TY - JOUR
T1 - A gut pathobiont synergizes with the microbiota to instigate inflammatory disease marked by immunoreactivity against other symbionts but not itself
AU - Gomes-Neto, João Carlos
AU - Kittana, Hatem
AU - Mantz, Sara
AU - Segura Munoz, Rafael R.
AU - Schmaltz, Robert J.
AU - Bindels, Laure B.
AU - Clarke, Jennifer
AU - Hostetter, Jesse M.
AU - Benson, Andrew K.
AU - Walter, Jens
AU - Ramer-Tait, Amanda E.
N1 - Funding Information:
We are extremely grateful for the technical expertise and skillful animal husbandry provided by Brandon White and the staff at the UNL Gnotobiotic Mouse Facility. We would also like to acknowledge the expert technical support provided by Dirk Anderson, UNL Center for Biotechnology Flow Cytometry Core. We especially wish to thank Dr. Michael Wannemuehler (Iowa State University) for generously providing founder ASF-bearing breeding C3H/HeN mice, ASF strains and H. bilis WiWa. We also thank Drs. Stephen Kachman, Jay Reddy and Deborah Brown from the University of Nebraska-Lincoln for helpful discussions. This work was supported by a Career Development Award from the Crohn’s and Colitis Foundation of America (grant # 3578), the National Institute of General Medical Sciences of the National Institutes of Health (1P20GM104320), and start-up funding from the University of Nebraska-Lincoln to A.E.R.T. L.B.B. was supported by a complementary post-doctoral grant awarded by the Fonds Spécial de Recherche, Université catholique de Louvain. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.
Publisher Copyright:
© 2017 The Author(s).
PY - 2017/12/1
Y1 - 2017/12/1
N2 - 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.
AB - 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.
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U2 - 10.1038/s41598-017-18014-5
DO - 10.1038/s41598-017-18014-5
M3 - Article
C2 - 29255158
AN - SCOPUS:85038589552
VL - 7
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
IS - 1
M1 - 17707
ER -