Longitudinal profiling of host response and oropharyngeal respiratory microbiome reveals dynamic alterations during recovery from community-acquired pneumonia

Community-acquired pneumonia (CAP) is a major global health concern, with limited understanding of longitudinal changes in host gene expression and respiratory microbiome throughout disease progression and recovery. To address this gap, we longitudinally collected CAP patients’ peripheral blood for transcriptome and oropharyngeal swabs for microbiome analysis from admission to 4 months post infection. Age- and sex-matched volunteers were recruited as controls. We observed CAP patients mounted rapid, effective, and moderate immune responses against infection. Coagulation activation and mitochondrial dysfunction were the striking pathways showing distinct difference in CAP patients compared to controls, and the latter was validated by lower adenosine triphosphate (ATP) levels in the peripheral blood mononuclear cells (PBMCs) of CAP patients. Although transcriptional perturbations gradually decreased, they did not fully recover during the follow-up period. Similarly, persisting oropharyngeal microbiome dysbiosis was observed, characterized by significantly lower alpha diversity and altered taxonomy distribution (P