Variations of oral microbiota are associated with pancreatic diseases including pancreatic cancer

• Published in: Gut Vol. 61; no. 4; pp. 582 - 588
• Main Authors: Farrell, James J, Zhang, Lei, Zhou, Hui, Chia, David, Elashoff, David, Akin, David, Paster, Bruce J, Joshipura, Kaumudi, Wong, David T W
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group Ltd and British Society of Gastroenterology 01.04.2012; BMJ Publishing Group; BMJ Publishing Group LTD
• Subjects: acid-related diseases; Aged; Aged, 80 and over; Bacteria; Bacteria - classification; Bacteria - isolation & purification; bacterial pathogenesis; Bacterial Typing Techniques; Biological and medical sciences; biomarker; Biomarkers; Biomarkers - metabolism; biostatistics; cancer; cancer prevention; Cancer therapies; Case-Control Studies; Chronic illnesses; chronic pancreatitis; Diabetes; diabetes mellitus; Disease; endoscopy; Ethnicity; Female; gastric cancer; gastric neoplasia; Gastroenterology. Liver. Pancreas. Abdomen; gastrointestinal cancer; gastrointestinal endoscopy; gastrointestinal ultrasound; gene expression; genetic polymorphisms; Granulicatella adiacens; Helicobacter pylori; Humans; Inflammation; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Lung cancer; Male; Medical sciences; Metagenome; microbiota; Middle Aged; molecular genetics; Neisseria elongata; non-ulcer dyspepsia; Pancreatic cancer; pancreatic disease; Pancreatic Diseases - microbiology; pancreatic disorders; Pancreatic Neoplasms - microbiology; pancreatitis; Pancreatitis, Chronic - microbiology; Pathogenesis; Phylogeny; Real-Time Polymerase Chain Reaction - methods; Risk factors; RNA, Bacterial - genetics; RNA, Ribosomal, 16S - genetics; Rodents; Saliva; Saliva - microbiology; Sensitivity and Specificity; Smoking; Streptococcus mitis; Studies; Tumors; Pancreas cancer; Gastroenterology; Oral administration; Digestive diseases; Malignant tumor; Cancer; Pancreatic disease
• ISSN: 0017-5749; 1468-3288; 1468-3288
• DOI: 10.1136/gutjnl-2011-300784

ObjectiveThe associations between oral diseases and increased risk of pancreatic cancer have been reported in several prospective cohort studies. In this study, we measured variations of salivary microbiota and evaluated their potential associations with pancreatic cancer and chronic pancreatitis.MethodsThis study was divided into three phases: (1) microbial profiling using the Human Oral Microbe Identification Microarray to investigate salivary microbiota variation between 10 resectable patients with pancreatic cancer and 10 matched healthy controls, (2) identification and verification of bacterial candidates by real-time quantitative PCR (qPCR) and (3) validation of bacterial candidates by qPCR on an independent cohort of 28 resectable pancreatic cancer, 28 matched healthy control and 27 chronic pancreatitis samples.ResultsComprehensive comparison of the salivary microbiota between patients with pancreatic cancer and healthy control subjects revealed a significant variation of salivary microflora. Thirty-one bacterial species/clusters were increased in the saliva of patients with pancreatic cancer (n=10) in comparison to those of the healthy controls (n=10), whereas 25 bacterial species/clusters were decreased. Two out of six bacterial candidates (Neisseria elongata and Streptococcus mitis) were validated using the independent samples, showing significant variation (p<0.05, qPCR) between patients with pancreatic cancer and controls (n=56). Additionally, two bacteria (Granulicatella adiacens and S mitis) showed significant variation (p<0.05, qPCR) between chronic pancreatitis samples and controls (n=55). The combination of two bacterial biomarkers (N elongata and S mitis) yielded a receiver operating characteristic plot area under the curve value of 0.90 (95% CI 0.78 to 0.96, p<0.0001) with a 96.4% sensitivity and 82.1% specificity in distinguishing patients with pancreatic cancer from healthy subjects.ConclusionsThe authors observed associations between variations of patients' salivary microbiota with pancreatic cancer and chronic pancreatitis. This report also provides proof of salivary microbiota as an informative source for discovering non-invasive biomarkers of systemic diseases.