Association between gut microbiome and treatment outcomes in metastatic pancreatic cancer patients: A pilot study.

Abstract

e16381 Background: Pancreatic ductal adenocarcinoma (PDAC) remains a leading cause of cancer mortality in Japan, currently ranking fourth. While gemcitabine plus nab-paclitaxel is a standard first-line regimen for metastatic PDAC, substantial inter-patient variability in treatment response is observed. Emerging evidence suggests that the gut microbiome may modulate chemotherapy efficacy. This pilot study aimed to explore the association between gut microbiome profiles and clinical outcomes in Japanese patients with metastatic PDAC. Methods: This retrospective pilot study enrolled patients with metastatic PDAC treated with first-line palliative chemotherapy between July 2021 and August 2023 (N = 19). Baseline fecal samples were collected prior to treatment initiation. Microbial DNA was extracted and 16S rRNA sequencing was performed. Bioinformatic analysis was conducted using QIIME2. Alpha diversity indices and taxonomic composition were analyzed. Clinical response was assessed according to RECIST v1.1. Exploratory analyses were performed to examine associations between microbial metrics and outcomes, including response rate and overall survival (OS), using Wilcoxon rank-sum test, Fisher’s exact test, and Kaplan–Meier analysis. Results: Of the 19 patients, 10 were classified as responders (PR or SD) and 9 as non-responders (PD). No statistically significant differences were observed in alpha diversity between responders and non-responders (e.g. Chao1, p = 0.624; Shannon index, p = 0.838; Faith’s PD, p = 0.437). Descriptive taxonomic analysis showed a relative enrichment of Streptococcus in non-responders. Median OS did not differ significantly between high vs. low Chao1 groups (12.2 vs. 15.7 months, p = 0.164) nor high Shannon vs. low Shannon groups (12.2 vs. 15.5 months, p = 0.219). Exploratory univariate analyses suggested potential associations between clinical factors such as diabetes status and baseline CA19-9 levels with outcomes, although these findings were not statistically robust. Conclusions: This pilot study did not identify a clear association between baseline gut microbiome diversity and chemotherapy outcomes in Japanese patients with metastatic PDAC. A descriptive trend toward increased Streptococcus abundance in non-responders was observed, consistent with prior observational studies linking this genus to adverse outcomes in gastrointestinal malignancies. However, given the limited sample size, this study was statistically underpowered to detect subtle microbial effects. Larger, prospective longitudinal studies are required to validate these microbial associations in PDAC.