Abstract
BACKGROUND: Lung cancer (LC) is one of the most aggressive, prevalent and fatal malignancies. Gut microbes and their associated metabolites are thought to cause and modulate LC development, albeit influenced by the host genetic make-up and environment. Herein, we identified and classified gut microbiota and serum metabolites associated with LC. METHODS: Stool samples were collected from 41 LC patients and 40 healthy volunteers. The gut microbiota was analyzed using 16S rRNA gene sequencing. Serum samples were collected from the same LC patients (n=30) and healthy volunteers (n=30) and serum metabolites were analyzed using liquid chromatography-mass spectrometry (LC-MS). Microbiome and metabolome data were analyzed separately and integrated for combined analysis using various bioinformatics methods. RESULTS: Serum metabolomics uncovered 870 metabolites regulated in 76 metabolic pathways in both groups. Microbial diversity analyses identified 15967 operational taxonomic units (OTUs) in groups. Of these, the abundance of 232 OTUs was significantly different between HC and LC groups. Also, serum levels of glycerophospholipids (LysoPE 18:3, LysoPC 14:0, LysoPC 18:3), Imidazopyrimidines (Hypoxanthine), AcylGlcADG 66:18; AcylGlcADG (22:6/22:6/22:6) and Acylcarnitine 11:0 were substantially different between HC and LC groups. Combined analysis correlated LC-associated microbes with metabolites, such as Erysipelotrichaceae_UCG_003, Clostridium and Synergistes with glycerophospholipids. CONCLUSIONS: There is an intricate relationship between gut microbiome and levels of several metabolites such as glycerophospholipids and imidazopyrimidines. Microbial-associated metabolites are potential diagnostic biomarkers and therapeutic targets for LC.