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Gut microbiome alterations in type 1 autoimmune pancreatitis after induction of remission by prednisolone
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  • Ken Kamata,
  • Tomohiro Watanabe,
  • Kosuke Minaga,
  • Akane Hara,
  • Ikue Sekai,
  • Yasuo Otsuka,
  • Tomoe Yoshikawa,
  • Ah-Mee Park,
  • Masatoshi Kudo
Ken Kamata
Kindai University Graduate School of Medical Sciences

Corresponding Author:ky11@leto.eonet.ne.jp

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Tomohiro Watanabe
Kindai University Graduate School of Medical Sciences
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Kosuke Minaga
Kindai University Graduate School of Medical Sciences
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Akane Hara
Kindai University Graduate School of Medical Sciences
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Ikue Sekai
Kindai University Graduate School of Medical Sciences
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Yasuo Otsuka
Kindai University Graduate School of Medical Sciences
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Tomoe Yoshikawa
Kindai University Graduate School of Medical Sciences
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Ah-Mee Park
Kindai University Graduate School of Medical Sciences
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Masatoshi Kudo
Kindai University Graduate School of Medical Sciences
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Abstract

Although increasing evidence demonstrates the association between intestinal dysbiosis and pancreatic diseases, such as chronic pancreatitis and pancreatic cancer, it remains largely unknown whether intestinal dysbiosis is involved in the immunopathogenesis of autoimmune pancreatitis (AIP). Recently, we found that intestinal dysbiosis mediates experimental AIP via the activation of plasmacytoid dendritic cells (pDCs), which can produce IFN-α and IL-33. However, candidate pathobionts for type 1 AIP have not been identified. In this study, we tried to identify pathobionts associated with type 1 AIP. Fecal samples were obtained from type 1 AIP patients before and after prednisolone (PSL) treatment and subjected to 16S ribosomal RNA sequencing to evaluate the composition of intestinal bacteria. Induction of remission by PSL was associated with the complete disappearance of Klebsiella species from feces, in two of the three analyzed patients with type 1 AIP. To assess the pathogenicity of Klebsiella species, mild experimental AIP was induced in MRL/MpJ mice by repeated injections of 10 μg of polyinosinic-polycytidylic acid (poly (I:C)) in combination with oral administration of heat-killed Klebsiella pneumoniae. The AIP pathology score was significantly higher in MRL/MpJ mice that received both oral administration of heat-killed K. pneumoniae and intraperitoneal injections of poly (I:C) than in those administered with either agent alone. Pancreatic accumulation of pDCs capable of producing large amounts of IFN-α and IL-33 was also significantly higher in mice that received both treatments. These data suggest that intestinal colonization by K. pneumoniae may play a pathogenic role in AIP.
25 May 2020Submitted to Clinical & Experimental Immunology
26 May 2020Submission Checks Completed
26 May 2020Assigned to Editor
26 May 2020Reviewer(s) Assigned
15 Jun 2020Review(s) Completed, Editorial Evaluation Pending
15 Jun 2020Editorial Decision: Revise Major
12 Aug 20201st Revision Received
12 Aug 2020Reviewer(s) Assigned
23 Aug 2020Review(s) Completed, Editorial Evaluation Pending
23 Aug 2020Editorial Decision: Accept
16 Nov 2020Published in Clinical and Experimental Immunology volume 202 issue 3 on pages 308-320. 10.1111/cei.13509