Microbiome-Informed Precision Electroconvulsive Therapy: Oral-Gut-Immune Signatures and Seizure Biology as Candidate...

Background/Objectives: Electroconvulsive therapy (ECT) is among the most effective treatments for severe major depression, treatment-resistant depression, psychotic and bipolar depression, catatonia, and selected psychotic disorders. Yet response, remission, seizure adequacy, and cognitive tolerability remain difficult to predict for an individual patient. This review examines whether oral and gut microbial signatures can inform precision ECT as contextual biological markers, rather than as standalone explanations of ECT efficacy. Methods: A structured narrative PubMed/MEDLINE search was conducted on 1 May 2026 and supplemented by targeted manual searches of Crossref, Google Scholar, journal websites, and reference lists updated through 17 May 2026. Evidence was grouped as direct human ECT-microbiome studies, indirect human ECT biomarker studies, preclinical electroconvulsive shock (ECS) studies, and mechanistic microbiome-gut-brain literature. Results: Direct human ECT-microbiome evidence remains very limited and currently consists of two small prospective cohorts with sufficient microbiome data, totaling approximately 25 patients across studies, plus one single-patient case report. In severe or treatment-resistant depression, a pilot oral microbiome study with sufficient microbiological data from 14 patients reported higher pre-treatment oral alpha diversity in responders than in non-responders, without a consistent global oral microbiome shift after ECT. In schizophrenia, a small stool microbiome cohort of 11 patients suggested that baseline Bifidobacterium and Lactobacillus proportions may relate to symptom improvement, although sample size and confounding preclude firm inference. Conclusions: Microbiome-informed precision ECT remains a biologically plausible research direction, but current human evidence supports only cautious evaluation of baseline microbial context as a candidate predictor, not clinical microbiome-guided ECT, mediation, or microbiome-modifying intervention. The strongest current biological bridge comes from inflammatory markers, particularly baseline CRP and IL-6. Preclinical ECS studies support gut inflammatory, motility and vagal mechanisms, but they cannot substitute for human validation.