Gut Microbiome Compositional and Functional Signatures Associated with Chemotherapy Response in Pancreatic Ductal Adenocarcinoma: An Exploratory Cohort Study.
7 affiliations
- 1HPB Unit, General Surgery Department, Pederzoli Hospital, Peschiera del Garda, 37019 Verona, Italy.
- 2PhD School of Applied Medical-Surgical Sciences, University of Rome Tor Vergata, 00133 Rome, Italy.
- 3Wellmicro Srl, 40138 Bologna, Italy.
- 4Clinical Biochemistry Section, Department of Engineering for Innovation Medicine, University of Verona, 37129 Verona, Italy.
- 5Department of Biochemistry, Pederzoli Hospital, Peschiera del Garda, 37019 Verona, Italy.
- 6Collegium Medicum, Spoleczna Akademia Nauk University, 90-113 Łódź, Poland.
- 7Section of Clinical Nutrition and Nutrigenomic, Department of Biomedicine and Prevention, University of Rome Tor Vergata, 00133 Rome, Italy.
Abstract
Background/Objectives: The gut microbiome modulates chemotherapy efficacy in pancreatic ductal adenocarcinoma (PDAC), yet its relationship with the clinically relevant endpoint of post-chemotherapy surgical eligibility remains poorly characterised. We explored whether baseline gut microbiome composition and metagenomically predicted metabolic function differ between chemotherapy responders and non-responders in PDAC. Methods: In this prospective single-centre exploratory cohort study, faecal samples were collected from 15 patients with non-immediately resectable PDAC at diagnosis, before chemotherapy. Whole-genome shotgun metagenomics was performed, and microbial functional capacity was inferred through an assembly-based pipeline. Patients were classified as responders (achieved surgical eligibility, n = 6) or non-responders (n = 9). Results: At baseline, responders showed enrichment of Collinsella aerofaciens (p = 0.026) and Butyrivibrio fibrisolvens (p = 0.012), while non-responders were enriched in oral-origin bacteria (Streptococcus gordonii, Actinomyces spp., Rothia dentocariosa). Predicted butyrate showed the largest effect size difference between groups but did not reach significance (p = 0.179); responders also had broadly elevated predicted SCFAs and bile acids. However, chemotherapy regimen (mFOLFIRINOX in 5/6 responders vs. 2/9 non-responders; Fisher p = 0.041) and disease stage were unevenly distributed between groups. Conclusions: This exploratory study identifies the compositional and functional microbiome features distinguishing PDAC chemotherapy responders from non-responders. These associations are confounded by disease stage and regimen and require validation in larger, regimen-stratified cohorts before predictive or mechanistic claims can be made.
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BibTeX
@article{pizzocaro2026microbiome,
title = {{Gut Microbiome Compositional and Functional Signatures Associated with Chemotherapy Response in Pancreatic Ductal Adenocarcinoma: An Exploratory Cohort Study.}},
author = {Erica Pizzocaro and Matteo Soverini and Gian Luca Salvagno and Ashkan Lotfollahzadeh and Barbara Santacroce and Giulia Bruno and Isabella Frigerio and Laura Di Renzo and Andrea Castagnetti and Giovanni Butturini},
journal = {Metabolites},
year = {2026},
month = sep,
doi = {10.3390/metabo16100720},
url = {https://europepmc.org/article/MED/42941196},
note = {CC BY},
}
RIS
TY - JOUR
TI - Gut Microbiome Compositional and Functional Signatures Associated with Chemotherapy Response in Pancreatic Ductal Adenocarcinoma: An Exploratory Cohort Study.
AU - Erica Pizzocaro
AU - Matteo Soverini
AU - Gian Luca Salvagno
AU - Ashkan Lotfollahzadeh
AU - Barbara Santacroce
AU - Giulia Bruno
AU - Isabella Frigerio
AU - Laura Di Renzo
AU - Andrea Castagnetti
AU - Giovanni Butturini
PY - 2026
DA - 2026/09/28
JO - Metabolites
DO - 10.3390/metabo16100720
UR - https://europepmc.org/article/MED/42941196
AB - Background/Objectives: The gut microbiome modulates chemotherapy efficacy in pancreatic ductal adenocarcinoma (PDAC), yet its relationship with the clinically relevant endpoint of post-chemotherapy surgical eligibility remains poorly characterised. We explored whether baseline gut microbiome composition and metagenomically predicted metabolic function differ between chemotherapy responders and non-responders in PDAC. Methods: In this prospective single-centre exploratory cohort study, faecal samples were collected from 15 patients with non-immediately resectable PDAC at diagnosis, before chemotherapy. Whole-genome shotgun metagenomics was performed, and microbial functional capacity was inferred through an assembly-based pipeline. Patients were classified as responders (achieved surgical eligibility, n = 6) or non-responders (n = 9). Results: At baseline, responders showed enrichment of Collinsella aerofaciens (p = 0.026) and Butyrivibrio fibrisolvens (p = 0.012), while non-responders were enriched in oral-origin bacteria (Streptococcus gordonii, Actinomyces spp., Rothia dentocariosa). Predicted butyrate showed the largest effect size difference between groups but did not reach significance (p = 0.179); responders also had broadly elevated predicted SCFAs and bile acids. However, chemotherapy regimen (mFOLFIRINOX in 5/6 responders vs. 2/9 non-responders; Fisher p = 0.041) and disease stage were unevenly distributed between groups. Conclusions: This exploratory study identifies the compositional and functional microbiome features distinguishing PDAC chemotherapy responders from non-responders. These associations are confounded by disease stage and regimen and require validation in larger, regimen-stratified cohorts before predictive or mechanistic claims can be made.
SN - 2218-1989
ER -