Variations of oral microbiota are associated with pancreatic diseases including pancreatic cancer
- James J Farrell1,
- Lei Zhang2,
- Hui Zhou2,
- David Chia3,
- David Elashoff4,
- David Akin2,
- Bruce J Paster5,
- Kaumudi Joshipura6,
- David T W Wong2,7,8,9
- 1Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California, USA
- 2UCLA School of Dentistry, Dental Research Institute, Los Angeles, California, USA
- 3Department of Pathology, David Geffen School of Medicine at UCLA, Los Angeles, California, USA
- 4Department of Biostatistics, UCLA School of Public Health, Los Angeles, California, USA
- 5Department of Molecular Genetics, The Forsyth Institute, Boston, Massachusetts, USA
- 6University of Puerto Rico, School of Dental Medicine, San Juan, Puerto Rico
- 7Jonsson Comprehensive Cancer Center, Los Angeles, California, USA
- 8Division of Head and Neck Surgery/Otolaryngology, David Geffen School of Medicine at UCLA, Los Angeles, California, USA
- 9Henry Samueli School of Engineering and Applied Science, David Geffen School of Medicine at UCLA, Los Angeles, California, USA
- Correspondence to Dr James J Farrell, UCLA David Geffen School of Medicine, Division of Digestive Diseases, 200 Med Plaza, Suite 365A, Los Angeles, CA 90095, USA;
Contributors LZ, JF and DW supervised all aspects of this study including study design, execution and data interpretation. LZ, JF and BP conducted the experiments and analysed experimental data. LZ, HZ, DE and BP contributed to data acquisition and data interpretation. JF provided human saliva samples. LZ, JF and KJ wrote the final manuscript. All authors reviewed the manuscript. James J Farrell and Lei Zhang: these authors contributed equally to this work.
- Accepted 21 July 2011
- Published Online First 12 October 2011
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.
- pancreatic cancer
- chronic pancreatitis
- gastrointestinal endoscopy
- gastrointestinal ultrasound
- pancreatic disease
- pancreatic disorders
- cancer prevention
- bacterial pathogenesis
- molecular genetics
- diabetes mellitus
- pancreatic cancer
- gastric cancer
- gastrointestinal cancer
- Helicobacter pylori
- acid-related diseases
- non-ulcer dyspepsia
- genetic polymorphisms
- gastric neoplasia
- gene expression
Funding Funding support was provided by the National Institute of Health (RO1DE017170 and R21CA126733).
Competing interests DTWW disclose ownership of intellectual property related to the saliva diagnostics field. The other authors disclosed no potential conflicts of interests.
Ethics approval UCLA IRB Committee. This study was approved by the UCLA Institutional Review Board.
Provenance and peer review Not commissioned; externally peer reviewed.