CHANGES OF ORAL AND DUODENAL MICROBIOTA IN PATIENTS WITH PANCREATIC CANCER ARE POSSIBLE DIAGNOSTIC AND PROGNOSTIC BIOMARKERS

Aims Microbiome is associated with pancreatic cancer(PDAC) risk/survival. It was hypothesized that bacteria migrate from the mouth through duodenum into the pancreas with a protumorigenic effect. Changes of duodenal microbiome of head PDAC were reported, but may be due to impaired exocrine function and bile flow.Also, such studies were underpowered and oral/duodenal microbiome were not compared.We aimed to assess oral/duodenal microbiome in a PDAC cohort undergoing EUS,with lesions not obstructing(PDAC-NO) biliopancreatic ducts and matched healthy controls(HC), and investigate signatures predicting survival.

Methods A sample-size calculation was performed enrolling 10 patients. PDAC and sex/age-matched HC were enrolled during EUS, performing saliva collection and duodenal brushing. Bacterial 16S-RNA gene was extracted, amplified and underwent NGS. Results were analyzed through Qiime2 with comparison of alpha and beta-diversity, and differential abundances. Survival analyses were performed.

Results 96 samples were collected from 24PDAC-NO/24HC. Technical success was 97.9%. There was a significantly reduced Alpha-diversity (OTUs and Faith-PD) in PDAC-NO brushing compared to HC(p=0.04), as also to PDAC-NO saliva(p=0.01). There was a significant Beta-diversity difference between brushing and saliva of PDAC-NO(q-value=0.025). The most abundant bacterium in PDAC-NO duodenum was P.Aggregatibacter. A lower alpha-diversity as also the presence of specific species were associated to a reduced/increased survival.

Conclusions The use of brushing for duodenal microbiome evaluation is feasible and fast. Even in absence of ducts obstruction, PDAC patients have lower alpha-diversity in the duodenum compared to HC, as also in PDAC, the duodenum has lower alpha-diversity than in the saliva. A specific microbiome signature and a lower alpha-diversity predict survival in PDAC.

Publication History

Article published online:
14 April 2022