title: Variations of oral microbiota are associated with pancreatic diseases including pancreatic cancer.
abstract: OBJECTIVE
  The 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.
  
  
  METHODS
  This 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.
  
  
  RESULTS
  Comprehensive 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.
  
  
  CONCLUSIONS
  The 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.
authors: Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA. jfarrell@mednet.ucla.edu
authors: James J
authors: JJ
authors: Farrell
authors: Lei
authors: L
authors: Zhang
authors: Hui
authors: H
authors: Zhou
authors: David
authors: D
authors: Chia
authors: David
authors: D
authors: Elashoff
authors: David
authors: D
authors: Akin
authors: Bruce J
authors: BJ
authors: Paster
authors: Kaumudi
authors: K
authors: Joshipura
authors: David T W
authors: DT
authors: Wong
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001419:Bacteria / Q000145:classification / Q000302:isolation & purification*; D015373:Bacterial Typing Techniques; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008297:Male; D054892:Metagenome; D008875:Middle Aged; D010182:Pancreatic Diseases / Q000382:microbiology*; D010190:Pancreatic Neoplasms / Q000382:microbiology*; D050500:Pancreatitis, Chronic / Q000382:microbiology; D010802:Phylogeny; D012329:RNA, Bacterial / Q000235:genetics; D012336:RNA, Ribosomal, 16S / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods; D012463:Saliva / Q000382:microbiology*; D012680:Sensitivity and Specificity
chemical_list: D015415:Biomarkers; D012329:RNA, Bacterial; D012336:RNA, Ribosomal, 16S