Analyzing lung cancer risks in patients with impaired pulmonary function through characterization of gut microbiome and metabolites.

ABSTRACT

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.