Department of Clinical Microbiology, Zibo City Key Laboratory of Respiratory Infection and Clinical Microbiology, Zibo City Engineering Technology Research Center of Etiology Molecular Diagnosis, Zibo Municipal Hospital, Zibo, 255400, China.
Shandong University-Zibo Municipal Hospital Research Center of Human Microbiome and Health, Zibo, 255400, China.
BMC Pulm Med. 2024 Jan 2;24(1):1. doi: 10.1186/s12890-023-02825-6.
Lung cancer (LC) is one of the most devastating diseases worldwide, there is growing studies confirm the role of impaired lung function in LC susceptibility. Moreover, gut microbiota dysbiosis is associated with LC severity. Whether alterations in gut microbiota and metabolites are associated with long-term lung dysfunction in LC patients remain unclear. Our study aimed to analyze the risk factors in LC patients with impaired pulmonary function based on the characteristics of the gut microbiome and metabolites.
Fecal samples from 55 LC patients and 28 benign pulmonary nodules patients were collected. Pulmonary ventilation function was graded according to the American Thoracic Society/ European Respiratory Society (ATS/ERS) method. LC patients were divided into 3 groups, including 20 patients with normal lung ventilation, 23 patients with mild pulmonary ventilation dysfunction and 12 patients with moderate or above pulmonary ventilation dysfunction. The fecal samples were analyzed using 16 S rRNA gene amplicon sequencing and metabolomics.
The gut microbiome composition between LC patients and benign pulmonary nodules patients presented clearly differences based on Partial Least Squares Discriminant Analysis (PLS-DA). Pulmonary ventilation function was positively correlated with LC tumor stage, the richness and diversity of the gut microbiota in LC patients with moderate or above pulmonary ventilation dysfunction increased significantly, characterized by increased abundance of Subdoligranulum and Romboutsia. The metabolomics analysis revealed 69 differential metabolites, which were mainly enriched in beta-Alanine metabolism, styrene degradation and pyrimidine metabolism pathway. The area under the curve (AUC) combining the gut microbiome and metabolites was 90% (95% CI: 79-100%), indicating that the two species and four metabolites might regarded as biomarkers to assess the prediction of LC patients with impaired pulmonary function.
Our results showed that microbiome and metabolomics analyses provide important candidate to be used as clinically diagnostic biomarkers and therapeutic targets related to lung cancer with impaired pulmonary function.
肺癌（LC）是全球最具破坏性的疾病之一，越来越多的研究证实肺功能受损在 LC 易感性中的作用。此外，肠道微生物群落失调与 LC 的严重程度有关。LC 患者长期肺功能障碍是否与肠道微生物群落和代谢物的改变有关尚不清楚。我们的研究旨在根据肠道微生物群落和代谢物的特征，分析肺功能受损的 LC 患者的危险因素。
收集了 55 例 LC 患者和 28 例良性肺结节患者的粪便样本。根据美国胸科学会/欧洲呼吸学会（ATS/ERS）方法对肺通气功能进行分级。将 LC 患者分为 3 组，包括 20 例肺通气功能正常患者、23 例轻度肺通气功能障碍患者和 12 例中度或以上肺通气功能障碍患者。采用 16S rRNA 基因扩增子测序和代谢组学方法分析粪便样本。
基于偏最小二乘判别分析（PLS-DA），LC 患者和良性肺结节患者的肠道微生物群落组成呈现明显差异。肺通气功能与 LC 肿瘤分期呈正相关，中度或以上肺通气功能障碍的 LC 患者肠道微生物群落的丰富度和多样性显著增加，Subdoligranulum 和 Romboutsia 的丰度增加。代谢组学分析共发现 69 个差异代谢物，主要富集在β-丙氨酸代谢、苯乙烯降解和嘧啶代谢途径。联合肠道微生物群和代谢物的曲线下面积（AUC）为 90%（95%CI：79-100%），表明两种细菌和四种代谢物可能作为评估 LC 患者肺功能受损的预测标志物。
我们的研究结果表明，微生物组和代谢组学分析为作为与肺功能受损相关的 LC 的临床诊断生物标志物和治疗靶点提供了重要的候选物。
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