Perioperative gut microbiota homeostasis and its interactions with anesthetic agents: recent advances

The perioperative period is a critical and acute phase during which host-microbiota interactions play an essential role in determining susceptibility to anesthetic exposure and post-surgical stress. Immune homeostasis, gut barrier integrity, and metabolic regulation, as well as gut-brain and gut-liver axis, are highly dependent on the gut microbiota. However, this microbial ecosystem is disrupted during the perioperative period due to the combined effects of fasting, bowel preparation, surgical stress, hemodynamic alterations, and antibiotic and opioid use. Growing evidence has linked perioperative dysbiosis to a wide range of adverse outcomes, including infectious complications, anastomotic leakage, postoperative ileus, organ dysfunction, and perioperative neurocognitive disorders. Meanwhile, anesthetic and analgesic agents do not act in isolation from this ecosystem; rather, they engage in a bidirectional chemical interaction with the microbiota. These interactions can alter microbial structure and metabolite profiles, thereby influencing host metabolic processes, while microbial activity, in turn, affects drug disposition, immune response, and neuroinflammation. In this review, we first describe the vulnerability of gut microbiota homeostasis during the perioperative period and its associated clinical consequences. We subsequently elaborate on the mechanistic framework of anesthetic-microbiota crosstalk, highlighting pathways involving vascular, epithelial, immune and neural signaling. Then, we summarize emerging evidence demonstrating that different anesthetic and analgesic regimens generate discrete microbiota-metabolite signatures, which may underlie intersubject differences in postoperative recovery trajectories. Finally, we describe perioperative microbiota-targeted strategies, including probiotics and synbiotics, postbiotics and microbial consortia, nutritional optimization, and microbiome-based customization of anesthetic and analgesic protocols. Collectively, existing data suggest that preserving and actively modulating gut microbiota homeostasis represents a promising yet underexplored strategy for improving the safety of anesthesia and postoperative outcomes.