Survival mechanism of pancreatic tumor bacteria and their ability to metabolize chemotherapy drugs

Chemotherapy is a primary treatment for pancreatic cancer, and emerging evidence indicates that the gut microbiota can modulate its efficacy. While most studies have focused on gut-residing microbes, characterization of intra-tumoral microbes within the pancreas remains limited. Here, we report new insights into metabolic interactions between chemotherapeutic agents and patient-derived pancreatic tumor bacteria. These bacteria were isolated from intraductal papillary mucinous neoplasms (IPMNs), the main precursors to pancreatic cancer. Our findings demonstrate that patient-derived pancreatic tumor bacteria tolerate two commonly used chemotherapeutic drugs, 5-fluorouracil (5-FU) and gemcitabine, and can attenuate their cytotoxic effects on pancreatic cancer cells. Through whole-genome and transcriptomic analyses, we further reveal potential adaptation mechanisms that could enable these bacteria to persist in the tumor microenvironment and metabolize chemotherapeutics.