New Study Illuminates Bacteria’s Role in Pancreatic Cancer

New Study Illuminates Bacteria’s Role in Pancreatic Cancer
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Live bacteria from cystic pancreatic lesions, which are precursors to pancreatic cancer, have been found to have an over-representation of Gammaproteobacteria and Bacilli, both of which normally reside in the digestive tract. The study, which is led by researchers at Karolinska Institutet was  published in Gut Microbes and could lead to prophylactic interventions using local antibiotics, the authors say.

Pancreatic cancer is one of the most aggressive and deadly forms of cancer. Because it can have vague symptoms, if any, in its early stages, it is usually discovered late, by which time it has spread.

Consequently, at the time of diagnosis, the disease has become terminal in the majority of patients. But prevalence of the disease has increased, and pancreatic cancer is expected to soon pass breast cancer as the third most common cause of cancer-related death in the EU.

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.

Earlier studies from Karolinska Institutet and elsewhere showed the presence of oral bacteria in the pancreas might be a measure of IPMN lesion severity. The researchers at Karolinska Institutet have now built upon these preliminary results by using modern cultivation methods and proteomics to analyze the cystic fluid from 29 patients who underwent surgery for cystic pancreatic tumors between 2018 and 2019.

Their results showed and have previously been shown to promote cancer drug resistance by interfering with the effect of gemcitabine, a cytostatic drug used in pancreatic cancer treatment. The study showed that these bacteria were present in IPMNs and and could be cultured in 24 per cent of the cases.

On further study the researchers found that many of these bacteria could infect and even hide within the pancreatic cells, with harmful consequences.

“Some bacteria could cause double-stranded DNA breakage which is considered the first step of cellular lesion and cancer,” explains Margaret Sällberg Chen, professor at the Department of Dental Medicine at Karolinska Institutet. “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 question of how digestive tract bacteria enter the pancreas to then hide in its cells remains to be answered.

“Under normal circumstances, the duct from the intestines to the pancreas is closed, but in the presence of inflammation or injury, perhaps the bacteria may slip through,” says Volkan Özenci, senior consultant and associate professor at the Department of Laboratory Medicine, Karolinska Institutet. “The bacteria have likely migrated from the oral cavity and gastrointestinal tract to the pancreas through this duct. Some bacteria can also hide in human cells, such as white blood cells, and travel to the pancreas by the help of those cells.

The group says that their findings have potential clinical applications.

“It would, for instance, be relevant to be able to screen patients with IPMNs for this type of bacteria,” says the study’s co-first author Asif Halimi, a surgeon and doctoral student at the Department of Clinical Science, Intervention and Technology, Karolinska Institutet. “We’ve discussed the possibility of introducing a local antibiotic treatment in conjunction with, for example, an endoscopic examination or treatment. This would reduce the risk of bacterial infection and prevent future problems.”