Role of biliary stent and neoadjuvant chemotherapy in the pancreatic tumor microbiome

BACKGROUND: Intra-tumor microbiota have been implicated in pancreatic ductal adenocarcinoma (PDAC) development, treatment response and post-treatment survivorship. Moreover, therapeutic interventions targeting microbiota may improve the response to chemotherapy and immunotherapy, further emphasizing the critical need to understand the origins of and growth of bacteria within the pancreatic tumor microenvironment. Here, we studied the role of several clinical factors on the bacterial colonization of PDAC. RESULTS: We obtained matched tumor and normal pancreatic tissue specimens from 27 patients who had undergone surgical resection for PDAC between 2011 and 2015 from the University of Minnesota Biological Materials Procurement Network (BioNet). We found that 26 (48%) out of 54 pancreatic tissue samples harbored detectable bacterial communities using real-time PCR targeting the 16S rRNA gene. Bacterial colonization was detected significantly more frequently in samples from patients who had pancreatic head tumors, underwent Whipple procedure, or had preoperative biliary stent placement. There was also a significantly greater relative abundance of microbiota from the family Enterobacteriaceae among samples from patients who underwent biliary stent placement or neoadjuvant treatment with a combination of Gemcitabine and Paclitaxel. CONCLUSIONS: These findings suggest that biliary stent placement and neoadjuvant chemotherapy are associated with specific alterations that promote the infiltration and growth of intra-tumor bacteria in the setting of PDAC. Further studies exploring whether specific bacterial communities could contribute to increased chemoresistance will be essential for optimizing medical therapies in the future.