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Updated: Jun 13, 2025
A Neonatal BALB/c Mouse Model of Necrotizing Enterocolitis
Published on: November 30, 2021
Postnatal supplementation with alarmins S100a8/a9 ameliorates malnutrition-induced neonate enteropathy in mice
Lisa Perruzza1,2, Julia Heckmann3, Tanja Rezzonico Jost4
1Institute for Research in Biomedicine, Faculty of Biomedical Sciences, Università della Svizzera Italiana (USI), Bellinzona, Switzerland. lperruzza@vir.bio.
Insights
Maternal malnutrition causes lasting gut inflammation in offspring, impacting gut immunity and microbiota. Supplementing S100a8 in newborns can prevent these effects and protect against bowel diseases.
Area of Science:
- Immunology
- Gastroenterology
- Nutritional Science
Background:
- Maternal malnutrition's impact on child health is unclear, despite its link to childhood mortality.
- Environmental enteropathy in malnourished children is thought to stem from pathogen exposure and dysbiosis.
- Previous research suggested maternal malnutrition doesn't alter breast milk composition.
Purpose of the Study:
- To investigate the effects of maternal malnutrition on offspring gut health in a murine model.
- To identify mechanisms underlying gut dysfunction in offspring of malnourished mothers.
- To explore S100a8/a9 as a potential therapeutic target.
Main Methods:
- Utilized a murine model of maternal malnutrition.
- Analyzed offspring gut inflammation, immune cell influx (neutrophils), and microbiota composition (Enterobacteriaceae).
- Assessed S100a8/a9 levels in breast milk and offspring intestines.
- Administered S100a8 supplementation to neonates from malnourished mothers.
Main Results:
- Maternal malnutrition induced persistent gut inflammation and dysfunction in offspring, characterized by neutrophil influx and Enterobacteriaceae expansion.
- Offspring of malnourished mothers exhibited deficient S100a8/a9 in breast milk and intestines.
- S100a8 supplementation in neonates prevented aberrant gut immune development and microbiota colonization.
- Supplemented offspring showed lifelong protection against enteric infections and bowel diseases.
Conclusions:
- Maternal malnutrition imprints offspring gut immunity and microbiota, leading to long-term dysfunction.
- S100a8/a9 deficiency in breast milk is a key factor in this process.
- Postnatal S100a8 supplementation is a promising strategy to mitigate the detrimental effects of maternal malnutrition on infant gut health.
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.
