Bile Microbiome Signatures Associated with Pancreatic Ductal Adenocarcinoma Compared to Benign Disease: A UK Pilot Study.

Autor: Merali N; Minimal Access Therapy Training Unit (MATTU), Royal Surrey County Hospital NHS Foundation Trust, Egerton Road, Guildford GU2 7XX, UK.; Department of Hepato-Pancreato-Biliary (HPB) Surgery, Royal Surrey County Hospital NHS Foundation Trust, Egerton Road, Guildford GU2 7XX, UK.; Section of Oncology, Department of Clinical and Experimental Medicine, Faculty of Health and Medical Science, University of Surrey, Guildford GU2 7WG, UK., Chouari T; Department of Hepato-Pancreato-Biliary (HPB) Surgery, Royal Surrey County Hospital NHS Foundation Trust, Egerton Road, Guildford GU2 7XX, UK.; Section of Oncology, Department of Clinical and Experimental Medicine, Faculty of Health and Medical Science, University of Surrey, Guildford GU2 7WG, UK., Terroire J; Surrey Institute for People-Centred AI, University of Surrey, Guildford GU2 7XH, UK.; Section of Statistical Multi-Omics, Department of Clinical and Experimental Medicine, Faculty of Health and Medical Science, University of Surrey, Guildford GU2 7WG, UK., Jessel MD; Section of Oncology, Department of Clinical and Experimental Medicine, Faculty of Health and Medical Science, University of Surrey, Guildford GU2 7WG, UK., Liu DSK; Division of Cancer, Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital Campus, London W12 0NN, UK., Smith JH; Hepatobiliary and Pancreatic Surgery Unit, Queen Elizabeth Hospital Birmingham, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TH, UK., Wooldridge T; Section of Oncology, Department of Clinical and Experimental Medicine, Faculty of Health and Medical Science, University of Surrey, Guildford GU2 7WG, UK., Dhillon T; Section of Oncology, Department of Clinical and Experimental Medicine, Faculty of Health and Medical Science, University of Surrey, Guildford GU2 7WG, UK., Jiménez JI; Department of Life Sciences, Imperial College London, London SW7 2AZ, UK., Krell J; Division of Cancer, Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital Campus, London W12 0NN, UK., Roberts KJ; Hepatobiliary and Pancreatic Surgery Unit, Queen Elizabeth Hospital Birmingham, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TH, UK., Rockall TA; Minimal Access Therapy Training Unit (MATTU), Royal Surrey County Hospital NHS Foundation Trust, Egerton Road, Guildford GU2 7XX, UK., Velliou E; Centre for 3D Models of Health and Disease, Division of Surgery and Interventional Science, University College London (UCL), London W1W 7TY, UK., Sivakumar S; Oncology Department, Institute of Immunology and Immunotherapy, Birmingham Medical School, University of Birmingham, Birmingham B15 2TT, UK., Giovannetti E; Department of Medical Oncology, VU University Medical Center, Cancer Center Amsterdam, 1081 HV Amsterdam, The Netherlands.; Cancer Pharmacology Lab, AIRC Start Up Unit, Fondazione Pisana per la Scienza, San Giuliano Terme PI, 56017 Pisa, Italy., Demirkan A; Surrey Institute for People-Centred AI, University of Surrey, Guildford GU2 7XH, UK.; Section of Statistical Multi-Omics, Department of Clinical and Experimental Medicine, Faculty of Health and Medical Science, University of Surrey, Guildford GU2 7WG, UK., Annels NE; Section of Oncology, Department of Clinical and Experimental Medicine, Faculty of Health and Medical Science, University of Surrey, Guildford GU2 7WG, UK., Frampton AE; Minimal Access Therapy Training Unit (MATTU), Royal Surrey County Hospital NHS Foundation Trust, Egerton Road, Guildford GU2 7XX, UK.; Department of Hepato-Pancreato-Biliary (HPB) Surgery, Royal Surrey County Hospital NHS Foundation Trust, Egerton Road, Guildford GU2 7XX, UK.; Section of Oncology, Department of Clinical and Experimental Medicine, Faculty of Health and Medical Science, University of Surrey, Guildford GU2 7WG, UK.; Division of Cancer, Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital Campus, London W12 0NN, UK.
Jazyk: angličtina
Zdroj: International journal of molecular sciences [Int J Mol Sci] 2023 Nov 28; Vol. 24 (23). Date of Electronic Publication: 2023 Nov 28.
DOI: 10.3390/ijms242316888
Abstrakt: 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 p = 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 Escherichia (FDR = 0.002) and two unclassified genera, one from Proteobacteria (FDR = 0.002) and one from Enterobacteriaceae (FDR = 0.011). In the same samples, the genus Streptococcus (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.
Databáze: MEDLINE
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