社区获得性肺炎（CAP）是全球范围内最常见的感染性疾病之一，不仅会引发局部组织炎症性损伤，还会引发全身免疫反应失衡，严重威胁患者生命安全。近年来，流感病毒（IAV）感染引发的肺炎事件也屡见不鲜，其致病性不仅与病毒复本身有关，还包括随后过度活跃、持续失调的免疫炎症反应，加重了肺损伤并导致较差的远期预后。
本课题涉及两部分内容：（1）在临床队列中，表征CAP 患者从急性期到恢复期多组学特征，系统探究感染恢复过程中的宿主基因转录动态变化以及上呼吸道微生物群的结构变化；（2）在小鼠流感病毒感染模型中，探究外源性鼠李糖乳杆菌（LGG）作为一种可能的微生态干预手段，改善肺部炎症环境稳态及代谢通路重塑的潜在机制。
在 CAP 研究中，通过时间序列分析，发现能量代谢、凝血功能及免疫反应是恢复过程中值得关注的三类事件。在上呼吸道微生物组研究中，发现菌群失调的恢复是更为缓慢的过程。进一步结合宿主转录-微生物关联分析发现，特定菌属与宿主代谢或免疫信号调控紧密相关。对于鼠李糖乳杆菌干预模型，实验结果表明干预可降低流感病毒感染的小鼠病毒载量，增强T 细胞反应，调节特定功能性代谢物，增强宿主免疫应答。
本研究通过多组学分析，结合CAP临床样本分析与LGG 预防性干预模型，从宏观到微观层面探索肺炎的复杂机制，并揭示LGG 在宿主免疫代谢调控中的潜力，为肺炎防治提供理论支撑。

Community-acquired pneumonia (CAP) is one of the most prevalent infectious diseases worldwide. Its acute infection not only causes significant inflammatory damage to airway tissues but also triggers imbalanced systemic immune responses, posing severe threats to patients. In recent years, pneumonia caused by influenza A virus (IAV) infection has become increasingly common. The pathogenicity of IAV is not only driven by viral replication itself but also by the subsequent hyperactive and persistently dysregulated immune-inflammatory responses, which exacerbate lung injury and lead to poor long-term outcomes.
This study encompasses two main research components: (1) Characterizing the multi-omics features of CAP patients from the acute phase to the recovery phase in a clinical cohort, systematically investigating the transcriptional dynamics of host genes and structural changes in the upper respiratory microbiota during the infection process; (2) Exploring the protective effects of intranasal administration of exogenous Lactobacillus rhamnosus GG (LGG) in a mouse IAV infection model, including its impact on viral control in the lungs, inflammatory homeostasis, and metabolic pathway remodeling.
In the CAP study, time-series analysis revealed that energy metabolism, coagulation function, and immune responses were three critical processes during recovery. In the upper respiratory microbiome analysis, the restoration of microbiota dysbiosis was found to be a slow process. Further transcriptome-microbiome correlation analysis identified that specific bacterial genera strongly associated with host metabolic or immune signal regulation. In the LGG intervention model, experimental results demonstrated that LGG administration reduced viral load in IAV-infected mice, enhanced T-cell responses, and modulated specific functional metabolites (e.g., itaconic acid) to improve host immune responses.
Through multi-omics analysis, combining CAP clinical sample analysis with the LGG preventive intervention model, this study explored the complex mechanisms of pneumonia from a macro- to micro-level perspective. Furthermore, it uncovered the potential of LGG in host immune-metabolic regulation, providing theoretical insights for pneumonia prevention and treatment.