Influence of Gut Microbiota Alterations on Drug Metabolism BeTherapeutic Efficacy: A Systematic Review

The human gut microbiota, a diverse ecosystem of microorganisms, has become a focal point in pharmacologicalresearch due to its influence on drug metabolism and therapeutic efficacy. This systematic review synthesizesfindings from 150 clinical and preclinical studies to understand how alterations in gut microbiota impact drugmetabolism and clinical outcomes. A meta-analysis revealed significant microbiota-dependent variability in drugmetabolism, with a pooled standardized mean difference (SMD) of 0.45 (95% CI: 0.30–0.60, p < 0.001).Chemotherapeutic agents, such as irinotecan, exhibited the most significant effects, with microbial enzymes, likeβ-glucuronidases, playing a critical role in the reactivation of toxic drug metabolites. Additionally, gut microbiotainfluences the bioavailability of other drugs, such as digoxin, which is inactivated by Eggerthella lenta. Thereview also highlights the potential of microbiota-modulating interventions, such as probiotics and fecalmicrobiota transplantation (FMT), to optimize therapeutic outcomes. These findings emphasize the need formicrobiota profiling in personalized medicine and the development of standardized microbiota-modulatingtherapies for better drug efficacy and reduced toxicity.