Respiratory Virome Dynamics in Lower Respiratory Tract Infections with and without Respiratory Failure
Lower respiratory tract infections (LRTIs) are a significant cause of morbidity and mortality worldwide, with the respiratory microbiome playing a pivotal role in disease pathogenesis. Elucidating the composition of the microbial community within the lower respiratory tract of infected individuals is essential for the advancement of precision medicine approaches. In this study, we employed metagenomic sequencing of bronchoalveolar lavage fluid to compare the virome and bacterial microbiome of patients with LRTI to those of non-LRTI controls. While the ACE index revealed significant viral a-diversity differences between groups, bacterial communities showed no distinct a/ß-diversity patterns and differential taxonomic groups via PCoA, NMDS, ANOSIM, or LEfSe analyses. Additionally, patients experiencing respiratory failure   in LRTI group exhibited distinct viral taxonomic profiles, with Lentivirus, Human immunodeficiency virus 1, Phixviricota, Malgrandaviricetes, Petitvirales, Microviridae, unclassified Microviridae, and Microvirus sp. being identified as differential taxa by LEfSe analysis. However, viral alpha diversity (Shannon/Simpson/ACE/Chao indices) and beta diversity metrics (PCoA/NMDS/ANOSIM) in these patients were comparable to those without RF-complicating infections. Bacterial communities across clinical subgroups remained unstratified. Notably, uncultured human fecal virus inversely correlated with lymphocyte counts, while Streptococcus-associated bacteriophages were positively associated with C-reactive protein levels. These findings highlight the potential clinical relevance of viral microbiota alterations in LRTIs, particularly suggesting that specific viral signatures may reflect disease severity through interactions with host inflammatory responses.