Roulis, MBongers, GArmaka, MSalviano, THe, ZSingh, ASeidler, UBecker, CDemengeot, JFurtado, G CLira, S AKollias, G2018-03-022018-03-022016-05Mucosal Immunology volume 9, pages 787–797 (2016) doi:10.1038/mi.2015.102http://hdl.handle.net/10400.7/845This deposit is composed by a publication in which the IGC's authors have had the role of collaboration (it's a collaboration publication). This type of deposit in ARCA is in restrictedAccess (it can't be in open access to the public), and can only be accessed by two ways: either by requesting a legal copy from the author (the email contact present in this deposit) or by visiting the following link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5027991/This publication hasn't any creative commons license associated.Deregulation of host-microbiota interactions in the gut is a pivotal characteristic of Crohn's disease. It remains unclear, however, whether commensals and/or the dysbiotic microbiota associated with pathology in humans are causally involved in Crohn's pathogenesis. Here, we show that Crohn's-like ileitis in Tnf(ΔARE/+) mice is microbiota-dependent. Germ-free Tnf(ΔARE/+) mice are disease-free and the microbiota and its innate recognition through Myd88 are indispensable for tumor necrosis factor (TNF) overexpression and disease initiation in this model. The epithelium of diseased mice shows no major defects in mucus barrier and paracellular permeability. However, Tnf(ΔARE/+) ileitis associates with the reduction of lysozyme-expressing Paneth cells, mediated by adaptive immune effectors. Furthermore, we show that established but not early ileitis in Tnf(ΔARE/+) mice involves defective expression of antimicrobials and dysbiosis, characterized by Firmicutes expansion, including epithelial-attaching segmented filamentous bacteria, and decreased abundance of Bacteroidetes. Microbiota modulation by antibiotic treatment at an early disease stage rescues ileitis. Our results suggest that the indigenous microbiota is sufficient to drive TNF overexpression and Crohn's ileitis in the genetically susceptible Tnf(ΔARE/+) hosts, whereas dysbiosis in this model results from disease-associated alterations including loss of lysozyme-expressing Paneth cells.engAnimalsCells, CulturedCrohn DiseaseDisease Models, AnimalDysbiosisGastrointestinal MicrobiomeHost-Pathogen InteractionsHumansIleitisIntestinal MucosaMiceMice, Inbred C57BLMice, KnockoutMyeloid Differentiation Factor 88Tumor Necrosis Factor-alphajournal article10.1038/mi.2015.102