Postnatal supplementation with alarmins S100a8/a9 ameliorates malnutrition-induced neonate enteropathy in mice.

Autor: Perruzza L; Institute for Research in Biomedicine, Faculty of Biomedical Sciences, Università della Svizzera Italiana (USI), Bellinzona, Switzerland. lperruzza@vir.bio.; Humabs BioMed SA a Subsidiary of Vir Biotechnology Inc., Bellinzona, Switzerland. lperruzza@vir.bio., Heckmann J; Department of Pediatrics, University Hospital Würzburg, Würzburg, Germany., Rezzonico Jost T; Institute for Research in Biomedicine, Faculty of Biomedical Sciences, Università della Svizzera Italiana (USI), Bellinzona, Switzerland., Raneri M; Institute for Research in Biomedicine, Faculty of Biomedical Sciences, Università della Svizzera Italiana (USI), Bellinzona, Switzerland., Guglielmetti S; Department of Biotechnology and Biosciences (BtBs), University of Milano-Bicocca, Milan, Italy.; Department of Food, Environmental and Nutritional Sciences (DeFENS), University of Milan, Milan, Italy., Gargari G; Department of Food, Environmental and Nutritional Sciences (DeFENS), University of Milan, Milan, Italy., Palatella M; Institute for Research in Biomedicine, Faculty of Biomedical Sciences, Università della Svizzera Italiana (USI), Bellinzona, Switzerland., Willers M; Department of Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Hannover, Germany., Fehlhaber B; Department of Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Hannover, Germany., Werlein C; Institute of Pathology, Hannover Medical School, Hannover, Germany., Vogl T; Institute of Immunology, University of Münster, Münster, Germany., Roth J; Institute of Immunology, University of Münster, Münster, Germany., Grassi F; Institute for Research in Biomedicine, Faculty of Biomedical Sciences, Università della Svizzera Italiana (USI), Bellinzona, Switzerland., Viemann D; Department of Pediatrics, University Hospital Würzburg, Würzburg, Germany. Viemann_d@ukw.de.; Department of Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Hannover, Germany. Viemann_d@ukw.de.; Center for Infection Research, University Würzburg, Würzburg, Germany. Viemann_d@ukw.de.; Cluster of Excellence RESIST (EXC 2155), Hannover Medical School, Hannover, Germany. Viemann_d@ukw.de.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Oct 04; Vol. 15 (1), pp. 8623. Date of Electronic Publication: 2024 Oct 04.
DOI: 10.1038/s41467-024-52829-x
Abstrakt: 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
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