Multi-omics analysis of host airway responses in pediatric Mycoplasma pneumoniae pneumonia reveals potential mechanisms of disease exacerbation caused by co-infection
Zijie Li, Chunbo Hao, Gaijing Jia, Qiujing Liang, Qingmei Wang, Jing Wu, Yu Tang, Wangquan Ji, Yuanfang Shen, Fang Wang, Yaodong Zhang, Zhipeng Jin, Adong Shen, Yuefei Jin, Guangcai Duan
Abstract
Respiratory viral co-infections in children with Mycoplasma pneumoniae pneumonia (MPP) are common and cause severe clinical manifestations. However, the exact pathogenic mechanisms of MPP co-infections are still unclear. In this study, we conducted a large-scale clinical analysis of 3106 MPP patients to characterize co-infection patterns. Subsequent metabolomics, microbiomics, and cytokines analyses of the bronchoalveolar lavage fluid from 73 MPP cases were performed. Patients were divided into groups with single Mycoplasma pneumoniae (MP) infection and co-infection (including co-adenovirus [co-ADV] and co-influenza A virus [co-IAV]), while bronchial foreign body patients served as controls. Metabolomic profiling identified 616 differential metabolites between the single MP group and the co-infection group. Collectively, these metabolites contributed to the formation of a pro-inflammatory microenvironment in patients with co-infections. Notably, ADV co-infection induced profound pulmonary microbiota dysbiosis, characterized by selective depletion of Lactobacillus. Next, we observed a robust upregulation of CCL-family chemokines in patients co-infected with ADV, which showed a significant correlation with peripheral monocyte counts, suggesting that monocyte-driven inflammation may serve as a key mechanism for disease exacerbation. These findings demonstrate that co-infection (co-ADV and co-IAV) triggers a pro-inflammatory metabolic shift. Additionally, ADV co-infection specifically disrupts lung microbiota structure and increases CCL family chemokines.