Myeloperoxidase gene knockout causes local inflammation and dysbiosis in the murine gut

Myeloperoxidase (MPO), predominantly expressed in neutrophils, catalyzes the production of hypochlorous acid (HOCl) that plays an integral role in the host defense against invading pathogens. However, little is known about its role in maintaining normal gut microbiome and function. Here, we report the comparisons of inflammation and microbiome in the intestines of WT and MPO^-/- mice. Immune cell profiling demonstrated that the MPO^-/- mice had significantly more neutrophils and T cells in their intestinal mucosae and significantly more fecal calprotectin as compared to the WT mice. Fluorescent dextran permeability of the bowel showed no difference between the two strains of mice. Carmine Red transit demonstrated that the MPO^-/- intestines had slower movements than did the WT controls. Sequencing the intestinal 16S rDNA of co-housed MPO^-/- and WT mice identified 13 bacterial families, 2 of which were unique to MPO^-/- and 7 to WT mice. Alpha diversity of the microbiome in WT intestines was significantly higher than that of MPO^-/- ones, and beta diversity of the two microbial communities of the two genotypes also differed significantly. Functional pathway analyses revealed distinct metabolic signatures. Thus, normal MPO function is important to intestinal health and its deficiency leads to gut inflammation and dysbiosis.