Pharmaceutical and Biomedical Research

en Pharmacomicrobiomics: genetic variations in the human gut microbiome and their influence on drug metabolism and efficacy فارماکولوژی Pharmacology مروری Review article Background: The human gut microbiome, a vast and genetically diverse ecosystem encoding millions of genes, significantly contributes to individual differences in how drugs are metabolized, their effectiveness, and potential toxicity. This interaction forms the foundation of pharmacomicrobiomics, an emerging field that positions the microbiome as a crucial element in precision medicine, extending beyond traditional pharmacogenomics focused solely on the human genome. Objectives: This review aims to synthesize the bidirectional dynamics between the gut microbiome and pharmaceuticals, highlighting how microbial genetic variations influence drug responses, while also exploring strategies to leverage these insights for improved personalized therapies. Methods: We conducted a comprehensive literature review, integrating findings from metagenomic studies, clinical case reports, and experimental models, drawing on multi-omics data to examine direct and indirect microbial effects on drug metabolism across various therapeutic areas. Results: Key findings reveal that strain-specific microbial enzymes, such as reductases, hydrolases, and β-glucuronidases, directly biotransform drugs like digoxin (leading to inactivation), irinotecan (causing reactivation and GI toxicity), and levodopa (reducing efficacy in Parkinson's disease). Indirect influences occur through microbial metabolites, including short-chain fatty acids and secondary bile acids, which modulate host enzymes, transporters, and immune pathways, as seen in enhanced immunotherapy responses in oncology. Genetic factors like strain-level polymorphisms, horizontal gene transfer, and population-specific variations drive this diversity, with drugs reciprocally altering microbiome composition to create feedback loops affecting long-term efficacy. Conclusion: Despite challenges in standardizing multi-omics integration and clinical translation, advancements in machine learning, enzyme inhibitors, engineered probiotics, and fecal microbiota transplantation hold promise for microbiome-targeted pharmacotherapy. By incorporating the microbial metagenome alongside the human genome, pharmacomicrobiomics can uncover overlooked factors in drug variability, reduce adverse effects, optimize dosing, and advance truly individualized medicine.   beta-Glucuronidase, Biotransformation, Fecal Microbiota Transplantation, Immunomodulation, Bile Acids and Salts 0 0 http://pbr.mazums.ac.ir/browse.php?a_code=A-10-1467-1&slc_lang=en&sid=1 Ifeoma Nwamaka Monago championsteve01@gmail.com 100319475328460012386 100319475328460012386 Yes Faculty of Medicine, College of Health Sciences, Nnamdi Azikiwe University, Awka, Nigeria Tobechi Brendan Nnanna tnnanna49@gmail.com 100319475328460012387 100319475328460012387 No College of Life and Health Sciences, Aston University, Birmingham, UK Ikemefuna Nnamdi Onyeyili onyeyiliikemefuna@gmail.com 100319475328460012388 100319475328460012388 No Ahmadu Bello University (ABU), Zaria, Nigeria Prince Mishael Mankwe mishaelclarkson@gmail.com 100319475328460012389 100319475328460012389 No University of Port-Harcourt, Port-Harcourt, Nigeria Chibuike Stephen Nzereogu chibuikenzereogu1@gmail.com 100319475328460012390 100319475328460012390 No Faculty of Pharmaceutical Sciences, University of Port-harcourt, Port-harcourt, Nigeria Okechukwu Damian Obi Alhajiobi99@gmail.com 100319475328460012391 100319475328460012391 No Bedfordshire University, Luton, UK Chinedu Nnaemeka Ilokanuno cn.ilokanuno@unizik.edu.ng 100319475328460012392 100319475328460012392 No Nnamdi Azikiwe University, Awka, Nigeria Ezinwanne Oluchi Udeogalanya udeogalanyaezinwanne@gmail.com 100319475328460012393 100319475328460012393 No University of Port-Harcourt, Port-Harcourt, Nigeria