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

Lizhe Hong; Lijun Suo; Kang Chang; Hongyun Cao; Jiahui Luan; Fuxin Zhang; Xiaofeng Yu; Xiaohui Zou; Bo Liu; Bin Cao

doi:10.1016/j.bsheal.2025.05.004

Biosafety and Health (Jun 2025)

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

Lizhe Hong,
Lijun Suo,
Kang Chang,
Hongyun Cao,
Jiahui Luan,
Fuxin Zhang,
Xiaofeng Yu,
Xiaohui Zou,
Bo Liu,
Bin Cao

Affiliations

Lizhe Hong: Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China; National Center for Respiratory Medicine, State Key Laboratory of Respiratory Health and Multimorbidity, National Clinical Research Center for Respiratory Diseases, Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Laboratory of Clinical Microbiology and Infectious Diseases, Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing 100029, China
Lijun Suo: Department of Clinical Microbiology, Pulmonary and Critical Care Medicine, Zibo City Key Laboratory of Respiratory Infection and Clinical Microbiology, Zibo City Engineering Technology Research Center of Etiology Molecular Diagnosis, Zibo Municipal Hospital, Zibo 255013, China
Kang Chang: National Center for Respiratory Medicine, State Key Laboratory of Respiratory Health and Multimorbidity, National Clinical Research Center for Respiratory Diseases, Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Laboratory of Clinical Microbiology and Infectious Diseases, Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing 100029, China
Hongyun Cao: Department of Clinical Microbiology, Pulmonary and Critical Care Medicine, Zibo City Key Laboratory of Respiratory Infection and Clinical Microbiology, Zibo City Engineering Technology Research Center of Etiology Molecular Diagnosis, Zibo Municipal Hospital, Zibo 255013, China
Jiahui Luan: Department of Clinical Microbiology, Pulmonary and Critical Care Medicine, Zibo City Key Laboratory of Respiratory Infection and Clinical Microbiology, Zibo City Engineering Technology Research Center of Etiology Molecular Diagnosis, Zibo Municipal Hospital, Zibo 255013, China
Fuxin Zhang: Department of Clinical Microbiology, Pulmonary and Critical Care Medicine, Zibo City Key Laboratory of Respiratory Infection and Clinical Microbiology, Zibo City Engineering Technology Research Center of Etiology Molecular Diagnosis, Zibo Municipal Hospital, Zibo 255013, China
Xiaofeng Yu: Department of Clinical Microbiology, Pulmonary and Critical Care Medicine, Zibo City Key Laboratory of Respiratory Infection and Clinical Microbiology, Zibo City Engineering Technology Research Center of Etiology Molecular Diagnosis, Zibo Municipal Hospital, Zibo 255013, China
Xiaohui Zou: National Center for Respiratory Medicine, State Key Laboratory of Respiratory Health and Multimorbidity, National Clinical Research Center for Respiratory Diseases, Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Laboratory of Clinical Microbiology and Infectious Diseases, Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing 100029, China; Corresponding authors: Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing 100029, China (X. Zou and B. Cao); Department of Clinical Microbiology, Pulmonary and Critical Care Medicine, Zibo Municipal Hospital, Zibo 255013, China (B. Liu).
Bo Liu: Department of Clinical Microbiology, Pulmonary and Critical Care Medicine, Zibo City Key Laboratory of Respiratory Infection and Clinical Microbiology, Zibo City Engineering Technology Research Center of Etiology Molecular Diagnosis, Zibo Municipal Hospital, Zibo 255013, China; Department of Pulmonary and Critical Care Medicine, Shandong Institute of Respiratory Diseases, The First Affiliated Hospital of Shandong First Medical University, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan 250014, China; Corresponding authors: Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing 100029, China (X. Zou and B. Cao); Department of Clinical Microbiology, Pulmonary and Critical Care Medicine, Zibo Municipal Hospital, Zibo 255013, China (B. Liu).
Bin Cao: Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China; National Center for Respiratory Medicine, State Key Laboratory of Respiratory Health and Multimorbidity, National Clinical Research Center for Respiratory Diseases, Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Laboratory of Clinical Microbiology and Infectious Diseases, Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing 100029, China; Corresponding authors: Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing 100029, China (X. Zou and B. Cao); Department of Clinical Microbiology, Pulmonary and Critical Care Medicine, Zibo Municipal Hospital, Zibo 255013, China (B. Liu).

DOI: https://doi.org/10.1016/j.bsheal.2025.05.004
Journal volume & issue: Vol. 7, no. 3
pp. 152 – 165

Abstract

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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 < 0.05). CAP increased the relative abundance of Streptococcus, Veillonella, and Peptostreptococcus, while decreasing that of Haemophilus, Neisseria, and Porphyromonas. Integrated analysis of host response and oropharyngeal microbiome revealed that the relative abundance of Haemophilus, Neisseria, Porphyromonas, and Stomatobaculum were positively related to mitochondrial structure and function pathways, whereas the relative abundance of Prevotella declined over time in patients and positively correlated with anti-pathogen and interferon signaling pathways. These results underscore the persistent impact of CAP on both host immunity and oropharyngeal microbiome, even months after infection, emphasizing the need for long-term follow-up and targeted strategies to facilitate full recovery and restore homeostasis.

Published in Biosafety and Health

ISSN: 2590-0536 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Internal medicine: Infectious and parasitic diseases; Medicine: Public aspects of medicine
Website: https://www.journals.elsevier.com/biosafety-and-health/

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