Myeloperoxidase loss of function leads to intestinal inflammation and dysbiosis 4033

Abstract Description Myeloperoxidase (MPO) is a unique peroxidase, predominantly expressed in neutrophils and catalyzing two electron oxidation of chloride (Cl–) to produce hypochlorous acid (HOCl), a potent microbicidal oxidant. The MPO-Cl–-HOCl system constitutes an integral part of the host immune defense against invading pathogens. However, little is known about how this system influences normal microflora and organ function. Here we investigated how MPO affects intestinal microbiota, inflammation and transit. Microbial DNAs from MPO-/- and wild-type (WT) mouse intestines were subjected to 16S ribosomal DNA sequencing. Results show that Peptostreptococcaceae and Erysipelatoclostridiaceae were unique to MPO-/- mice, while Ruminococcaceae, Desulfovibrionaceae, and Bifidobacteriaceae to WT mice. Shannon Entropy, Observed Features, and Faith PD of the WT samples were significantly higher than those of the MPO-/- samples. There were significant differences between the two genotypes in Beta-diversity. Furthermore, MPO-/- intestines were notably inflamed with significantly higher mucosal infiltrations of neutrophils and T cells, and significantly more fecal calprotectin. Despite no difference in epithelial tightness, MPO-/- intestines showed significantly slower movement than WT controls. Thus, MPO loss of function results in intestinal dysbiosis, inflammation and dysmobility. Funding Sources NIH HL150370; NIH AI185243 Topic Categories Innate Immune Responses and Host Defense: Molecular Mechanisms (INM)