Hong Lizhe, Suo Lijun, Chang Kang, Cao Hongyun, Luan Jiahui, Zhang Fuxin, Yu Xiaofeng, Zou Xiaohui, Liu Bo, Cao Bin
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.
Biosaf Health. 2025 May 15;7(3):152-165. doi: 10.1016/j.bsheal.2025.05.004. eCollection 2025 Jun.
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 ( < 0.05). CAP increased the relative abundance of , and , while decreasing that of , , and . Integrated analysis of host response and oropharyngeal microbiome revealed that the relative abundance of , , , and were positively related to mitochondrial structure and function pathways, whereas the relative abundance of 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.
社区获得性肺炎（CAP）是一个重大的全球健康问题，人们对宿主基因表达和呼吸道微生物群在疾病进展和恢复过程中的纵向变化了解有限。为了填补这一空白，我们纵向收集了CAP患者从入院到感染后4个月的外周血用于转录组分析，并收集口咽拭子用于微生物群分析。招募年龄和性别匹配的志愿者作为对照。我们观察到CAP患者对感染产生了快速、有效且适度的免疫反应。与对照组相比，凝血激活和线粒体功能障碍是CAP患者中表现出明显差异的显著途径，后者通过CAP患者外周血单核细胞（PBMC）中较低的三磷酸腺苷（ATP）水平得到验证。尽管转录扰动逐渐减少，但在随访期间并未完全恢复。同样，观察到口咽微生物群持续存在失调，其特征是α多样性显著降低且分类分布改变（<0.05）。CAP增加了 、 和 的相对丰度，同时降低了 、 和 的相对丰度。宿主反应和口咽微生物群的综合分析表明， 、 、 和 的相对丰度与线粒体结构和功能途径呈正相关，而 在患者中随时间下降且与抗病原体和干扰素信号通路呈正相关。这些结果强调了CAP对宿主免疫和口咽微生物群的持续影响，即使在感染数月后也是如此，强调了长期随访和针对性策略以促进完全恢复和恢复内环境稳定的必要性。
