Intestinal Microbiota Modulates Gluten-Induced Immunopathology in Humanized Mice

Celiac disease (CD) is an immune-mediated enteropathy triggered by gluten in genetically susceptible individuals. The recent increase in CD incidence suggests that additional environmental factors, such as intestinal microbiota alterations, are involved in its pathogenesis. However, there is no dire...

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Autores principales: Galipeau, Heather J., McCarville, Justin L., Huebener, Sina, Litwin, Owen, Meisel, Marlies, Jabri, Bana, Sanz, Yolanda, Murray, Joseph A., Jordana, Manel, Alaedini, Armin, Chirdo, Fernando Gabriel, Verdu, Elena F.
Formato: Articulo
Lenguaje:Inglés
Publicado: 2015
Materias:
Biología
Ciencias Médicas
Celiac disease
Microbiota
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/128604
Aporte de:
SEDICI (UNLP) de Universidad Nacional de La Plata
id I19-R120-10915-128604
record_format dspace
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Biología
Ciencias Médicas
Celiac disease
Microbiota
spellingShingle Biología
Ciencias Médicas
Celiac disease
Microbiota
Galipeau, Heather J.
McCarville, Justin L.
Huebener, Sina
Litwin, Owen
Meisel, Marlies
Jabri, Bana
Sanz, Yolanda
Murray, Joseph A.
Jordana, Manel
Alaedini, Armin
Chirdo, Fernando Gabriel
Verdu, Elena F.
Intestinal Microbiota Modulates Gluten-Induced Immunopathology in Humanized Mice
topic_facet Biología
Ciencias Médicas
Celiac disease
Microbiota
description Celiac disease (CD) is an immune-mediated enteropathy triggered by gluten in genetically susceptible individuals. The recent increase in CD incidence suggests that additional environmental factors, such as intestinal microbiota alterations, are involved in its pathogenesis. However, there is no direct evidence of modulation of gluten-induced immunopathology by the microbiota. We investigated whether specific microbiota compositions influence immune responses to gluten in mice expressing the human DQ8 gene, which confers moderate CD genetic susceptibility. Germ-free mice, clean specific-pathogen-free (SPF) mice colonized with a microbiota devoid of opportunistic pathogens and Proteobacteria, and conventional SPF mice that harbor a complex microbiota that includes opportunistic pathogens were used. Clean SPF mice had attenuated responses to gluten compared to germ-free and conventional SPF mice. Germ-free mice developed increased intraepithelial lymphocytes, markers of intraepithelial lymphocyte cytotoxicity, gliadin-specific antibodies, and a proinflammatory gliadin-specific T-cell response. Antibiotic treatment, leading to Proteobacteria expansion, further enhanced gluten-induced immunopathology in conventional SPF mice. Protection against gluten-induced immunopathology in clean SPF mice was reversed after supplementation with a member of the Proteobacteria phylum, an enteroadherent Escherichia coli isolated from a CD patient. The intestinal microbiota can both positively and negatively modulate gluten-induced immunopathology in mice. In subjects with moderate genetic susceptibility, intestinal microbiota changes may be a factor that increases CD risk.
format Articulo
Articulo
author Galipeau, Heather J.
McCarville, Justin L.
Huebener, Sina
Litwin, Owen
Meisel, Marlies
Jabri, Bana
Sanz, Yolanda
Murray, Joseph A.
Jordana, Manel
Alaedini, Armin
Chirdo, Fernando Gabriel
Verdu, Elena F.
author_facet Galipeau, Heather J.
McCarville, Justin L.
Huebener, Sina
Litwin, Owen
Meisel, Marlies
Jabri, Bana
Sanz, Yolanda
Murray, Joseph A.
Jordana, Manel
Alaedini, Armin
Chirdo, Fernando Gabriel
Verdu, Elena F.
author_sort Galipeau, Heather J.
title Intestinal Microbiota Modulates Gluten-Induced Immunopathology in Humanized Mice
title_short Intestinal Microbiota Modulates Gluten-Induced Immunopathology in Humanized Mice
title_full Intestinal Microbiota Modulates Gluten-Induced Immunopathology in Humanized Mice
title_fullStr Intestinal Microbiota Modulates Gluten-Induced Immunopathology in Humanized Mice
title_full_unstemmed Intestinal Microbiota Modulates Gluten-Induced Immunopathology in Humanized Mice
title_sort intestinal microbiota modulates gluten-induced immunopathology in humanized mice
publishDate 2015
url http://sedici.unlp.edu.ar/handle/10915/128604
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