Publication:

The role of gut microbiota in drug metabolism: implications for personalized medicine: a systematic review

Interindividual variability in drug response remains a significant challenge in clinical pharmacology. Emerging evidence suggests that the gut microbiota contributes to variability in drug metabolism, efficacy, and toxicity. A systematic search of PubMed, Scopus, Nature Portfolio, and relevant pharmacology journals was conducted for studies published between January 2019 and August 2025 using predefined keywords related to pharmacomicrobiomics and drug-microbiota interactions. Peer-reviewed human and animal studies evaluating mechanistic or clinical implications were included. Study selection and reporting followed PRISMA 2020 guidelines. Risk of bias was assessed using the Cochrane RoB 2 tool for randomized trials, the Newcastle-Ottawa Scale for observational studies, and SYRCLE’s tool for animal studies. Data were synthesized qualitatively due to methodological heterogeneity. Of 2,847 identified records, 158 studies met inclusion criteria. Clinically significant microbiota-drug interactions were observed across multiple drug classes including cardiac glycosides, anti-inflammatory agents, chemotherapeutics, antidepressants, immunosuppressants, and immunotherapies. Mechanisms included direct microbial biotransformation, metabolite reactivation, modulation of host metabolic pathways, and immune-mediated effects. These interactions were associated with altered pharmacokinetics and variable therapeutic outcomes. The gut microbiota is an important determinant of drug response variability. Incorporating microbiome-based insights into pharmacotherapy may enhance individualized treatment strategies. Further well-designed clinical studies are needed to support routine clinical implementation.