A Specific Mutation in Muc2 Determines Early Dysbiosis in Colitis-Prone Winnie Mice

Host: Ivy Ka Man Law, PhD
A Specific Mutation in Muc2 Determines Early Dysbiosis in Colitis-Prone Winnie Mice Marina Liso, Stefania De Santis, Giulio Verna, Manuela Dicarlo, Maria Calasso, Angelo Santino, Isabella Gigante, Rajaraman Eri, Sathuwarman Raveenthiraraj, Anastasia Sobolewski, Valeria Palmitessa, Antonio Lippolis, Mauro Mastronardi, Raffaele Armentano, Grazia Serino, Maria De Angelis, Marcello Chieppa Background: Inflammatory bowel disease (IBD), including Crohn disease (CD) and ulcerative colitis (UC), is a multifactorial disorder characterized by chronic inflammation and altered gut barrier function. Dysbiosis, a condition defined by dysregulation of the gut microbiome, has been reported in patients with IBD and in experimental models of colitis. Although several factors have been implicated in directly affecting gut microbial composition, the genetic determinants impacting intestinal dysbiosis in IBD remain relatively unknown. Methods: We compared the microbiome of normal, uninflamed wild-type (WT) mice with that of a murine model of UC (ie, Winnie strain). Winnie mice possess a missense mutation in Muc2 that manifests in altered mucus production as early as 4 weeks of age, with ensuing colonic inflammation. To better address the potential role of mutant Muc2 in promoting dysbiosis in Winnie mice, we evaluated homozygous mutant mice (Winnie-/-) with their WT littermates that, after weaning from common mothers, were caged …