title: Gastrointestinal microbiota and local inflammation during oxazolone-induced dermatitis in BALB/cA mice.
abstract: At present, laboratory animals are not standardized with regard to the gastrointestinal microbiota (GM), but differences in this feature may alter various parameters in animal models. We hypothesized that variation in the GM correlated with variation in clinical parameters of a murine  oxazolone-induced skin inflammation model of atopic dermatitis. BALB/cA mice were sensitized with oxazolone over a 28-d period and variation in gastrointestinal microbiota in fecal and cecal samples was assessed by PCR-denaturing gradient gel electrophoresis. Clinical parameters included transepidermal  water loss, ear thickness, inflammatory factors in ear tissue and plasma, and histopathologic evaluation. The fecal microbiota before induction of skin inflammation strongly correlated with the levels of some proinflammatory cytokines (IFNγ, IL1β, IL12, and TNFα), the antiinflammatory  cytokines IL4 and IL10, and the chemokine KC/GRO that were measured in ear samples at study termination. Cecal microbiota at termination correlated with ear thickness and transepidermal water loss. There was no correlation between cytokine responses and ear thickness or transepidermal water  loss. In addition, GM changed during the study period in the oxazolone-treated mice, whereas this was not the case for the control mice. The current study shows that the GM of mice influences the development of oxazolone-induced skin inflammation and that the model itself likely induces a  pathophysiologic response that alters the composition of the GM.
authors.affiliation: Centre for Applied Laboratory Animal Research, Section of Biomedicine, Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. randi@randises.dk
authors.forename: Randi
authors.initials: R
authors.lastname: Lundberg
authors.forename: Susanne K
authors.initials: SK
authors.lastname: Clausen
authors.forename: Wanyong
authors.initials: W
authors.lastname: Pang
authors.forename: Dennis S
authors.initials: DS
authors.lastname: Nielsen
authors.forename: Kristian
authors.initials: K
authors.lastname: Möller
authors.forename: Knud E
authors.initials: KE
authors.lastname: Josefsen
authors.forename: Axel K
authors.initials: AK
authors.lastname: Hansen
mesh_terms: D000818:Animals; D002432:Cecum / Q000382:microbiology; D016207:Cytokines / Q000378:metabolism; D058645:Denaturing Gradient Gel Electrophoresis; D003876:Dermatitis, Atopic / Q000139:chemically induced / Q000382:microbiology*; D004423:Ear / Q000473:pathology; D005243:Feces / Q000382:microbiology; D005260:Female; D041981:Gastrointestinal Tract / Q000382:microbiology*; D054892:Metagenome / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D010081:Oxazolone / Q000633:toxicity; D025341:Principal Component Analysis; D012044:Regression Analysis; D014870:Water Loss, Insensible / Q000502:physiology
chemical_list: D016207:Cytokines; D010081:Oxazolone