Integrative Multi-omics Analysis of the Microbiome and Metabolome in Bronchoalveolar Lavage Fluid from Patients with Early-stage Lung Cancer

Jiajun XieNengyang ZhuWeiguo Xu^*

• Department of Respiratory and Critical Care Medicine, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, China

Lung cancer is a significant health concern that poses a considerable threat to human health and quality of life. In order to enhance the prognosis of patients with lung cancer, we conducted a combined analysis of 16S rDNA gene sequencing of alveolar lavage fluid and LC-MS metabolomics research, with the objective of identifying biomarkers in patients with early-stage lung cancer presenting as SPN. A comparison of the benign nodule group and the early-stage lung cancer patients revealed that the phylum-level Bacteroidetes and the genus-level Chryseobacterium and Delftia were more abundant in the latter group. Additionally, the Fusobacteriales might serve as a predictive marker for the diagnosis of early-stage lung cancer. In the context of metabolomics, the early-stage lung cancer was found to be characterised by elevated levels of specific metabolites, including Alternariol, dTMP, Oxymatrine, Gedunin, PC 36:4. Conversely, reductions in other metabolites, such as LPC O-24:0, PC 18:2_18:3, PC 19:2_19:2, Cholecalciferol and T-2 Triol, were also observed. Correlation analyses demonstrated that alveolar lavage microorganisms were closely associated with differential metabolites. Specifically, reductions in Cholecalciferol were associated with a variety of high-abundance flora and involved in vitamin digestion and absorption pathways. Furthermore, reductions in cholecalciferol may serve as a robust predictor of early-stage lung cancer. These findings provide new predictive biomarkers for earlystage lung cancer manifested by SPN, which is clinically important and requires further study of the potential mechanisms of action and function of the targets.