Identification of functional bacterial-viral pneumotypes associated with airway inflammation and all-cause mortality in critically ill patients
Abstract
Alterations in lung virome and bacteriome compositions have been associated with hospital-acquired pneumonia in critically ill patients, but data on lung microbiome functions underlying progression to severe complications remain unclear. Here, we analyse 184 endotracheal aspirates (ETAs) collected in 94 intubated critically ill patients enrolled in a clinical trial (NCT04793568). Combining viral-metagenomics with metatranscriptomics analyses, we identify a high-risk functional pneumotype observed before the onset of hospital-acquired pneumonia and associated with lung inflammation and mortality. This unfavourable pneumotype is characterised by enrichment in virulent Streptococcus-bacteriophages and temperate Klebsiella-bacteriophages, decreased transcriptional activity of commensal taxa such as Streptococcus and Alloprevotella, and increased transcriptional activity of Klebsiella pneumoniae. Machine-learning models define two-viral- and four-bacterial-factor signatures predicting unfavourable pneumotype (AUC 0.8 and 0.7, respectively). Validation in an independent cohort (NCT02003196) of 117 ICU patients (239 ETAs) demonstrates the robustness of the association of these signatures with the risk of mortality. Causal inference identifies virulent bacteriophages associated with Streptococcus and host genes including IL18R1, ADM and PTX3, as key regulators of severe lung dysbiosis linked to mortality in critically ill patients.
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BibTeX
@article{anani2026identification,
title = {{Identification of functional bacterial-viral pneumotypes associated with airway inflammation and all-cause mortality in critically ill patients}},
author = {Hussein Anani and Grégory Destras and Quentin Semanas and Florian P. Martin and Mélanie Petrier and Eva Oddoux and Gwendolyne Burfin and Simon Bulteau and Cécile Poulain and Debajyoti Sinha and Ana Motos and Victor Gourain and Lise Cremet and Emmanuel Montassier and Céline Bressollette-Bodin and Antoine Roquilly and Laurence Josset},
journal = {Nature Communications},
year = {2026},
month = sep,
doi = {10.1038/s41467-026-78146-z},
url = {https://www.nature.com/articles/s41467-026-78146-z},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Identification of functional bacterial-viral pneumotypes associated with airway inflammation and all-cause mortality in critically ill patients
AU - Hussein Anani
AU - Grégory Destras
AU - Quentin Semanas
AU - Florian P. Martin
AU - Mélanie Petrier
AU - Eva Oddoux
AU - Gwendolyne Burfin
AU - Simon Bulteau
AU - Cécile Poulain
AU - Debajyoti Sinha
AU - Ana Motos
AU - Victor Gourain
AU - Lise Cremet
AU - Emmanuel Montassier
AU - Céline Bressollette-Bodin
AU - Antoine Roquilly
AU - Laurence Josset
PY - 2026
DA - 2026/09/30
JO - Nature Communications
DO - 10.1038/s41467-026-78146-z
UR - https://www.nature.com/articles/s41467-026-78146-z
AB - Alterations in lung virome and bacteriome compositions have been associated with hospital-acquired pneumonia in critically ill patients, but data on lung microbiome functions underlying progression to severe complications remain unclear. Here, we analyse 184 endotracheal aspirates (ETAs) collected in 94 intubated critically ill patients enrolled in a clinical trial (NCT04793568). Combining viral-metagenomics with metatranscriptomics analyses, we identify a high-risk functional pneumotype observed before the onset of hospital-acquired pneumonia and associated with lung inflammation and mortality. This unfavourable pneumotype is characterised by enrichment in virulent Streptococcus-bacteriophages and temperate Klebsiella-bacteriophages, decreased transcriptional activity of commensal taxa such as Streptococcus and Alloprevotella, and increased transcriptional activity of Klebsiella pneumoniae. Machine-learning models define two-viral- and four-bacterial-factor signatures predicting unfavourable pneumotype (AUC 0.8 and 0.7, respectively). Validation in an independent cohort (NCT02003196) of 117 ICU patients (239 ETAs) demonstrates the robustness of the association of these signatures with the risk of mortality. Causal inference identifies virulent bacteriophages associated with Streptococcus and host genes including IL18R1, ADM and PTX3, as key regulators of severe lung dysbiosis linked to mortality in critically ill patients.
SN - 2041-1723
ER -