Pharmacomicrobiomics in Hepatobiliary Disease: The Role of the Gut Microbiota in Drug Disposition and Safety
DOI:
https://doi.org/10.64784/077Palabras clave:
gut microbiota, drug metabolism, hepatobiliary disease, gut–liver axis, bile acids, pharmacokinetics, drug toxicity, enterohepatic circulation, precision medicineResumen
The gut microbiota has emerged as a key modulator of drug metabolism, efficacy, and toxicity, adding a critical layer of complexity to pharmacological processes traditionally attributed solely to host physiology. In hepatobiliary disease, this interaction acquires particular relevance due to alterations in bile acid metabolism, intestinal barrier function, immune regulation, and enterohepatic circulation. This review synthesizes current evidence on microbiota–drug interactions within hepatobiliary contexts, integrating mechanistic, translational, and clinical data to provide a coherent pharmacological framework. The analyzed literature consistently demonstrates that intestinal microorganisms can directly biotransform xenobiotics, modify effective bioavailability, and generate metabolites with altered pharmacodynamic or toxicological properties. In parallel, microbial modulation of bile acid pools and signaling pathways indirectly influences hepatic drug-metabolizing enzymes, transporters, and inflammatory responses. The reciprocal capacity of drugs to reshape microbial composition further contributes to dynamic and time-dependent variability in drug exposure. Collectively, these mechanisms help explain interindividual differences in therapeutic response and susceptibility to adverse drug reactions that are frequently observed in hepatobiliary disease but remain insufficiently accounted for by conventional dosing paradigms. By consolidating these findings, this review highlights the gut microbiota as an integral component of hepatobiliary pharmacology and underscores its relevance for advancing more precise, individualized, and safer therapeutic strategies.
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