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Biochem Biophys Res Commun. 2018 Nov 3. pii: S0006-291X(18)32357-X. doi: 10.1016/j.bbrc.2018.10.169. [Epub ahead of print]

Possible involvement of Enterococcus infection in the pathogenesis of chronic pancreatitis and cancer.

Author information

1
Department of Molecular Biochemistry and Clinical Investigation, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
2
aMs New Otani Clinic, Osaka, Osaka, Japan.
3
Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
4
Department of Gastroenterological Surgery, Kansai-Rosai Hospital, Amagasaki, Hyogo, Japan.
5
Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Gifu, Japan.
6
Department of Gastroenterology and Hepatology, Japan Community Health Care Organization Osaka Hospital, Osaka, Osaka, Japan.
7
Department of Gastroenterological Surgery, Osaka Police Hospital, Osaka, Osaka, Japan.
8
Cosmos Corp. Fujimoto Eye Clinic, Osaka, Osaka, Japan.
9
Department of Pathology, International University of Health and Welfare, Narita, Chiba, Japan.
10
Department of Molecular Medical Microbiology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
11
Department of Molecular Biochemistry and Clinical Investigation, Osaka University Graduate School of Medicine, Suita, Osaka, Japan. Electronic address: emiyoshi@sahs.med.osaka-u.ac.jp.

Abstract

(Aim) Bacterial infection underlies the pathogenesis of many human diseases, including acute and chronic inflammation. Here, we investigated a possible role for bacterial infection in the progression of chronic pancreatitis. (Materials and Methods) Pancreatic juice was obtained from patients with pancreatic cancer (n = 20) or duodenal cancer/bile duct cancer (n = 16) and subjected to PCR using universal primers for the bacterial 16S ribosomal RNA gene. Bacterial species were identified by PCR using bile samples from four pancreatic cancer patients. PCR products were subcloned into T-vectors, and the sequences were then analyzed. Immunohistochemical and serologic analyses for Enterococcus faecalis infection were performed on a large cohort of healthy volunteers and patients with chronic pancreatitis or pancreatic cancer and on mice with caerulein-induced chronic pancreatitis. The effect of E. faecalis antigens on cytokine secretion by pancreatic cancer cells was also investigated. (Results) We found that 29 of 36 pancreatic juice samples were positive for bacterial DNA. Enterococcus and Enterobacter species were detected primarily in bile, which is thought to be a pathway for bacterial infection of the pancreas. Enterococcus faecalis was also detected in pancreatic tissue from chronic pancreatitis and pancreatic cancer patients; antibodies to E. faecalis capsular polysaccharide were elevated in serum from chronic pancreatitis patients. Enterococcus-specific antibodies and pancreatic tissue-associated E. faecalis were detected in mice with caerulein-induced chronic pancreatitis. Addition of Enterococcus lipoteichoic acid and heat-killed bacteria induced expression of pro-fibrotic cytokines by pancreatic cancer cells in vitro. (Conclusion) Infection with E. faecalis may be involved in chronic pancreatitis progression, ultimately leading to development of pancreatic cancer.

KEYWORDS:

Chronic pancreatitis; Enterococcus faecalis; Pancreatic cancer

PMID:
30401562
DOI:
10.1016/j.bbrc.2018.10.169

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