microbiota, vaginal bacteria may inactivate the antiviral agent tenofovir, and intratumoral bacteria were shown to inactivate the anticancer agent, gemcitabine.

• In the future, better-designed, more inclusive microbiome-wide studies will improve the predictive value of microbiome types, and pharmacomicrobiomic testing is expected to improve precision therapeutics.

This box summarizes key points contained in the article.

Author contributions

RKA conceived and outlined the article, assembled different contributions, and wrote the article in its final format; SHM, RY, MRR, and MTE reviewed literature, drafted different sections of the article, and reviewed and approved the manuscript in its final format.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

RKA is funded by Cairo University (Grant 2016-57), but no specific funding was provided for this review article.