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

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 +2 more·2019·Immunity

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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Crossref · 10.1016/j.immuni.2019.02.014

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  • Altering the timing of weaning could result in a pathological imprinting of the immune response and increased susceptibility to later immunopathologies.

    “Altering the timing of weaning could result in a pathological imprinting of the immune response and increased susceptibility to later immunopathologies (270).”
  • Rapid development of the microbiota at weaning is observed across species and is critical for protection against later development of immunopathology in mice.

    “This rapid development at weaning is observed across species and was recently shown to be critical for protection against later development of immunopathology in mice (Al Nabhani et al., 2019).”

    From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Al Nabhani et al., 2019

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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
Venue
Immunity
Publisher
Elsevier BV
Published
2019-05
Volume
50
Issue
5
Pages
1276-1288.e5
ISSN
1074-7613 (ISSN-L)
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
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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