Abstract
BACKGROUND: Smoking is a significant risk factor for pancreatic ductal adenocarcinoma (PDAC). This study aimed to investigate the effects of smoking on the pancreatic microbiome and metabolome in resectable and unresectable male PDAC patients. METHODS: The pancreatic tissue samples were collected from resectable PDACs via surgery and unresectable PDACs via endoscopic ultrasound fine needle aspiration (EUS-FNA). Surgical samples obtained from 10 smoking and 6 non-smoking PDACs were measured by 16S ribosomal RNA (16S rRNA) gene sequencing and liquid chromatography-mass spectrometry (LC/MS). Fine needle aspiration (FNA) samples obtained from 20 smoking and 14 non-smoking PDACs were measured by 16S rRNA gene sequencing. RESULTS: From resectable to unresectable patients, the dominant genus in the pancreas changed from Achromobacter to Delftia. Smoking further altered the abundance of specific bacteria, mainly manifested as an increase of Slackia in surgical tumor tissue of the smoking group, and an enrichment of Aggregatibacter and Peptococcus in FNA samples of the smoking group. In tumor tissue, smoking caused an enrichment of the cancer-promoting cAMP signaling pathway and L-lactic acid. In paracancerous tissue, smoking also induced a detrimental disturbance in the pancreatic microbiome and metabolome, including an enrichment of Veillonella, Novosphingobium, Deinococcus, and 3-hydroxybutanoic acid, and a reduction of linoleic acid. Besides, the cancer-promoting L-lactic acid was negatively correlated with Faecalibacterium in tumor tissue based on the correlation analysis. CONCLUSION: There were differences in the pancreatic microbiome of PDAC patients at different stages, and smoking can further disrupt the pancreatic microbiome and metabolism in PDAC.