Delayed Gut Colonization Shapes Future Allergic Responses in a Murine Model of Atopic Dermatitis
Epidemiological studies have long reported that perturbations of the childhood microbiome increase the risk of developing allergies, but a causal relationship with atopic dermatitis remains unclear. Here we colonized germ-free mice at birth or at one or eight week-of-age to investigate the role of p...
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doaj-59e67aee7d5e46bf8c4b00cc3bf6e0222021-03-17T05:47:36ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-03-011210.3389/fimmu.2021.650621650621Delayed Gut Colonization Shapes Future Allergic Responses in a Murine Model of Atopic DermatitisAmalie W. Arildsen0Line F. Zachariassen1Lukasz Krych2Axel K. Hansen3Camilla H. F. Hansen4Section of Experimental Animal Models, Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg, DenmarkSection of Experimental Animal Models, Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg, DenmarkDepartment of Food Science, Faculty of Science, University of Copenhagen, Frederiksberg, DenmarkSection of Experimental Animal Models, Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg, DenmarkSection of Experimental Animal Models, Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg, DenmarkEpidemiological studies have long reported that perturbations of the childhood microbiome increase the risk of developing allergies, but a causal relationship with atopic dermatitis remains unclear. Here we colonized germ-free mice at birth or at one or eight week-of-age to investigate the role of prenatal and early postnatal microbial exposure on development of oxozolone-induced dermatitis later in life. We demonstrate that only one week delayed microbial colonization increased IgE levels and the total histological score of the inflamed ear compared to mice colonized throughout life. In parallel, several pro-inflammatory cytokines and chemokines were upregulated in the ear tissue demonstrating an enhanced immunological response following delayed postnatal colonization of the gut. In contrast, sensitivity to oxazolone-induced dermatitis was unaffected by the presence of a maternal microbiota during gestation. Mice colonized at eight week-of-age failed to colonize Rikenellaceae, a group of bacteria previously associated with a high-responding phenotype, and did not develop an immunological response to the same extent as the early colonized mice despite pronounced histopathological manifestations. The study provides proof-of-principle that the first intestinal colonizers of mice pups are crucial for the development of oxazolone-induced dermatitis later in life, and that the status of the maternal microbiota during pregnancy has no influence on the offspring’s allergic immune response. This highlights an important window of opportunity following birth for microbiota-mediated interventions to prevent atopic responses later in life. How long such a window is open may vary between mice and humans considering species differences in the ontogeny of the immune system.https://www.frontiersin.org/articles/10.3389/fimmu.2021.650621/fullallergyatopic dermatitischildhood ezcemaearly priminggut microbiotaimmune maturation |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Amalie W. Arildsen Line F. Zachariassen Lukasz Krych Axel K. Hansen Camilla H. F. Hansen |
spellingShingle |
Amalie W. Arildsen Line F. Zachariassen Lukasz Krych Axel K. Hansen Camilla H. F. Hansen Delayed Gut Colonization Shapes Future Allergic Responses in a Murine Model of Atopic Dermatitis Frontiers in Immunology allergy atopic dermatitis childhood ezcema early priming gut microbiota immune maturation |
author_facet |
Amalie W. Arildsen Line F. Zachariassen Lukasz Krych Axel K. Hansen Camilla H. F. Hansen |
author_sort |
Amalie W. Arildsen |
title |
Delayed Gut Colonization Shapes Future Allergic Responses in a Murine Model of Atopic Dermatitis |
title_short |
Delayed Gut Colonization Shapes Future Allergic Responses in a Murine Model of Atopic Dermatitis |
title_full |
Delayed Gut Colonization Shapes Future Allergic Responses in a Murine Model of Atopic Dermatitis |
title_fullStr |
Delayed Gut Colonization Shapes Future Allergic Responses in a Murine Model of Atopic Dermatitis |
title_full_unstemmed |
Delayed Gut Colonization Shapes Future Allergic Responses in a Murine Model of Atopic Dermatitis |
title_sort |
delayed gut colonization shapes future allergic responses in a murine model of atopic dermatitis |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2021-03-01 |
description |
Epidemiological studies have long reported that perturbations of the childhood microbiome increase the risk of developing allergies, but a causal relationship with atopic dermatitis remains unclear. Here we colonized germ-free mice at birth or at one or eight week-of-age to investigate the role of prenatal and early postnatal microbial exposure on development of oxozolone-induced dermatitis later in life. We demonstrate that only one week delayed microbial colonization increased IgE levels and the total histological score of the inflamed ear compared to mice colonized throughout life. In parallel, several pro-inflammatory cytokines and chemokines were upregulated in the ear tissue demonstrating an enhanced immunological response following delayed postnatal colonization of the gut. In contrast, sensitivity to oxazolone-induced dermatitis was unaffected by the presence of a maternal microbiota during gestation. Mice colonized at eight week-of-age failed to colonize Rikenellaceae, a group of bacteria previously associated with a high-responding phenotype, and did not develop an immunological response to the same extent as the early colonized mice despite pronounced histopathological manifestations. The study provides proof-of-principle that the first intestinal colonizers of mice pups are crucial for the development of oxazolone-induced dermatitis later in life, and that the status of the maternal microbiota during pregnancy has no influence on the offspring’s allergic immune response. This highlights an important window of opportunity following birth for microbiota-mediated interventions to prevent atopic responses later in life. How long such a window is open may vary between mice and humans considering species differences in the ontogeny of the immune system. |
topic |
allergy atopic dermatitis childhood ezcema early priming gut microbiota immune maturation |
url |
https://www.frontiersin.org/articles/10.3389/fimmu.2021.650621/full |
work_keys_str_mv |
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