Lung virome convergence precedes hospital-acquired pneumonia in intubated critically ill patients
Hospital-acquired pneumonia (HAP) is one of the most common nosocomial infections, leading to significant morbidity and mortality in critically ill patients. HAP is previously associated with dysbiosis of the microbiota. However, the composition of the lung virome and its role in HAP pathogenesis remain unclear. Here, we longitudinally analyze the endotracheal virome in 87 critically ill patients, including 48 with HAP. Within the virome dominated by Caudoviricetes, a decrease in viral beta-diversity toward a bacteriophage-dominated signature and a distinct viral-bacterial interactome is observed 5-4 days before HAP onset. Lung virome composition, viral convergence before HAP onset, and conservation of 18% of the bacteriophage signature are validated in an external cohort of 40 patients. In silico causal inference further identifies bacteriophages associated with Streptococcus and Prevotella as a key regulator of HAP onset. These findings suggest an uncovered pathophysiological mechanism of HAP with virome involvement in lung microbiota dysbiosis. The discovery and validation studies are registered at ClinicalTrials.gov (NCT02003196 and NCT04793568).
Authors
- Louise Castain
- Mélanie Petrier (ORCID: https://orcid.org/0000-0001-5844-9693)
- Grégory Destras (ORCID: https://orcid.org/0000-0001-6817-7118)
- Cécile Poulain (ORCID: https://orcid.org/0009-0000-6169-5713)
- Gwendolyne Burfin
- Céline Bressollette‐Bodin (ORCID: https://orcid.org/0000-0001-5175-0790)
- Antoine Roquilly (ORCID: https://orcid.org/0000-0002-1029-6242)
- Hussein Anani (ORCID: https://orcid.org/0000-0003-4047-2013)
- Florian Pierre Martin (ORCID: https://orcid.org/0000-0002-5968-5484)
- Robert P. Dickson (ORCID: https://orcid.org/0000-0002-6875-4277)
- Laurence Josset (ORCID: https://orcid.org/0000-0002-7158-1186)
- Quentin Semanas
- Simon Bulteau (ORCID: https://orcid.org/0000-0002-0133-5799)
Institutions
- Université Claude Bernard Lyon 1 (FR)
- École Normale Supérieure de Lyon (FR)
- Centre National de la Recherche Scientifique (FR)
- Inserm (FR)
- University of Michigan (US)
- Hospices Civils de Lyon (FR)
- Institut de Transplantation Urologie en Nephrologie (FR)
- Centre d'Investigation Clinique de Nantes (FR)
- Centre International de Recherche en Infectiologie (FR)
- Nantes Université (FR)
Publication Details
- Journal
- Cell Reports Medicine
- Published
- 2025-09-01
- DOI
- https://doi.org/10.1016/j.xcrm.2025.102289
- Citations
- 4
- Primary Topic
- Bacteriophages and microbial interactions
- Type
- article
- Field-Weighted Citation Impact
- 6.87
Funders
- European Commission
- Horizon 2020 Framework Programme
- HORIZON EUROPE Framework Programme