Intestinal microbiota modulates gluten-induced immunopathology in humanized mice

Autores
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.
Año de publicación
2015
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
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.
Fil: Galipeau, Heather J.. McMaster University; Canadá
Fil: McCarville, Justin L.. McMaster University; Canadá
Fil: Huebener, Sina. Columbia University Medical Center; Estados Unidos
Fil: Litwin, Owen. McMaster University; Canadá
Fil: Meisel, Marlies. University of Chicago; Estados Unidos
Fil: Jabri, Bana. University of Chicago; Estados Unidos
Fil: Sanz, Yolanda. Consejo Superior de Investigaciones Científicas. Instituto de Agroquímica y Tecnología de Alimentos; España
Fil: Murray, Joseph A.. Mayo Clinic College of Medicine and Science; Estados Unidos
Fil: Jordana, Manel. McMaster University; Canadá
Fil: Alaedini, Armin. Columbia University Medical Center; Estados Unidos
Fil: Chirdo, Fernando Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Estudios Inmunológicos y Fisiopatológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Estudios Inmunológicos y Fisiopatológicos; Argentina
Fil: Verdu, Elena F.. McMaster University; Canadá
Materia
celiac disease
microbiota
mucosal immunity
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/100356
Acceder
id CONICETDig_47a257bb2d5739b6c7297f42f44fd6f6
oai_identifier_str oai:ri.conicet.gov.ar:11336/100356
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Intestinal microbiota modulates gluten-induced immunopathology in humanized miceGalipeau, Heather J.McCarville, Justin L.Huebener, SinaLitwin, OwenMeisel, MarliesJabri, BanaSanz, YolandaMurray, Joseph A.Jordana, ManelAlaedini, ArminChirdo, Fernando GabrielVerdu, Elena F.celiac diseasemicrobiotamucosal immunityhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Celiac 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.Fil: Galipeau, Heather J.. McMaster University; CanadáFil: McCarville, Justin L.. McMaster University; CanadáFil: Huebener, Sina. Columbia University Medical Center; Estados UnidosFil: Litwin, Owen. McMaster University; CanadáFil: Meisel, Marlies. University of Chicago; Estados UnidosFil: Jabri, Bana. University of Chicago; Estados UnidosFil: Sanz, Yolanda. Consejo Superior de Investigaciones Científicas. Instituto de Agroquímica y Tecnología de Alimentos; EspañaFil: Murray, Joseph A.. Mayo Clinic College of Medicine and Science; Estados UnidosFil: Jordana, Manel. McMaster University; CanadáFil: Alaedini, Armin. Columbia University Medical Center; Estados UnidosFil: Chirdo, Fernando Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Estudios Inmunológicos y Fisiopatológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Estudios Inmunológicos y Fisiopatológicos; ArgentinaFil: Verdu, Elena F.. McMaster University; CanadáAmerican Society of Investigative Pathology2015-11info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/100356Galipeau, Heather J.; McCarville, Justin L.; Huebener, Sina; Litwin, Owen; Meisel, Marlies; et al.; Intestinal microbiota modulates gluten-induced immunopathology in humanized mice; American Society of Investigative Pathology; American Journal Of Pathology; 185; 11; 11-2015; 2969-29820002-9440CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.ajpath.2015.07.018info:eu-repo/semantics/altIdentifier/url/https://ajp.amjpathol.org/article/S0002-9440(15)00476-9/fulltextinfo:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4630176/info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:47:16Zoai:ri.conicet.gov.ar:11336/100356instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 09:47:16.965CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Intestinal microbiota modulates gluten-induced immunopathology in humanized mice
title Intestinal microbiota modulates gluten-induced immunopathology in humanized mice
spellingShingle Intestinal microbiota modulates gluten-induced immunopathology in humanized mice
Galipeau, Heather J.
celiac disease
microbiota
mucosal immunity
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
dc.creator.none.fl_str_mv 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 Galipeau, Heather J.
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_role author
author2 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.
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv celiac disease
microbiota
mucosal immunity
topic celiac disease
microbiota
mucosal immunity
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv 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.
Fil: Galipeau, Heather J.. McMaster University; Canadá
Fil: McCarville, Justin L.. McMaster University; Canadá
Fil: Huebener, Sina. Columbia University Medical Center; Estados Unidos
Fil: Litwin, Owen. McMaster University; Canadá
Fil: Meisel, Marlies. University of Chicago; Estados Unidos
Fil: Jabri, Bana. University of Chicago; Estados Unidos
Fil: Sanz, Yolanda. Consejo Superior de Investigaciones Científicas. Instituto de Agroquímica y Tecnología de Alimentos; España
Fil: Murray, Joseph A.. Mayo Clinic College of Medicine and Science; Estados Unidos
Fil: Jordana, Manel. McMaster University; Canadá
Fil: Alaedini, Armin. Columbia University Medical Center; Estados Unidos
Fil: Chirdo, Fernando Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Estudios Inmunológicos y Fisiopatológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Estudios Inmunológicos y Fisiopatológicos; Argentina
Fil: Verdu, Elena F.. McMaster University; Canadá
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.
publishDate 2015
dc.date.none.fl_str_mv 2015-11
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/100356
Galipeau, Heather J.; McCarville, Justin L.; Huebener, Sina; Litwin, Owen; Meisel, Marlies; et al.; Intestinal microbiota modulates gluten-induced immunopathology in humanized mice; American Society of Investigative Pathology; American Journal Of Pathology; 185; 11; 11-2015; 2969-2982
0002-9440
CONICET Digital
CONICET
url http://hdl.handle.net/11336/100356
identifier_str_mv Galipeau, Heather J.; McCarville, Justin L.; Huebener, Sina; Litwin, Owen; Meisel, Marlies; et al.; Intestinal microbiota modulates gluten-induced immunopathology in humanized mice; American Society of Investigative Pathology; American Journal Of Pathology; 185; 11; 11-2015; 2969-2982
0002-9440
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1016/j.ajpath.2015.07.018
info:eu-repo/semantics/altIdentifier/url/https://ajp.amjpathol.org/article/S0002-9440(15)00476-9/fulltext
info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4630176/
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv American Society of Investigative Pathology
publisher.none.fl_str_mv American Society of Investigative Pathology
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
_version_ 1842268847826010112
score 13.13397

Publicaciones similares