Bacterial overgrowth in the cystic fibrosis transmembrane conductance regulator null mouse small intestine

Infection and Immunity
Oxana NorkinaRobert C De Lisle

Abstract

We recently reported the inflammation of the cystic fibrosis (CF) mouse small intestine, and we hypothesized bacterial overgrowth as a possible cause. Quantitative PCR of bacterial 16S genomic DNA in the CF mouse small intestine revealed an increase of greater than 40-fold compared to controls. Sequencing of 16S PCR products and Gram staining showed that the majority of bacteria in the CF mouse intestine were gram negative. Bacteria were observed to colonize the mucus that accumulates in the intestinal lumen of mice with CF. Impaired Paneth cell defenses were suggested by observation of partially dispersed Paneth granules in the mucus plugs of CF mouse intestinal crypts, and this mucus was strongly immunoreactive for Paneth cell bactericidal products. The role of bacterial overgrowth in intestinal inflammation in CF was tested by treating mice with oral antibiotics (ciprofloxacin and metronidazole) for 3 weeks, which reduced bacterial load in the CF mouse small intestine over 400-fold. Antibiotic treatment decreased the expression of the inflammation-related genes mast cell protease 2, leucine-rich alpha2 glycoprotein/leucine-rich high endothelial venule glycoprotein, suppressor of cytokine signaling 3, hematopoietic cell trans...Continue Reading

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