Early-life microbiota direct an epithelial S100 program required for neonatal immunity.

Early-life microbiota induce epithelial S100A9 expression, which is essential for neonatal immunity, as shown by increased infection susceptibility in knockout mice.

• Why it matters: Understanding how neonatal immune responses develop is crucial because early-life immunity differs from adult responses, and gaps remain in knowledge about underlying mechanisms that protect newborns from infections.
• What they did: The study examined neonatal mice, measuring S100A8/A9 levels, microbiota colonization, and epithelial cell responses, including knockout models and probiotic interventions, to elucidate microbiota-driven immune programming.
• The result: Microbiota-induced epithelial S100A9 expression protects neonates from sepsis, and probiotic bacteria like Lactobacillus, along with indole-3-lactic acid, can prime this defense pathway, offering potential strategies to prevent neonatal infections.