ABSTRACT Background 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. Methods 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. Results 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. Discussion 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.
Archibugi et al. (Thu,) studied this question.