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.
Paired Duodenal and Salivary Microbiome Analysis in Pancreatic Cancer Without Duct Obstruction / Archibugi, L.; Bertoldi, L.; Benvenuto, G.; Sattin, E.; Ponz De Leon Pisani, R.; Fortunato, C.; Mariani, A.; Rossi, G.; Petrone, M. C.; Valle, G.; Reni, M.; Falconi, M.; Arcidiacono, P. G.; Capurso, G.. - In: UNITED EUROPEAN GASTROENTEROLOGY JOURNAL. - ISSN 2050-6406. - 14:2(2026). [10.1002/ueg2.70179]
Paired Duodenal and Salivary Microbiome Analysis in Pancreatic Cancer Without Duct Obstruction
Archibugi L.;Ponz De Leon Pisani R.;Fortunato C.;Rossi G.;Reni M.;Falconi M.;Arcidiacono P. G.;Capurso G.
2026-01-01
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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
