Microbes and medicines: interrelationships between pharmaceuticals and the gut microbiome

The human gut microbiome plays a critical role in modulating pharmacological and toxicological responses to medications. With a gene pool vastly exceeding that of the human host, the gut microbiome acts as a metabolically active organ capable of transforming, inactivating, or accumulating drugs. This review explores the bidirectional interplay between prescription medicines and the gut microbiome, encompassing three key mechanisms: direct biotransformation by microbial enzymes, indirect modu-lation of host metabolism and signaling pathways, and drug bioaccumulation within microbial cells. Particular attention is given to six major drug classes: immunothera-peutics, chemotherapeutics, antidepressants, statins, hypoglycemics, and antihyperten-sives. The ways in which individual microbial profiles can influence therapeutic outcomes are also reviewed. We examined how common non-antibiotic pharmaceu-ticals can significantly alter microbial diversity and promote antimicrobial resistance. Strategies to enhance drug efficacy through microbiome modulation, including pro-biotics, prebiotics, and fecal microbiota transplantation (FMT), are critically assessed. Experimental models ranging from in vitro batch and chemostat systems to animal and clinical studies are compared in terms of their utility for studying drug‒microbiome interactions. Finally, emerging evidence suggesting the gut microbiota composition may serve as a predictive biomarker for personalized medicine and therapeutic success is highlighted. Understanding and harnessing the complex interrelationships between medicines and microorganisms could offer novel avenues to optimize treatment out-comes and mitigate adverse drug effects.