Cited by 682Gut microbiota and healthT-cell and B-cell ImmunologyImmune Response and Inflammation

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A Weaning Reaction to Microbiota Is Required for Resistance to Immunopathologies in the Adult

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Al Nabhani, Ziad, Dulauroy, Sophie, Marques, Rute, Cousu, Clara, Al Bounny, Shahed, Déjardin, François, Sparwasser, Tim, Bérard, Marion, Cerf-Bensussan, Nadine, Eberl, Gérard·2019·Immunity

DOI 10.1016/j.immuni.2019.02.014

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Abstract

Microbes colonize all body surfaces at birth and participate in the development of the immune system. In newborn mammals, the intestinal microbiota is first shaped by the dietary and immunological components of milk and then changes upon the introduction of solid food during weaning. Here, we explored the reactivity of the mouse intestinal immune system during the first weeks after birth and into adulthood. At weaning, the intestinal microbiota induced a vigorous immune response—a "weaning reaction"—that was programmed in time. Inhibition of the weaning reaction led to pathological imprinting and increased susceptibility to colitis, allergic inflammation, and cancer later in life. Prevention of this pathological imprinting was associated with the generation of RORγt + regulatory T cells, which required bacterial and dietary metabolites—short-chain fatty acids and retinoic acid. Thus, the weaning reaction to microbiota is required for immune ontogeny, the perturbation of which leads to increased susceptibility to immunopathologies later in life.

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Authors: Al Nabhani, Z., Dulauroy, S., Marques, R., Cousu, C., Al Bounny, S., Déjardin, F., Sparwasser, T., Bérard, M., Cerf-Bensussan, N., & Eberl, G.
Affiliations: Inserm (FR)
Johannes Gutenberg University Mainz (DE)
Corresponding author: Eberl, Gérard
ORCID: Cousu, Clara
Déjardin, François
Sparwasser, Tim
Eberl, Gérard
Venue: Immunity
Publisher: Elsevier BV
Published: 2019-05
Volume: 50
Issue: 5
Pages: 1276-1288.e5
ISSN: 1074-7613 (ISSN-L)
DOI: 10.1016/j.immuni.2019.02.014
OpenAlex: W2924644564
Cited by: 679
References: 48
Citations by year: 2026: 87 · 2025: 99 · 2024: 109 · 2023: 100 · 2022: 89 · 2021: 98 · 2020: 64 · 2019: 33
FWCI: 23.50
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: other-oa
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 386 d)
Locations: Immunity (publishedVersion, other-oa)
PubMed (publishedVersion)
HAL (submittedVersion, cc-by-nc)
Oskar-Bordeaux (Universite de Bordeaux) (submittedVersion)
Funders: Institut Pasteur
INSERM
Association François Aupetit
Crohn's and Colitis Foundation of America
European Crohn’s and Colitis Organisation
Fondation pour la Recherche Médicale
Janssen
Kenneth Rainin Foundation
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Keywords: gut microbiota, immune ontogeny, immune system development, colitis, allergic inflammation, cancer susceptibility, short-chain fatty acids, retinoic acid, dietary metabolites, microbial colonization
MeSH terms: Gastrointestinal Microbiome, Animals, Animals, Newborn, Fatty Acids, Volatile, Intestinal Mucosa, Mice, Inbred C57BL, Tretinoin, Weaning, T-Lymphocytes, Regulatory, Mice, Nuclear Receptor Subfamily 1, Group F, Member 3

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A Weaning Reaction to Microbiota Is Required for Resistance to Immunopathologies in the Adult

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