Host and microbiota interactions are critical for development of murine Crohn's-like ileitis

Roulis M, Bongers G, Armaka M, Salviano T, He Z, Singh A, Seidler U, Becker C, Demengeot J, Furtado GC, Lira SA, Kollias G (2016)

Publication Type: Journal article

Publication year: 2016

Journal

Mucosal Immunology Nature Publishing Group: Open Access Hybrid Model Option A

Book Volume: 9

Pages Range: 787-97

Journal Issue: 3

DOI: 10.1038/mi.2015.102

Abstract

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(?ARE/+) mice is microbiota-dependent. Germ-free Tnf(?ARE/+) 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(?ARE/+) 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(?ARE/+) 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(?ARE/+) hosts, whereas dysbiosis in this model results from disease-associated alterations including loss of lysozyme-expressing Paneth cells.

Authors with CRIS profile

Christoph Becker Professur für Molekulare Gastroenterologie

Involved external institutions

Biomedical Sciences Research Center "Alexander Fleming" GR Greece (GR) Icahn School of Medicine at Mount Sinai US United States (USA) (US) Medizinische Hochschule Hannover (MHH) / Hannover Medical School DE Germany (DE) Instituto Gulbenkian de Ciência PT Portugal (PT)

How to cite

APA:

Roulis, M., Bongers, G., Armaka, M., Salviano, T., He, Z., Singh, A.,... Kollias, G. (2016). Host and microbiota interactions are critical for development of murine Crohn's-like ileitis. Mucosal Immunology, 9(3), 787-97. https://doi.org/10.1038/mi.2015.102

MLA:

Roulis, M., et al. "Host and microbiota interactions are critical for development of murine Crohn's-like ileitis." Mucosal Immunology 9.3 (2016): 787-97.

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