Oral administration of Enterococcus faecalis to mice induces acute and chronic inflammation in the pancreas: possible involvement in the pathophysiology of pancreatic diseases.

The poor prognosis of pancreatic cancer is partly due to a lack of knowledge about its etiology and high-risk groups. We have frequently observed latent chronic pancreatitis in tissue surrounding pancreatic cancer through pathological analysis alone. More recently, we found that Enterococcus faecalis was present at high frequency in the pancreatic juice of patients with pancreatic cancer. Therefore, we sought to understand whether E. faecalis causes pancreatitis, a risk factor for pancreatic cancer. In this study, we investigated the ability of orally administered E. faecalis to induce pancreatitis in a murine model, measuring inflammatory cytokine responses and performing histopathological analysis of pancreatic tissues including the detection of E. faecalis in the pancreas. We also checked the effect of pre-administration of a proton pump inhibitor on the induction of pancreatitis. Long-term oral administration of E. faecalis resulted in the development of pancreatitis as well as an increase in the expression of inflammatory cytokines. Short-term administration of fluorescently labeled E. faecalis allowed the visualization of the migration of the bacteria into the pancreas tissue, and pathological changes of acute inflammation were observed. Pretreatment with a proton pump inhibitor promoted the migration of E. faecalis to the pancreas. These results suggest that E. faecalis present in pancreatic juice could be one of the causes of latent chronic pancreatitis.