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

Scientific Reports. 2017;7(1):1-14 DOI 10.1038/s41598-017-18014-5

 

Journal Homepage

Journal Title: Scientific Reports

ISSN: 2045-2322 (Online)

Publisher: Nature Publishing Group

LCC Subject Category: Medicine | Science

Country of publisher: United Kingdom

Language of fulltext: English

Full-text formats available: PDF, HTML

 

AUTHORS


João Carlos Gomes-Neto (Department of Food Science and Technology, University of Nebraska-Lincoln)

Hatem Kittana (Department of Food Science and Technology, University of Nebraska-Lincoln)

Sara Mantz (Department of Food Science and Technology, University of Nebraska-Lincoln)

Rafael R. Segura Munoz (Department of Food Science and Technology, University of Nebraska-Lincoln)

Robert J. Schmaltz (Department of Food Science and Technology, University of Nebraska-Lincoln)

Laure B. Bindels (Department of Food Science and Technology, University of Nebraska-Lincoln)

Jennifer Clarke (Department of Food Science and Technology, University of Nebraska-Lincoln)

Jesse M. Hostetter (Department of Veterinary Pathology, College of Veterinary Medicine, Iowa State University)

Andrew K. Benson (Department of Food Science and Technology, University of Nebraska-Lincoln)

Jens Walter (Department of Agricultural, Food and Nutritional Science, University of Alberta)

Amanda E. Ramer-Tait (Department of Food Science and Technology, University of Nebraska-Lincoln)

EDITORIAL INFORMATION

Blind peer review

Editorial Board

Instructions for authors

Time From Submission to Publication: 20 weeks

 

Abstract | Full Text

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.