In a groundbreaking study published in Translational Psychiatry, researchers have revealed that esketamine, a derivative of ketamine, can prevent postoperative sleep disturbances in patients who suffer from preoperative sleep disorders. The study uncovers an intriguing connection between esketamine’s therapeutic effects and the modulation of oral microbiota, opening new avenues for understanding the complex interplay between pharmacology, sleep regulation, and the microbiome.
Postoperative sleep disturbances are a common problem faced by many patients following surgery. Such disturbances often exacerbate recovery times, increase the risk of complications, and negatively impact the overall quality of life. While sleep disruptions are well-recognized in medical literature, effective interventions have remained elusive, particularly for patients with preexisting sleep disorders. This study addresses a critical gap by targeting a novel therapeutic pathway.
Esketamine, known primarily for its rapid antidepressant effects, is here explored for its potential in improving sleep outcomes post-surgery. The drug’s unique pharmacological profile, affecting glutamate neurotransmission via NMDA receptor antagonism, has previously been shown to influence mood and cognition. However, its impact on sleep regulation and its interaction with the oral microbiome had not been fully elucidated until this investigation.
The research team conducted a carefully designed clinical trial involving patients with documented preoperative sleep disorders scheduled for surgery. Patients were administered esketamine preoperatively, and their postoperative sleep architecture was monitored using polysomnography, alongside subjective sleep quality assessments. Remarkably, the esketamine group demonstrated significant improvements in both sleep duration and quality compared to control groups, underscoring the drug’s potential as a prophylactic agent against sleep disturbances after surgery.
Beyond its direct neuropharmacological effects, the study highlights the role of oral microbiota in mediating esketamine’s beneficial impact. Oral microbial communities are increasingly recognized as influential in systemic health, including neurological and sleep-related functions. Sequencing analyses revealed that esketamine administration altered the composition and diversity of oral microbiota, suggesting a possible mechanistic link.
The investigators propose that esketamine’s modulation of the oral microbiome could influence systemic inflammatory responses and neurochemical signaling, which are known contributors to sleep regulation. This hypothesis is supported by observed decreases in pro-inflammatory microbial taxa and increases in beneficial bacteria associated with anti-inflammatory effects. Such microbial shifts may facilitate a more conducive internal environment for restorative sleep.
This research not only expands our understanding of esketamine’s pharmacodynamics but also pioneers a novel concept in sleep medicine—pharmacologically targeting the microbiome to enhance sleep outcomes. The implications are vast, suggesting potential for microbiome-centered adjunct therapies aimed at improving postoperative recovery and managing sleep disorders more broadly.
Further mechanistic studies are warranted to elucidate the precise pathways by which oral microbiota influence central nervous system function and sleep. The study raises important questions about the bidirectional communication between the microbiome and brain, emphasizing the emerging field of neuro-microbiomics. Understanding these pathways could revolutionize approaches to neurological and psychiatric conditions that are intertwined with sleep disturbances.
Moreover, the safety and efficacy profile of esketamine as a sleep-aid in surgical contexts needs comprehensive evaluation. While esketamine’s rapid action and distinct mechanism present advantages, careful monitoring is essential, especially given its psychotropic properties. The study’s promising results lay the groundwork for larger-scale clinical trials to validate these findings and translate them into practice.
The role of oral microbiota as a biomarker for predicting postoperative sleep complications also emerges as a fascinating avenue. If specific microbial signatures associated with poor sleep can be identified, preemptive interventions might be formulated, such as targeted probiotics or microbiota modulation strategies tailored to individual patient profiles.
This integration of microbiota research with clinical pharmacology exemplifies a modern, holistic approach to medicine—recognizing that the human body functions as an interconnected ecosystem. Therapeutics like esketamine are thus not simply acting on isolated pathways but are part of a complex biological dialogue encompassing neurochemistry, immunity, and microbial symbiosis.
In practical terms, this study could transform anesthesia and perioperative care practices. Anesthesiologists and surgeons may one day incorporate esketamine protocols not only for analgesia and mood stabilization but also for optimizing sleep health, thereby improving patient outcomes and satisfaction.
The discovery also resonates beyond sleep medicine. Given the extensive relationship between sleep and mental health, especially depression and anxiety disorders, this work posits esketamine as a multifaceted agent capable of addressing intertwined aspects of patient wellbeing through combined neurological and microbiological mechanisms.
Future research inspired by this study might also explore how other anesthetic or psychiatric drugs interact with the microbiome and affect sleep and recovery trajectories. Such interdisciplinary efforts will be crucial for developing next-generation personalized therapies that harness the full spectrum of biological networks underpinning human health.
In conclusion, the study by Li et al. represents a paradigm shift, demonstrating that esketamine’s efficacy extends beyond traditional neurotransmitter targets to involve the oral microbiome in mitigating postoperative sleep disturbances. This breakthrough paves the way for innovative treatments that amalgamate microbiology, pharmacology, and neuroscience to enhance postoperative care and tackle the pervasive issue of sleep disorders.
Subject of Research: Esketamine’s role in preventing postoperative sleep disturbances in patients with preoperative sleep disorders, with a focus on oral microbiota interactions.
Article Title: Esketamine prevents postoperative sleep disturbance in patients with preoperative sleep disorders: a role for oral microbiota.
Article References:
Li, XY., Qiu, D., Du, N. et al. Esketamine prevents postoperative sleep disturbance in patients with preoperative sleep disorders: a role for oral microbiota. Transl Psychiatry 15, 501 (2025). https://doi.org/10.1038/s41398-025-03705-9
Image Credits: AI Generated
DOI: 10.1038/s41398-025-03705-9 (24 November 2025)
