Lung microbiome features associated with ICU delirium in mechanically ventilated patients: a secondary cohort...

Delirium in mechanically ventilated intensive care unit (ICU) patients is linked to inflammatory dysregulation, but whether the pulmonary microbiome contributes to delirium risk remains unclear.

We performed a secondary analysis of 132 mechanically ventilated adults from the MicroNAV cohort. Baseline bronchoalveolar lavage (BAL) samples collected within 12 h of intubation were profiled by 16S rRNA gene sequencing; total bacterial burden was quantified by droplet digital PCR (ddPCR; n = 125), and BAL cytokines were measured using a multiplex assay (n = 70). Concordant genus-level signals identified by four differential-abundance methods were aggregated into ecological scores and tested using logistic regression adjusted for age and Glasgow Coma Scale at intubation. Absolute abundance was estimated by multiplying relative abundance by ddPCR-derived bacterial burden.

Delirium was recorded in 45 patients (34.1%). Total bacterial DNA concentration was lower in patients with delirium (median 7419 vs 98,326 copies/μL, P = 0.001). A putative short-chain fatty acid (SCFA)-producing commensal score (Phocaeicola, Selenomonas, and Fretibacterium) was inversely associated with delirium in compositional analysis (OR 0.83, 95% CI 0.75-0.92, P < 0.001) and after ddPCR-anchored absolute quantification (OR 0.84, 95% CI 0.75-0.94, P = 0.002). This depletion extended to oral-core commensals (absolute OR 0.80, P < 0.001) and a pre-specified oral anaerobe score (absolute OR 0.82, P = 0.002). Opportunistic colonizers were enriched compositionally but not in absolute abundance (OR 1.10, P = 0.187). Commensal scores were positively associated with BAL IL-1β and TNF-α, whereas opportunistic-colonizer scores showed inverse associations.

Early pulmonary depletion of oral-derived commensals, particularly putative SCFA producers, was associated with ICU delirium. Prospective studies with standardized delirium assessment and functional metabolite measurements are needed.