Klebsiella pneumoniae increases the risk of inflammation and colitis in a murine model of intestinal bowel disease.

Intrarectal treatment with 2,4,6-trinitrobenzene sulfonic acid (TNBS), an inducer of intestinal inflammation, in mice increases the population size of Enterobacteriaceae, particularly Klebsiella pneumoniae, while reducing the population size of lactic acid bacteria. Therefore, we investigated the effects of these bacteria in TNBS-induced colitis in mice. Colitis was induced in vivo by rectal administration of TNBS in male Institute of Cancer Research mice. Inflammatory markers were determined by enzyme-linked immunosorbent assay and immunoblot analysis. Oral administration of K. pneumoniae increased COX-2, IL-1β, IL-6 and TNF-α expression, NF-κB activation, and lipid peroxidation in the colon, but reduced tight junction-associated proteins, claudin-1, ZO-1 and occludin. K. pneumoniae also deteriorated the expression of inflammatory markers and tight junction-associated proteins in TNBS-induced colitic mice. K. pneumoniae produced β-glucuronidase and lipopolysaccharide, which potently induced NO and COX-2 production in murine peritoneal macrophages. However, oral administration of Lactobacillus johnsonii, which is isolated from the feces of mice, inhibited TNBS-induced colon shortening, the reduction of tight junction-associated proteins, expression of inflammatory markers, and lipid peroxidation. These findings suggest that the disturbance of intestinal bacterial composition, and in particular the irregular increase of K. pneumoniae in the colon, may cause colitis.