Merali, Nabeel, Chouari, Tarak, Terroire, Julien, Jessel, Maria-Danae 
ORCID: 0009-0002-2999-9914, Liu, Daniel SK, Smith, James-Halle, Wooldridge, Tyler, Dhillon, Tony, Jiménez, José I, Krell, Jonathan et al (show 8 more authors)
(2023)
Bile Microbiome Signatures Associated with Pancreatic Ductal Adenocarcinoma Compared to Benign Disease: A UK Pilot Study.
International journal of molecular sciences, 24 (23).
p. 16888.
Abstract
Pancreatic ductal adenocarcinoma (PDAC) has a very poor survival. 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 that can effectively distinguish malignant from benign tumours in patients presenting with obstructive jaundice caused by benign and malignant pancreaticobiliary disease. Prospective bile samples were obtained from 31 patients who underwent either Endoscopic Retrograde Cholangiopancreatography (ERCP) or Percutaneous Transhepatic Cholangiogram (PTC). Variable regions (V3-V4) of the 16S rRNA genes of microorganisms present in the samples were amplified by Polymerase Chain Reaction (PCR) and sequenced. The cohort consisted of 12 PDAC, 10 choledocholithiasis, seven gallstone pancreatitis and two primary sclerosing cholangitis patients. Using the 16S rRNA method, we identified a total of 135 genera from 29 individuals (12 PDAC and 17 benign). The bile microbial beta diversity significantly differed between patients with PDAC vs. benign disease (Permanova <i>p</i> = 0.0173). The separation of PDAC from benign samples is clearly seen through unsupervised clustering of Aitchison distance. We found three genera to be of significantly lower abundance among PDAC samples vs. benign, adjusting for false discovery rate (FDR). These were <i>Escherichia</i> (FDR = 0.002) and two unclassified genera, one from <i>Proteobacteria</i> (FDR = 0.002) and one from <i>Enterobacteriaceae</i> (FDR = 0.011). In the same samples, the genus <i>Streptococcus</i> (FDR = 0.033) was found to be of increased abundance in the PDAC group. 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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | Bile, Humans, Carcinoma, Pancreatic Ductal, Pancreatic Neoplasms, Jaundice, Obstructive, RNA, Ribosomal, 16S, Prospective Studies, Pilot Projects, Microbiota, United Kingdom |
| Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 26 Mar 2024 10:14 |
| Last Modified: | 26 Mar 2024 15:29 |
| DOI: | 10.3390/ijms242316888 |
| Open Access URL: | https://doi.org/10.3390/ijms242316888 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3179937 |
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