Drug-microbiota interactions: an emerging priority for precision medicine.

Area of Science:

• Pharmacology
• Microbiology
• Genomics

Background:

• Individual variability in drug response (IVDR) leads to adverse drug reactions (ADRs) and treatment failures, imposing significant health and economic burdens.
• Pharmacogenomics, while informative, explains only a limited portion of IVDR, highlighting the need for alternative explanations.
• The gut microbiota, termed the 'second genome,' and its metabolites are increasingly recognized for their role in modulating therapeutic outcomes.

Purpose of the Study:

• To provide an up-to-date overview of pharmacomicrobiomics, exploring the interactions between gut microbiota and drugs used for systemic diseases.
• To summarize how gut microbiota influence drug absorption, distribution, metabolism, and excretion (ADME).
• To discuss the reciprocal effects of drugs on gut microbiota composition, function, and host immune responses.

Main Methods:

• Review of current literature on pharmacomicrobiomics and its impact on drug response.
• Analysis of studies investigating drug-microbiota interactions in various disease contexts (cancer, cardiovascular, endocrine).
• Discussion of multi-omics approaches and data integration strategies for translational research.

Main Results:

• Gut microbiota directly and indirectly affect drug ADME, influencing therapeutic efficacy and safety.
• Drugs can alter gut microbiota composition and function, leading to altered microbial metabolism and host immune responses.
• Interactions between drugs and gut microbiota are complex and disease-specific.

Conclusions:

• Pharmacomics offers a promising approach to address IVDR and enhance patient outcomes.
• Integrating multi-omics data (genomics, metagenomics) is crucial for understanding drug-microbiota interactions.
• Further research and clinical translation are imperative to realize the full potential of pharmacomicrobiomics in precision medicine.