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

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

Research output: Contribution to journalArticle

6 Citations (Scopus)

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.

Original languageEnglish (US)
Article number17707
JournalScientific reports
Volume7
Issue number1
DOIs
StatePublished - Dec 1 2017

Fingerprint

Microbiota
Inflammatory Bowel Diseases
Inflammation
Helicobacter
Dextran Sulfate
Pathology

ASJC Scopus subject areas

  • General

Cite this

A gut pathobiont synergizes with the microbiota to instigate inflammatory disease marked by immunoreactivity against other symbionts but not itself. / Gomes-Neto, João Carlos; Kittana, Hatem; Mantz, Sara; Segura Munoz, Rafael R.; Schmaltz, Robert J.; Bindels, Laure B.; Clarke, Jennifer; Hostetter, Jesse M.; Benson, Andrew K.; Walter, Jens; Ramer-Tait, Amanda E.

In: Scientific reports, Vol. 7, No. 1, 17707, 01.12.2017.

Research output: Contribution to journalArticle

Gomes-Neto, João Carlos ; Kittana, Hatem ; Mantz, Sara ; Segura Munoz, Rafael R. ; Schmaltz, Robert J. ; Bindels, Laure B. ; Clarke, Jennifer ; Hostetter, Jesse M. ; Benson, Andrew K. ; Walter, Jens ; Ramer-Tait, Amanda E. / A gut pathobiont synergizes with the microbiota to instigate inflammatory disease marked by immunoreactivity against other symbionts but not itself. In: Scientific reports. 2017 ; Vol. 7, No. 1.
@article{c815273356c045c9910f466767b8a524,
title = "A gut pathobiont synergizes with the microbiota to instigate inflammatory disease marked by immunoreactivity against other symbionts but not itself",
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.",
author = "Gomes-Neto, {Jo{\~a}o Carlos} and Hatem Kittana and Sara Mantz and {Segura Munoz}, {Rafael R.} and Schmaltz, {Robert J.} and Bindels, {Laure B.} and Jennifer Clarke and Hostetter, {Jesse M.} and Benson, {Andrew K.} and Jens Walter and Ramer-Tait, {Amanda E.}",
year = "2017",
month = "12",
day = "1",
doi = "10.1038/s41598-017-18014-5",
language = "English (US)",
volume = "7",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
number = "1",

}

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.

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.

UR - http://www.scopus.com/inward/record.url?scp=85038589552&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85038589552&partnerID=8YFLogxK

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 -