RT Journal Article
SR Electronic
T1 A gut pathobiont synergizes with the microbiota to instigate inflammatory disease marked by immunoreactivity against other symbionts but not itself
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 178038
DO 10.1101/178038
A1 João Carlos Gomes-Neto
A1 Hatem Kittana
A1 Sara Mantz
A1 Rafael R. Segura Munoz
A1 Robert J. Schmaltz
A1 Laure B. Bindels
A1 Jennifer Clarke
A1 Jesse M. Hostetter
A1 Andrew K. Benson
A1 Jens Walter
A1 Amanda E. Ramer-Tait
YR 2017
UL http://biorxiv.org/content/early/2017/08/18/178038.abstract
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 our 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.