A gut pathobiont synergizes with the microbiota to instigate inflammatory disease marked by immunoreactivity against other symbionts but not itself

Authors

João Carlos Gomes-Neto, University of Nebraska-LincolnFollow
Hatem Kittana, University of Nebraska-Lincoln
Sara Mantz, University of Nebraska-Lincoln
Rafael R. Segura Munoz, University of Nebraska-LincolnFollow
Robert J. Schmaltz, University of Nebraska - LincolnFollow
Laure B. Bindels, University of Nebraska-Lincoln
Jennifer L. Clarke, University of Nebraska-LincolnFollow
Jesse M. Hostetter, Iowa State UniversityFollow
Andrew K. Benson, University of Nebraska-LincolnFollow
Jens Walter, University of Nebraska-LincolnFollow
Amanda Ramer-Tait, University of Nebraska-LincolnFollow

ORCID IDs

Jennifer L. Clarke

Document Type

Article

Date of this Version

12-18-2017

Citation

Scientific Reports (2017) 7:17707

DOI 10.1038/s41598-017-18014-5

Comments

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License. © The Author(s) 2017

Abstract

Inflammatory bowel diseases (IBD) are likely driven by aberrant immune responses directed against the resident microbiota. Although IBD is commonly associated with a dysbiotic microbiota enriched in putative pathobionts, the etiological agents of IBD remain unknown. Using a pathobiont-induced intestinal inflammation model and a defined bacterial community, we provide new insights into the immune-microbiota interactions during disease. In this model system, the pathobiont Helicobacter bilis instigates disease following sub-pathological dextran sulfate sodium treatment. We show that H. bilis causes mild inflammation in mono-associated mice, but severe disease in the presence of a microbiota, demonstrating synergy between the pathobiont and microbiota in exacerbating pathology. Remarkably, inflammation depends on the presence of H. bilis, but is marked by a predominant Th17 response against specific members of the microbiota and not the pathobiont, even upon the removal of the most immune-dominant taxa. Neither increases in pathobiont burden nor unique changes in immune-targeted microbiota member abundances are observed during disease. Collectively, our findings demonstrate that a pathobiont instigates inflammation without being the primary target of a Th17 response or by altering the microbiota community structure. Moreover, our findings point toward monitoring pathobiont-induced changes in microbiota immune targeting as a new concept in IBD diagnotics.