How gut microbiota modulate anesthetic drug response and perioperative outcomes

The pursuit of precision in anesthesiology is persistently challenged by profound and unpredictable inter-patient variability in drug response. While pharmacogenomics has provided critical insights, a significant portion of this variability remains unexplained. Emerging evidence now positions the gut microbiota as a central, dynamic regulator of perioperative pharmacology. This review introduces and explores the concept, used here as a working label, of the anesthetic pharmacomicrobiome, defined as the set of microbial-host interactions that may influence perioperative drug disposition and effect. We adopt this descriptive shorthand for clarity. We synthesize evidence demonstrating how gut microbes clearly directly metabolize some perioperative drugs (for example opioids), and how other agents (for example propofol) have biologically plausible microbe-related interactions (propofol glucuronidation and potential microbial β-glucuronidase-mediated reactivation) that remain to be demonstrated in direct clinical studies; hypothesis-driven statements are labeled as 'Hypothesis/Speculative'. Furthermore, we detail how the perioperative period itself, through fasting, antibiotics, opioids, and surgical stress, assaults this microbial ecosystem, creating a vicious cycle of dysbiosis that amplifies risk for adverse outcomes like prolonged sedation, postoperative delirium, and chronic pain. Finally, we outline a translational roadmap, advocating for microbiome-based diagnostics, targeted therapeutic interventions, and integrated dosing models to usher in a new era of precision, microbiome-informed perioperative care.