Gut microbiome alterations in type 1 autoimmune pancreatitis after
induction of remission by prednisolone
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.