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| Item Type: | Preprint |
|---|---|
| Title: | Enteral S100A8 supplementation restores neonatal immune competence and protects against bacterial sepsis |
| Creators: |
Heckmann, Julia  ORCID: https://orcid.org/0000-0002-7173-0954, Arslan, Berkan, Richter, Maximilian, Pirr, Sabine, Forslund, Sofia K. ORCID: https://orcid.org/0000-0003-4285-6993, Härtel, Christoph, Roth, Johannes, Vogl, Thomas and Viemann, Dorothee
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| Abstract: | Despite advances in antimicrobial therapy, host-directed treatments for neonatal sepsis remain limited. S100A8/A9 alarmins regulate neonatal inflammatory responses, but preterm infants experience reduced perinatal S100A8/A9 exposure. Here, we investigated whether postnatal transfer of S100A8/A9 via foster milk or enteral supplementation protects against Gram-positive and Gram-negative neonatal sepsis.In clinically relevant Staphylococcus aureus and Escherichia coli sepsis models, reduced enteral S100A8/A9 supply via breast milk aggravated morbidity and inflammatory responses in otherwise S100A8/A9-competent neonates, whereas additional loss of endogenous S100A8/A9 competence resulted in markedly increased mortality. Foster milk-mediated transfer of S100A8/A9 partially, and a single enteral dose of the S100A8 homodimer after birth fully, restored survival and restrained inflammatory hyperresponsiveness. In E. coli sepsis, S100A8 supplementation additionally reduced systemic bacterial dissemination. Notably, supplementation remained protective after infection onset, supporting enteral S100A8 supplementation as a preventive and therapeutic strategy for neonates with limited perinatal S100A8/A9 exposure, including preterm infants. |
| Keywords: | Neonate, Sepsis, S100A9, Calprotectin, Nutritional Supplementation, Prevention, Therapy, Staphylococcus Aureus, Escherichia Coli, Animals, Mice |
| Source: | SSRN |
| Publisher: | Elsevier |
| Article Number: | 7262905 |
| Date: | 2026 |
| Official Publication: | https://doi.org/10.2139/ssrn.7262905 |
| Related to: |
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