非吸烟者中早期肺腺癌（ES-LUAD）的发病率正在稳步上升。先前的研究已经发现肺癌患者的肠道微生物群存在失调。然而，患有 ES-LUAD 的非吸烟者的局部微生物特征仍然很大程度上未知。在本研究中，我们系统地描述了局部微生物群落及其相关特征，以实现早期干预。前瞻性收集 ES-LUAD 样本（46 例）及其相应的肿瘤邻近正常组织（41 例）以及正常肺对自发性气胸患者（42 例）肺大泡附近的组织样本进行超深度宏基因组测序、宿主转录组测序和蛋白质组测序。使用 Spearman 相关系数对获得的组学数据进行个体分析和综合分析。我们同时检测肺组织中细菌、真菌和病毒的存在。 ES-LUAD 的微生物特征与 NAT 相似，但与健康对照 (HC) 存在显着差异，其特点是物种多样性总体下降。 ES-LUAD 患者表现出局部微生物失调，表明某些微生物物种具有潜在致病性。通过多组学相关性，观察到宿主和当地微生物群落之间复杂的局部串扰。此外，我们使用多组学数据确定了 Mmethyloversatilis discipulorum 和 GOLM1 在转录和蛋白质水平上存在显着的正相关性 (rho > 0.6)。该相关轴可能与预后相关。最后，由六种细菌标记物组成的诊断模型成功实现了 ES-LUAD 患者和 HC 患者之间的精确区分。我们的研究描述了 ES-LUAD 患者的微生物谱，并提供了肺部微生物群变化及其与宿主相互作用的证据，增强对 ES-LUAD 致病机制的理解。纳入肺部微生物群的特定模型可以作为区分 ES-LUAD 和 HC 的潜在诊断工具。© 2024。作者。

The incidence of early-stage lung adenocarcinoma (ES-LUAD) is steadily increasing among non-smokers. Previous research has identified dysbiosis in the gut microbiota of patients with lung cancer. However, the local microbial profile of non-smokers with ES-LUAD remains largely unknown. In this study, we systematically characterized the local microbial community and its associated features to enable early intervention.A prospective collection of ES-LUAD samples (46 cases) and their corresponding normal tissues adjacent to the tumor (41 cases), along with normal lung tissue samples adjacent to pulmonary bullae in patients with spontaneous pneumothorax (42 cases), were subjected to ultra-deep metagenomic sequencing, host transcriptomic sequencing, and proteomic sequencing. The obtained omics data were subjected to both individual and integrated analysis using Spearman correlation coefficients.We concurrently detected the presence of bacteria, fungi, and viruses in the lung tissues. The microbial profile of ES-LUAD exhibited similarities to NAT but demonstrated significant differences from the healthy controls (HCs), characterized by an overall reduction in species diversity. Patients with ES-LUAD exhibited local microbial dysbiosis, suggesting the potential pathogenicity of certain microbial species. Through multi-omics correlations, intricate local crosstalk between the host and local microbial communities was observed. Additionally, we identified a significant positive correlation (rho > 0.6) between Methyloversatilis discipulorum and GOLM1 at both the transcriptional and protein levels using multi-omics data. This correlated axis may be associated with prognosis. Finally, a diagnostic model composed of six bacterial markers successfully achieved precise differentiation between patients with ES-LUAD and HCs.Our study depicts the microbial spectrum in patients with ES-LUAD and provides evidence of alterations in lung microbiota and their interplay with the host, enhancing comprehension of the pathogenic mechanisms that underlie ES-LUAD. The specific model incorporating lung microbiota can serve as a potential diagnostic tool for distinguishing between ES-LUAD and HCs.© 2024. The Author(s).