Paired Duodenal and Salivary Microbiome Analysis in Pancreatic Cancer Without Duct Obstruction

Bacterial migration from the oral cavity to the upper gastrointestinal tract has been proposed as a contributor to pancreatic ductal adenocarcinoma (PDAC) onset and prognosis. Whether PDAC is associated with alterations of the oral-duodenal microbiome continuum remains unclear.

In this prospective study, we profiled matched saliva and duodenal brushings from 24 treatment-naïve PDAC patients without ducts obstruction and 24 age- and sex-matched healthy controls (HC). Microbial composition was assessed by 16S rRNA gene sequencing. α-Diversity was evaluated using Faith's phylogenetic diversity (PD), observed ASVs, and Pielou's evenness; β-diversity using UniFrac, Bray-Curtis, and distance-based redundancy analysis (db-RDA). Associations with overall survival were examined using Cox models and ROC-derived cut-offs, with leave-one-out cross-validation for robustness.

Duodenal Faith's PD was significantly lower in PDAC than HC (q = 0.034), whereas richness and evenness did not differ; no α-diversity differences were observed in saliva. After adjustment for diabetes and periodontitis, lower duodenal Faith's PD (q = 0.048) and ASV richness (q = 0.030) in PDAC remained significant. β-Diversity was primarily driven by body site, but adjusted db-RDA revealed a small yet significant PDAC-HC difference in duodenal community composition (pseudo-F = 2.16, p = 0.002). Several genera showed differential abundance between groups. Higher salivary phylogenetic diversity predicted longer survival (aHR = 0.19, p = 0.001), along with specific genera associated with favourable prognosis.

PDAC is associated with reduced duodenal phylogenetic diversity and subtle disease-related shifts in duodenal microbiota, independent of major confounders and in the absence of duct obstruction. Both α-diversity and selected genera may hold prognostic relevance, supporting further validation in larger, stage-stratified cohorts.