title: The gut microbiota engages different signaling pathways to induce Duox2 expression in the ileum and colon epithelium.
abstract: The epithelium is a first line of defense against microorganisms in the gut. Reactive oxygen species (ROS) have an important role in controlling the normal gut microbiota and pathogenic bacteria. Dual oxidase 2 (DUOX2) is an important source of hydrogen peroxide in the small and large intestine, and the gut microbiota induces Duox2 expression. Here, we investigated the microbial regulation of Duox2 expression. We found that Duox2 was expressed by intestinal epithelial cells mainly in the tip of the epithelium. Duox2 expression was strongly induced by the presence of a normal microbiota in mice, but not when germ-free mice were colonized with various commensal bacteria. Duox2 expression was more rapidly induced by the gut microbiota in the colon than in the ileum. Furthermore, we showed that regulation of Duox2 expression in the ileum involved TIR-domain-containing adaptor protein including interferon-β (TRIF) and canonical nuclear factor-κB p50/p65 signaling, whereas regulation of Duox2 expression in the colon involved MyD88 and the p38 pathway. Collectively, these data indicate that the gut microbiota uses two distinct signaling pathways to induce Duox2 expression in the ileum and colon epithelium.
authors.affiliation: The Wallenberg Laboratory and Sahlgrenska Center for Cardiovascular and Metabolic Research, Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden.
authors.forename: F
authors.initials: F
authors.lastname: Sommer
authors.affiliation: 1] The Wallenberg Laboratory and Sahlgrenska Center for Cardiovascular and Metabolic Research, Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden [2] Novo Nordisk Foundation Center for Basic Metabolic Research, Section for Metabolic Receptology and Enteroendocrinology, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: F
authors.initials: F
authors.lastname: Bäckhed
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D003092:Colitis / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D003106:Colon; D000074623:Dual Oxidases; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006801:Humans; D007082:Ileum; D053583:Interleukin-1beta / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000382:microbiology* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D064307:Microbiota; D019255:NADPH Oxidases / Q000235:genetics* / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D053583:Interleukin-1beta; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D000074623:Dual Oxidases; D019255:NADPH Oxidases; C519130:Duox1 protein, mouse; D048051:p38 Mitogen-Activated Protein Kinases