host genetics and environmental factors regulate ecological succession of the mouse colon tissue-associated microbiota宿主遗传和环境因素调节生态演替的小鼠结肠tissue-associated微生物群.pdfVIP

Host Genetics and Environmental Factors Regulate Ecological Succession of the Mouse Colon Tissue- Associated Microbiota 1. 1. 1. 2 1 1 Philip Smith , Jay Siddharth , Ruth Pearson , Nicholas Holway , Mark Shaxted , Matt Butler , Natalie 1 1 1 1 1,3 Clark , Joanna Jamontt , Robert P. Watson , Devika Sanmugalingam , Scott J. Parkinson * 1 Novartis Institutes for Biomedical Research, Gastrointestinal Disease Area, Horsham, West Sussex, United Kingdom, 2 Novartis Institutes for Biomedical Research Information Technology, Horsham, West Sussex, United Kingdom, 3 Novartis Institutes for Biomedical Research, Developmental and Molecular Pathways, Basel, Switzerland Abstract Background: The integration of host genetics, environmental triggers and the microbiota is a recognised factor in the pathogenesis of barrier function diseases such as IBD. In order to determine how these factors interact to regulate the host immune response and ecological succession of the colon tissue-associated microbiota, we investigated the temporal interaction between the microbiota and the host following disruption of the colonic epithelial barrier. Methodology/Principal Findings: Oral administration of DSS was applied as a mechanistic model of environmental damage of the colon and the resulting inflammation characterized for various parameters over time in WT and Nod2 KO mice. Results: In WT mice, DSS damage exposed the host to the commensal flora and led to a migration of the tissue-associated bacteria from the epithelium to mucosal