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A Weaning Reaction to Microbiota Is Required for Resistance to Immunopathologies in the Adult
Open accessAbstract
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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“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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“Altering the timing of weaning could result in a pathological imprinting of the immune response and increased susceptibility to later immunopathologies (270).”
From Diet and the Microbiota–Gut–Brain Axis: Sowing the Seeds of Good Mental Health (2021) · cites this paper as [270]
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“However, even after weaning, the microbiota continues to change (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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HLA-DQβ57, anti-insulin T cells and insulin mimicry in autoimmune diabetesPreprint
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TLR4 regulates proinflammatory intestinal immune responses mediated by an atopic gut microbiotaPreprint
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Maternal humoral factors modulate offspring gut immune homeostasis to mitigate diabetes developmentPreprint
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The microbiota extends the reproductive lifespan by safeguarding the ovarian reservePreprint
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The role of gut microbiota in intestinal immune tolerance
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Epigenetic Shifts in Preterm Neonatal Microbiome
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Dendritic Cells: at the Crossroads between Oral Tolerance and Food Allergy
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Multifaceted Role of ILCs in Metabolic Adaptations: From Adult to Neonate
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Development of intestinal tissue-resident T cells in early-life mice before and after weaning
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Metadata
- 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
- hybrid
- doi.org
- Licence
- 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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