Abstract

The gut microbiota plays a pivotal role in influencing drug metabolism and efficacy through intricate interactions with host physiology. This article provides a comprehensive review of the mechanisms by which gut microbiota impact drug metabolism and therapeutic outcomes, highlighting the therapeutic implications of these interactions.The gut microbiota, comprising a diverse ecosystem of microorganisms residing in the gastrointestinal tract, interacts with ingested drugs through enzymatic biotransformation, altering their pharmacokinetic profiles. Microbial enzymes, such as cytochrome P450 enzymes and β-glucuronidases, metabolize drugs into active or inactive metabolites, thereby modulating drug bioavailability, efficacy, and toxicity. Moreover, microbial-mediated alterations in drug absorption, distribution, metabolism, and excretion processes contribute to inter-individual variability in drug responses. Beyond metabolism, gut microbiota-derived metabolites, including short-chain fatty acids and secondary bile acids, exert regulatory effects on host metabolic pathways and immune responses, influencing drug efficacy and therapeutic outcomes. Dysbiosis of the gut microbiota, characterized by shifts in microbial composition and function, can disrupt drug metabolism pathways, leading to altered drug responses and treatment failures.

Therapeutically, targeting the gut microbiota represents a promising strategy to optimize drug therapy. Approaches such as probiotics, prebiotics, antibiotics, and fecal microbiota transplantation (FMT) aim to modulate microbiota composition and enhance drug efficacy while minimizing adverse effects. Personalized medicine initiatives integrating gut microbiota profiling offer potential for tailored therapeutic regimens based on individual microbiome signatures.