Abstract 6515: Candida -associated microbiome in pancreatic ductal adenocarcinoma

Carlos H.F. Chan; Casandro J. Chan; Ashutosh K. Mangalam; Po Hien Ear

doi:10.1158/1538-7445.AM2025-6515

Candida species are commonly found in bile collected during surgery in pancreatic ductal adenocarcinoma (PDAC) patients. We have previously shown that bile and tumor-associated Candida albicans are associated with higher pathological stage, worse pathological response to neoadjuvant chemotherapy, worse overall survival, and epithelial-mesenchymal transition gene signature. Here we investigated the association between Candida species and other commonly found bacterial species in the biliary system of PDAC patients with biliary stents. Patients undergoing pancreatectomy with available intraoperative bile cultures (aerobic, anaerobic and fungal) were identified in a prospective single-institution cohort. 16S rRNA and ITS sequencing was performed using available frozen banked bile samples from these patients. Relative abundance (RA) was determined as the ratio of an individual microbial count over the total microbial count in a given sample. Bile acid contents in these bile samples were determined using LC-MS methods. Of 135 patients with preoperative biliary stenting, the most commonly found bacteria were Enterococcus (56%), Streptococcus (47%), Klebsiella (47%), Enterobacter (26%), Escherichia (25%), Prevotella (22%), and Clostridioides (15%). Candida species were found in 36% of these patients. 76% of patients without preoperative biliary stenting had negative bacterial cultures. Using 16S rRNA and ITS sequencing data (N=27), the presence of Candida (RA > 0) was significantly associated with the presence of Enterococcus species (RA of 24.8% in Candida+ samples vs. 7.8% in Candida- samples, P=0.046). Enterococcus was also found to be associated with more unconjugated bile acids in the bile samples (unconjugated/conjugated bile acid ratios: cholic acid, 3.07 vs. 0.30, P=0.089; deoxycholic acid, 3.57 vs. 0.39, P=0.029; chenodeoxycholic acid, 2.54 vs. 0.35, P=0.045). Our data show Candida and Enterococcus species frequently co-exist in the biliary system of PDAC patients with biliary stents and that Enterococcus species may be responsible for bile acid deconjugation within the biliary system. Whether Enterococcus species and unconjugated bile acids promote the colonization and survival of Candida within the biliary system remains to be determined in future investigation.

Abstract 6515: Candida -associated microbiome in pancreatic ductal adenocarcinoma

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