Cystic Pancreatic Lesion Bacteria Are Precursors to Pancreatic Cancer

Pancreatic cancer (PC) is one of the most aggressive and lethal types of cancer. The 5-year survival rate at the time of diagnosis is about 10%, as approximately 80%–85% of patients present either unresectable or metastatic disease. PC accounts for roughly 459,000 new cases and 432,000 deaths.

Cystic lesions, including intraductal papillary mucinous neoplasms (IPMNs), of the pancreas are common. Because they are known as precursors to pancreatic cancer, many patients need regular, lifelong check-ups, and a few can also require surgery. It would be valuable for the individual and for the healthcare to know more about the carcinogenic risk factors.

Medical Scientists at the Karolinska Institutet (Stockholm, Sweden) investigated the possibility to cultivate pancreatic microbiome from pancreatic cystic lesions associated with invasive cancer. Between February 2018 and November 2019, patients undergoing pancreatic surgery due to pancreatic cystic neoplasms (PCN) with cancer suspicion confirmed by radiological and clinical examinations participated in this study. Surgically removed pancreata were sampled for cyst fluid immediately upon resection in strict sterile conditions and cultured in aerobic and anaerobic blood culture bottles (BacT/ALERT 3D, bio-Merieux, Marcy l’Étoile, France). The culture-positive samples were streaked repetitively to obtain pure monocultures for a subsequent strain identification by MALDI-TOF MS profiling (MALDI-TOF MS Biotyper System (Bruker Daltonics, Bremen, Germany).

The investigators reported that 29 cases (24%) exhibited bacterial growth. Pancreas pathology revealed that all seven culture-positive cases had IPMN, of which five were in the high-grade dysplasia (HGD) stage or associated with invasive cancer (5/7; 71.4%). The culture-negative cases included only six malignant cases (6/21; 27.3%), the others were low-risk tumors such as IPMN-low grade dysplasia and serous cystic tumors (SCNs), and three cases also had signs of concomitant pancreatitis. MALDI-TOF MS profiling analysis shows Gammaproteobacteria and Bacilli dominate among individual bacteria isolates. Among cultivated bacteria, Gammaproteobacteria, particularly Klebsiella pneumoniae, but also Granulicatella adiacens and Enterococcus faecalis, demonstrate consistent pathogenic properties in pancreatic cell lines tested in ex vivo co-culture models.

Margaret Sällberg Chen, DDS, PhD, a Professor and senior author of the study said, “Some bacteria could cause double-stranded DNA breakage which is considered the first step of cellular lesion and cancer. We also found that antibiotics could prevent the damage to the DNA. Our findings not only confirm that bacteria play an important part in the development of cancer, they also illuminate new ways to attack the process.”

The authors concluded that their results showed an over-representation of Gammaproteobacteria and another class of bacterium called Bacilli. These bacteria reside normally in the digestive tract and have previously been shown to promote cancer drug resistance by interfering the effect of gemcitabine, a cytostatic drug used in pancreatic cancer treatment. The study showed that these bacteria were present in IPMNs and culturable in 24% of the cases. The study was published on November 24, 2021 in the journal Gut Microbes.


Related Links:
Karolinska Institutet
bio-Merieux
Bruker Daltonics