Fig. 4: Lung dysbiosis features and clusters predict 60-day survival.

A, B: Forest plots of effect sizes (point estimates and 95% confidence intervals) for dysbiosis features (Shannon index, bacterial load, anaerobe and pathogen abundance) in three different models: (i) mixed linear regression models with random patient intercepts for the longitudinal change of dysbiosis features during follow-up sampling, (ii) the age-adjusted hazards ratios from Cox-proportional hazards models for the baseline values of each feature on 60-day survival, and (iii) joint-modeling with adjusted beta-coefficient for the effect of each longitudinally-measured feature on survival. Joint modeling showed that pathogen abundance in the oral compartment and anaerobe abundance in the lung compartment had borderline statistically significant effects on 60-day survival. Joint-models for bacterial load by qPCR did not converge due to low number of longitudinal measurements. C. Kaplan-Meier curves for 60-day survival from intubation stratified by oral (A), lung (B) and gut (C) bacterial DMM clusters. The Low-Diversity lung DMM cluster was independently predictive of worse survival (adjusted Hazard Ratio = 2.22 (1.0.7-4.63), Cox regression p = 0.03), following adjustment for age, sex, history of COPD, immunosuppression, severity of illness by sequential organ failure assessment (SOFA) scores and host-response subphenotypes. Longitudinal analysis of lung DMM clusters showed that patients who remained in the low diversity cluster from the baseline to the middle interval (“Low Diversity Persisters”) had significantly worse survival than other patients with available follow-up samples (age-adjusted HR = 2.73 [1.19–6.42], Cox regression p = 0.02). Source data are provided as a Source Data file. Displayed data include 380 oral, 393 lung and 216 gut samples from ICU patients obtained at baseline.