ALTERED MICROBIAL BIOGEOGRAPHY IN INNATE IMMUNE-MEDIATED COLITIS

Abstract We have developed an innate immune model of colitis that occurs in the absence adaptive immunity, is early-onset, 100% penetrant, chronic, and dependent on microbes. villin-TNFAIP3 transgenic mice, crossed to RAG1-/- mice (aka TRAG mice) develop immune-mediated not observed or littermates. Antibiotic treatment prevents mice. Thus, we sought investigate microbes drive chronic immunity. To examine spatial organization bacteria, mucus intestinal epithelium, bacteria were localized Methyl-Carnoys-fixed sections WT, villin-TNFAIP3, colons layers collected by laser capture microdissection (LCM) for evaluation bacterial populations. test antibiotic effectiveness prevention, treated with single solutions ampicillin, neomycin, metronidazole, vancomycin, all antibiotics combined a cocktail, was scored along proximal-distal axis colon. Microbial populations gut compared between 16S sequencing. invasion layer abundant but WT LCM indicated subset microbes, classes Gammaproteobacteria Actinobacteria, over-represented These included increased abundance genera Serratia, Acinetobacter, Pseudomonas Corynebacterium decreased Bifidobacterium. Differences colon, neomycin being most effective prevention inflammation cecum, while ampicillin distal The communities distinct tightly grouped within proximal whereas this structure lost In gut, relative Firmicutes (mainly Lachnospiraceae Ruminococcacaea) Proteobacteria Helicobacteriaceae Desulfovibrionbacteriaceae) Actinobacteria Bifidobacteriaceae) Bacteroidetes Bacteroidales). Unlike axis. had higher Bifidobacterium animalis, acidifaciens Lactobacilli lower Lachnospiraceae, RAG1-/-mice. cross-sectional biogeography disrupted which may contribute model.