Microbiome-drug interactions: implications for pharmacokinetics, drugefficacy, and safety

Abstract

The human microbiome has emerged as a crucial modulator of drug response, significantlyinfluencing pharmacokinetics, efficacy, and safety. This review explores the multifacetedinteractions between the gut microbiota and pharmaceuticals, highlighting the bidirectional natureof these relationships. A literature search covering publications from 2010 to 2025 was conductedusing databases such as Google Scholar, PubMed, Web of Science, Embase, and Scopus. Keywordsincluded “Microbiota”, “Pharmacokinetics”, “Drug Metabolism”, “Drug Interactions”,“Gastrointestinal Microbiome”and “Precision Medicine.” Microbial enzymes can metabolize drugsbefore absorption, alter their chemical structures, and influence their bioavailability and systemicexposure. These microbiome-mediated transformations can enhance or diminish drug efficacy, leadto the formation of toxic metabolites, or interfere with drug activation, particularly in prodrugs.Conversely, drugs can perturb microbial composition and diversity, potentially contributing todysbiosis and long-term health consequences. Variability in individual microbiota profiles isincreasingly recognized as a contributor to inter-individual differences in drug responses, offeringan explanation for observed inconsistencies in therapeutic outcomes and adverse drug reactions.Notable examples include the microbial inactivation of digoxin. In recent years, the humanmicrobiome has emerged as a crucial determinant of health and disease, influencing a wide array ofphysiological processes including digestion, immunity, and neurochemical signaling. Among itslesser-known but increasingly recognized roles is its profound impact on drug metabolism andtherapeutic outcomes. These microbiome–drug interactions are now understood to contributesignificantly to the variability in drug response observed among individuals, challenging thetraditional one-size-fits-all approach to pharmacotherapy.