Personalized Treatment Selection for Digital Eating Disorder Interventions: A Proof-of-Concept for the Personalized Advantage Index.

Racemic ketamine has long been used for anesthesia, analgesia, and sedation [], and clinical trials have established its rapid antidepressant effects in treatment-resistant patients with major depressive disorder (MDD) [–]. By non-competitively blocking -methyl-D-aspartate receptors (NMDARs)—particularly on inhibitory interneurons—ketamine transiently enhances cortical glutamatergic transmission, activates synaptogenic signaling cascades, and produces antidepressant effects within hours that can persist for days []. Beyond psychiatry, ketamine and its ()-enantiomer, esketamine, are increasingly used for acute pain control and perioperative management []. Recent studies have expanded the understanding of ketamine beyond its central nervous system actions, revealing important effects on systemic inflammation and organ protection, partly associated with interactions involving the gut microbiota, microbial metabolites, and gut-derived immune-cell trafficking [–]. Much of this work focuses on two major gut-organ communication pathways: the gut–brain and gut–lung axes [–]. The gut–brain axis regulates central nervous system (CNS) function through neural, immune, and metabolic signaling, whereas the gut–lung axis describes how gut-derived microbes, metabolites, and immune cells influence pulmonary immunity and pathology [, , ]. Dysregulation of these axes can promote neuroinflammation and lung injury, contributing to disorders such as depression, chronic obstructive pulmonary disease (COPD), and acute respiratory distress syndrome (ARDS) [, , –]. In parallel, alterations in microbial metabolites have been linked to metabolic, cardiovascular, and neurodegenerative diseases [, ], and accumulating evidence suggests that ketamine and its enantiomers can reshape gut microbial communities and their metabolic outputs [, ]. Given ketamine’s anti-inflammatory and immunoregulatory properties [, , ], this review systematically examines how ketamine and its enantiomers influence the gut–brain and gut–lung axes, with particular emphasis on changes in gut microbiota composition, microbial metabolites, and intestinal immune-cell migration.