Postnatal supplementation with alarmins S100a8/a9 ameliorates malnutrition-induced neonate enteropathy in mice.
Animals
Calgranulin A
/ metabolism
Calgranulin B
/ metabolism
Female
Mice
Malnutrition
/ complications
Animals, Newborn
Gastrointestinal Microbiome
Intestinal Diseases
/ metabolism
Mice, Inbred C57BL
Disease Models, Animal
Male
Dietary Supplements
Intestinal Mucosa
/ metabolism
Pregnancy
Neutrophils
/ immunology
Immunity, Mucosal
Humans
Intestines
/ microbiology
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
04 Oct 2024
04 Oct 2024
Historique:
received:
19
12
2023
accepted:
19
09
2024
medline:
5
10
2024
pubmed:
5
10
2024
entrez:
4
10
2024
Statut:
epublish
Résumé
Malnutrition is linked to 45% of global childhood mortality, however, the impact of maternal malnutrition on the child's health remains elusive. Previous studies suggested that maternal malnutrition does not affect breast milk composition. Yet, malnourished children often develop a so-called environmental enteropathy, assumed to be triggered by frequent pathogen uptake and unfavorable gut colonization. Here, we show in a murine model that maternal malnutrition induces a persistent inflammatory gut dysfunction in the offspring that establishes during nursing and does not recover after weaning onto standard diet. Early intestinal influx of neutrophils, impaired postnatal development of gut-regulatory functions, and expansion of Enterobacteriaceae were hallmarks of this enteropathy. This gut phenotype resembled those developing under deficient S100a8/a9-supply via breast milk, which is a known key factor for the postnatal development of gut homeostasis. We could confirm that S100a8/a9 is lacking in the breast milk of malnourished mothers and the offspring's intestine. Nutritional supply of S100a8 to neonates of malnourished mothers abrogated the aberrant development of gut mucosal immunity and microbiota colonization and protected them lifelong against severe enteric infections and non-infectious bowel diseases. S100a8 supplementation after birth might be a promising measure to counteract deleterious imprinting of gut immunity by maternal malnutrition.
Identifiants
pubmed: 39366940
doi: 10.1038/s41467-024-52829-x
pii: 10.1038/s41467-024-52829-x
doi:
Substances chimiques
Calgranulin A
0
Calgranulin B
0
S100a8 protein, mouse
0
S100A9 protein, mouse
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
8623Subventions
Organisme : Bill & Melinda Gates Foundation
ID : INV-004078
Pays : United States
Organisme : Bill & Melinda Gates Foundation
ID : INV-004078
Pays : United States
Organisme : Bundesministerium für Bildung und Forschung (Federal Ministry of Education and Research)
ID : 01EK2103A
Organisme : Bundesministerium für Bildung und Forschung (Federal Ministry of Education and Research)
ID : 01EK2103D
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : VI 538/6-3, VI 538-9-1, 492620490, 491676693, 390874280
Organisme : Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (Swiss National Science Foundation)
ID : 310030_192531
Informations de copyright
© 2024. The Author(s).
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