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, with salivary α-diversity and selected genera holding prognostic relevance.
Key Findings
Results
Duodenal Faith's phylogenetic diversity was significantly lower in PDAC patients compared to healthy controls.
Study included 24 treatment-naïve PDAC patients without duct obstruction and 24 age- and sex-matched healthy controls
Duodenal Faith's PD was significantly lower in PDAC than HC (q = 0.034)
After adjustment for diabetes and periodontitis, lower duodenal Faith's PD remained significant (q = 0.048)
Adjusted lower duodenal ASV richness also remained significant after confounders (q = 0.030)
Richness and evenness did not differ between groups in unadjusted analysis
Results
No α-diversity differences were observed in saliva between PDAC patients and healthy controls.
α-Diversity was evaluated using Faith's phylogenetic diversity (PD), observed ASVs, and Pielou's evenness
While duodenal α-diversity differed, salivary α-diversity measures showed no significant difference between PDAC and HC
Microbial composition was assessed by 16S rRNA gene sequencing
Matched saliva and duodenal brushings were profiled from the same participants
Results
β-Diversity was primarily driven by body site, but adjusted analysis revealed a significant PDAC-related difference in duodenal community composition.
β-diversity was assessed using UniFrac, Bray-Curtis, and distance-based redundancy analysis (db-RDA)
Adjusted db-RDA revealed a small yet significant PDAC-HC difference in duodenal community composition (pseudo-F = 2.16, p = 0.002)
The primary driver of β-diversity differences was body site (saliva vs. duodenum) rather than disease status
Results
Higher salivary phylogenetic diversity was associated with longer overall survival in PDAC patients.
Associations with overall survival were examined using Cox models and ROC-derived cut-offs
Leave-one-out cross-validation was used for robustness
Specific genera were also associated with favourable prognosis
Results
Several genera showed differential abundance between PDAC patients and healthy controls.
Differential abundance analysis was performed between PDAC and HC groups
The paper reports differential abundance in both duodenal and salivary microbiomes
Specific genera associated with favourable prognosis were identified in the salivary microbiome
Analyses were conducted on matched paired samples from each participant
Methods
The study was designed to examine the oral-duodenal microbiome continuum in PDAC specifically in the absence of duct obstruction to minimize confounding from biliary or pancreatic obstruction.
All 24 PDAC patients were treatment-naïve and without duct obstruction
Bacterial migration from the oral cavity to the upper gastrointestinal tract has been proposed as a contributor to PDAC onset and prognosis
Matched saliva and duodenal brushings were collected prospectively
Controls were age- and sex-matched healthy individuals (n = 24)
Archibugi L, Bertoldi L, Benvenuto G, Sattin E, Ponz De Leon Pisani R, Fortunato C, et al.. (2026). Paired Duodenal and Salivary Microbiome Analysis in Pancreatic Cancer Without Duct Obstruction.. United European gastroenterology journal. https://doi.org/10.1002/ueg2.70179