Abstract
Purpose: Pancreatic ductal adenocarcinoma (PDAC) is lethal. It is projected that by 2030, PDAC will become the 2nd leading cause of cancer-related death. The intra-tumoural microbiome can influence pancreatic tumourigenesis and chemoresistance, and therefore patient survival. The role played by bile microbiota in PDAC is unknown. We aimed to define bile microbiome signatures in patients presenting with obstructive jaundice caused by benign and malignant pancreaticobiliary disease to develop novel cancer biomarkers.
Method: Prospective bile samples were obtained from 37 patients who underwent either endoscopic retrograde cholangiopancreatography (ERCP) or percutaneous transhepatic cholangiography (PTC). Variable regions (V3–V4) of the 16S rRNA genes were amplified by PCR and next generation sequencing was performed. The cohort consisted of 12 PDAC, 6 cholangiocarcinoma, 10 choledocholithiasis, 7 gallstone pancreatitis, and 2 primary sclerosing cholangitis patients. Bile samples from 8 patients were excluded from the analysis because of low read count.
Results: Using the 16S rRNA method, we identified a total of 108 genera from 29 individuals (12 PDAC and 17 benign). Bile microbial diversity significantly differed between patients with PDAC vs. benign disease (p=0.0173). The separation of PDAC from benign samples is clearly seen through unsupervised clustering based on Canberra distances shown in Figure 1. We found 4 genera to be of significantly different abundance between PDAC vs. benign groups by association p-value and supported by false discovery rate (fdr). These were Escherichia (p=6.5x10-6, fdr=0.0002), Rothia (p=0.011, fdr=0.074), Streptococcus (p=0.012, fdr=0.074) and Prevotella (p=0.015, fdr=0.079).
Conclusion: We show that patients with obstructive jaundice caused by PDAC have an altered microbiome composition in the bile, compared to those with benign disease. These bile-based microbes could be developed into potential diagnostic and prognostic biomarkers for PDAC and warrant further investigation.