ArticleMolecular psychiatry2026
Gut microbiota and blood biomarkers as correlating factors in patients with postoperative delirium: analysis of three prospective observational studies.
Article in Molecular psychiatry, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Postoperative delirium is associated with both gut microbiota alterations and Tau phosphorylation; however, how these factors interact and jointly contribute to postoperative delirium remains poorly understood. This prospective observational cohort study screened 491 patients aged ≥65 years undergoing elective laminectomy or hip or knee replacement under general or spinal anesthesia at Massachusetts General Hospital (2016-2020). The study aimed to assess the correlation between plasma Tau protein levels, specific gut microbiota, and the gut microbiota-derived metabolite indole-3-propionic acid (IPA) in participants with and without postoperative delirium. Exclusion criteria included major neurological disease, smoking history, sensory impairment, and recent antibiotic use. Delirium was assessed 24-48 h postoperatively. Out of 491 screened participants, 139 had blood biomarker data, and 86 had gut microbiota data included in the final analysis. Ten percent of the participants experienced postoperative delirium. Co-occurrence network analysis demonstrated that microbial interactions differed between postoperative delirium and non-postoperative delirium groups. Significant associations among gut microbiota, IPA, and Tau biomarkers were observed only in postoperative delirium participants. Additionally, three machine learning classifiers distinguished postoperative delirium cases from non-postoperative delirium cases with Area Under the Curve values above 50%. The results suggest that plasma Tau may interact with gut microbiota, and this interaction is associated with postoperative delirium, suggesting the involvement of a gut-blood-brain axis in postoperative delirium vulnerability. These findings implicate a microbiota-Tau interaction that may represent both a potential pathogenic mechanism and a therapeutic target for postoperative delirium pending confirmative studies. Furthermore, machine learning classifiers utilizing microbiome-derived features demonstrate a potential in distinguishing patients with and without postoperative delirium.
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