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

TLDR

Prospective cohort studies have linked oral diseases to an elevated risk of pancreatic cancer. This study aimed to assess salivary microbiota variations and their associations with pancreatic cancer and chronic pancreatitis. Researchers profiled salivary microbiota in 10 pancreatic cancer patients and 10 controls using a microarray, then identified and validated bacterial candidates by qPCR in an independent cohort of 28 cancer patients, 28 controls, and 27 chronic pancreatitis samples. Significant differences in salivary microflora were found, with 31 species increased and 25 decreased in cancer patients; two bacterial biomarkers (Neisseria elongata and Streptococcus mitis) achieved an AUC of 0.90, 96.4 % sensitivity, and 82.1 % specificity, supporting salivary microbiota as a non‑invasive biomarker source.

Abstract

<h3>Objective</h3> 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. <h3>Methods</h3> 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. <h3>Results</h3> 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 (<i>Neisseria elongata</i> and <i>Streptococcus mitis</i>) were validated using the independent samples, showing significant variation (p&lt;0.05, qPCR) between patients with pancreatic cancer and controls (n=56). Additionally, two bacteria (<i>Granulicatella adiacens</i> and <i>S mitis</i>) showed significant variation (p&lt;0.05, qPCR) between chronic pancreatitis samples and controls (n=55). The combination of two bacterial biomarkers (<i>N elongata</i> and <i>S mitis</i>) yielded a receiver operating characteristic plot area under the curve value of 0.90 (95% CI 0.78 to 0.96, p&lt;0.0001) with a 96.4% sensitivity and 82.1% specificity in distinguishing patients with pancreatic cancer from healthy subjects. <h3>Conclusions</h3> The authors observed associations between variations of patients9 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.