Ketamine, Sleep, and Oral Bacteria – A Microbial Mystery

Surgery is a trauma that wrecks sleep, and for vulnerable patients, Post-Operative Sleep Disturbance (PSD) is a serious complication linked to delirium, increased pain, and slowed recovery. In this episode, we dive into a fascinating study that connects three seemingly unrelated dots: ketamine, sleep, and the oral microbiome. Researchers treated 130 high-risk surgical patients with a continuous low-dose infusion of esketamine. The clinical results were striking: the rate of PSD dropped from 65% in the control group to just 43% in the esketamine group. Patients reported significantly better sleep quality and required far fewer opioids like hydromorphone. But the real surprise was found in their saliva. The study revealed that esketamine treatment actively reshaped the oral microbial community—boosting beneficial bacteria like Streptococcus while suppressing groups like Bacteroidota that were linked to poor sleep. Why would an IV anesthetic change mouth bacteria? We explore the leading theories: Systemic Anti-Inflammation: Surgery floods the body with pro-inflammatory cytokines (a "systemic fire"). Ketamine’s powerful anti-inflammatory properties may calm this environment, making the host less hospitable to stress-related microbes. The Gut-Oral Axis: Ketamine may influence the gut microbiome, with effects rippling up to the mouth to stabilize the body's entire ecosystem. This research challenges us to rethink how psychiatric drugs work—not just by hitting receptors in the brain, but by restoring ecological balance to the nerves, immune system, and the trillions of microbes that live within us. Reference: Li, X.-Y., Qiu, D., Du, N., Hashimoto, K., Wang, X.-M., & Yang, J.-J. (2025). Esketamine prevents postoperative sleep disturbance in patients with preoperative sleep disorders: A role for oral microbiota. Translational Psychiatry, 15(1), 501. https://doi.org/10.1038/s41398-025-03705-9