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

Author

Listed:
  • Lisa Perruzza

    (Università della Svizzera Italiana (USI)
    Humabs BioMed SA a Subsidiary of Vir Biotechnology Inc.)

  • Julia Heckmann

    (University Hospital Würzburg)

  • Tanja Rezzonico Jost

    (Università della Svizzera Italiana (USI))

  • Matteo Raneri

    (Università della Svizzera Italiana (USI))

  • Simone Guglielmetti

    (University of Milano-Bicocca
    University of Milan)

  • Giorgio Gargari

    (University of Milan)

  • Martina Palatella

    (Università della Svizzera Italiana (USI))

  • Maike Willers

    (Hannover Medical School)

  • Beate Fehlhaber

    (Hannover Medical School)

  • Christopher Werlein

    (Hannover Medical School)

  • Thomas Vogl

    (University of Münster)

  • Johannes Roth

    (University of Münster)

  • Fabio Grassi

    (Università della Svizzera Italiana (USI))

  • Dorothee Viemann

    (University Hospital Würzburg
    Hannover Medical School
    University Würzburg
    Hannover Medical School)

Abstract

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.

Suggested Citation

  • Lisa Perruzza & Julia Heckmann & Tanja Rezzonico Jost & Matteo Raneri & Simone Guglielmetti & Giorgio Gargari & Martina Palatella & Maike Willers & Beate Fehlhaber & Christopher Werlein & Thomas Vogl , 2024. "Postnatal supplementation with alarmins S100a8/a9 ameliorates malnutrition-induced neonate enteropathy in mice," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-52829-x
    DOI: 10.1038/s41467-024-52829-x
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    References listed on IDEAS

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    1. Ruairi C. Robertson & Thaddeus J. Edens & Lynnea Carr & Kuda Mutasa & Ethan K. Gough & Ceri Evans & Hyun Min Geum & Iman Baharmand & Sandeep K. Gill & Robert Ntozini & Laura E. Smith & Bernard Chasekw, 2023. "The gut microbiome and early-life growth in a population with high prevalence of stunting," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    2. Thaddeus S. Stappenbeck & Herbert W. Virgin, 2016. "Accounting for reciprocal host–microbiome interactions in experimental science," Nature, Nature, vol. 534(7606), pages 191-199, June.
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