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Intestinal microbiota modulates gluten-induced immunopathology in humanized mice

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Intestinal microbiota modulates gluten-induced immunopathology in humanized mice. / 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 G; Verdu, Elena F.

In: AM J PATHOL, Vol. 185, No. 11, 11.2015, p. 2969-82.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Galipeau, HJ, McCarville, JL, Huebener, S, Litwin, O, Meisel, M, Jabri, B, Sanz, Y, Murray, JA, Jordana, M, Alaedini, A, Chirdo, FG & Verdu, EF 2015, 'Intestinal microbiota modulates gluten-induced immunopathology in humanized mice', AM J PATHOL, vol. 185, no. 11, pp. 2969-82. https://doi.org/10.1016/j.ajpath.2015.07.018

APA

Galipeau, H. J., McCarville, J. L., Huebener, S., Litwin, O., Meisel, M., Jabri, B., Sanz, Y., Murray, J. A., Jordana, M., Alaedini, A., Chirdo, F. G., & Verdu, E. F. (2015). Intestinal microbiota modulates gluten-induced immunopathology in humanized mice. AM J PATHOL, 185(11), 2969-82. https://doi.org/10.1016/j.ajpath.2015.07.018

Vancouver

Galipeau HJ, McCarville JL, Huebener S, Litwin O, Meisel M, Jabri B et al. Intestinal microbiota modulates gluten-induced immunopathology in humanized mice. AM J PATHOL. 2015 Nov;185(11):2969-82. https://doi.org/10.1016/j.ajpath.2015.07.018

Bibtex

@article{cf13e1d9d00d497eb2f303693ca1cea5,
title = "Intestinal microbiota modulates gluten-induced immunopathology in humanized mice",
abstract = "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. ",
keywords = "Animals, Anti-Bacterial Agents, Antibodies, Celiac Disease, Cell Proliferation, Cytokines, Feces, Female, Gastrointestinal Microbiome, Gliadin, Glutens, Humans, Male, Mice, Mice, Inbred NOD, Specific Pathogen-Free Organisms, T-Lymphocytes, Vancomycin, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't",
author = "Galipeau, {Heather J} and McCarville, {Justin L} and Sina Huebener and Owen Litwin and Marlies Meisel and Bana Jabri and Yolanda Sanz and Murray, {Joseph A} and Manel Jordana and Armin Alaedini and Chirdo, {Fernando G} and Verdu, {Elena F}",
note = "Copyright {\textcopyright} 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.",
year = "2015",
month = nov,
doi = "10.1016/j.ajpath.2015.07.018",
language = "English",
volume = "185",
pages = "2969--82",
journal = "AM J PATHOL",
issn = "0002-9440",
publisher = "Elsevier Inc.",
number = "11",

}

RIS

TY - JOUR

T1 - Intestinal microbiota modulates gluten-induced immunopathology in humanized mice

AU - Galipeau, Heather J

AU - McCarville, Justin L

AU - Huebener, Sina

AU - Litwin, Owen

AU - Meisel, Marlies

AU - Jabri, Bana

AU - Sanz, Yolanda

AU - Murray, Joseph A

AU - Jordana, Manel

AU - Alaedini, Armin

AU - Chirdo, Fernando G

AU - Verdu, Elena F

N1 - Copyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

PY - 2015/11

Y1 - 2015/11

N2 - 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.

AB - 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.

KW - Animals

KW - Anti-Bacterial Agents

KW - Antibodies

KW - Celiac Disease

KW - Cell Proliferation

KW - Cytokines

KW - Feces

KW - Female

KW - Gastrointestinal Microbiome

KW - Gliadin

KW - Glutens

KW - Humans

KW - Male

KW - Mice

KW - Mice, Inbred NOD

KW - Specific Pathogen-Free Organisms

KW - T-Lymphocytes

KW - Vancomycin

KW - Journal Article

KW - Research Support, N.I.H., Extramural

KW - Research Support, Non-U.S. Gov't

U2 - 10.1016/j.ajpath.2015.07.018

DO - 10.1016/j.ajpath.2015.07.018

M3 - SCORING: Journal article

C2 - 26456581

VL - 185

SP - 2969

EP - 2982

JO - AM J PATHOL

JF - AM J PATHOL

SN - 0002-9440

IS - 11

ER -