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

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

Document Type Article

Open Access.

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.