ALTERATIONS IN INTESTINAL PERMEABILITY CAUSE COLONIC INFLAMMATION AND FIBROSIS IN TYPE III PHOSPHATIDYLINOSITOL PHOSPHATE KINASE-DEFICIENT MICE

We recently established mice lacking the type III phosphatidylinositol phosphate kinase gene (PipkIII) in enterocytes, which represent a unique model of intestinal inflammation associated with extensive fibrosis that closely resembles human Crohn’s disease. These mutant mice develop spontaneous juvenile colitis with marked inflammatory cytokine expression, but the primary pathogenic mechanism remains unclear. In the present study, we found that administration of broad-specific antibiotics effectively ameliorated the colitis of PipkIII-deficient mice, suggesting the involvement of intestinal bacterial flora in the onset of colitis. Furthermore, we showed that altered intestinal permeability facilitating commensal bacteria entry putatively caused the intestinal inflammation and fibrosis observed in these mutant mice.