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Front. Immunol. | doi: 10.3389/fimmu.2019.01708

Composition of the intestinal microbiota determines the outcome of virus-triggered colitis in mice

 Silvia Bolsega1,  Marijana Basic1, Anna Smoczek1,  Manuela Buettner1, Claudia Eberl2, Daniel Ahrens1,  Kodwo A. Odum1,  Bärbel Stecher2, 3 and Andre Bleich1*
  • 1Institut für Versuchstierkunde und Zentrales Tierlaboratorium, Medizinischen Hochschule Hannover, Germany
  • 2Max von Pettenkofer-Institut, Ludwig-Maximilians-Universität München, Germany
  • 3German Center for Infection Research (DZIF), partner site Munich, Germany

The intestinal microbiota is a complex ecosystem implicated in host health and disease. Inflammatory bowel disease (IBD) is a multifactorial chronic disorder of the gastrointestinal mucosa. Even though the exact mechanisms are still unknown, the intestinal microbiota is crucial in IBD development. We previously showed that murine norovirus (MNV) induces colitis in the Il10-deficient (Il10-/-) mouse model of IBD in a microbiota-dependent manner. Thus, in this study we analyzed whether distinct minimal bacterial consortia influence the outcome of MNV-triggered colitis in Il10-/- mice. Gnotobiotic Il10-/- mice associated with Oligo-Mouse-Microbiota 12 (OMM12) or Altered Schaedler Flora (ASF) developed little to no inflammatory lesions in the colon and cecum. MNV infection exacerbated colitis severity only in ASF-colonized mice, but not in those associated with OMM12. Four weeks after MNV infection, inflammatory lesions in ASF-colonized Il10-/- mice were characterized by epithelial hyperplasia, infiltration of inflammatory cells and increased barrier permeability. Co-colonization of ASF-colonized Il10-/- mice with segmented filamentous bacteria (SFB) abolished MNV-induced colitis, whereas histopathological scores in SFB-OMM12-co-colonized mice stayed unchanged. Moreover, SFB only colonized mice associated with ASF. The SFB-mediated protective effects in ASF-colonized mice involved enhanced activation of intestinal barrier defense mechanisms and mucosal immune responses in the chronic and acute phase of MNV infection. SFB colonization strengthened intestinal barrier function by increasing expression of tight junction proteins, antimicrobial peptides and mucus. Furthermore, SFB colonization enhanced the expression of pro-inflammatory cytokines such as Tnf, Il1, and Il12a, as well as the expression of the regulatory cytokine Tgf. Altogether, our results showed that MNV-triggered colitis depends on the microbial context.

Keywords: intestinal microbiota, Oligo-MM12, Murine norovirus (MNV), Il10-deficient mice, host-microbiota interactions, Segmented Filamentous Bacteria (SFB), Altered Schaedler Flora (ASF), Colitis

Received: 27 Mar 2019; Accepted: 08 Jul 2019.

Edited by:

Irma Schabussova, Institute of Specific Prophylaxis and Tropical Medicine, Center for Pathophysiology, Infectiology and Immunology, Medical University Vienna, Austria

Reviewed by:

Preben Boysen, Norwegian University of Life Sciences, Norway
Miloslav Kverka, Institute of Microbiology (ASCR), Czechia  

Copyright: © 2019 Bolsega, Basic, Smoczek, Buettner, Eberl, Ahrens, Odum, Stecher and Bleich. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Andre Bleich, Institut für Versuchstierkunde und Zentrales Tierlaboratorium, Medizinischen Hochschule Hannover, Hannover, Germany, bleich.andre@mh-hannover.de