Early postnatal eosinophil expansion associates with gut microbial-metabolic features and type 2 immunity in preterm

Huiyu Chen1, Yihuang Huang1, Luyang Hong1

  • 1Department of Neonatology, Children's Hospital of Fudan University, National Children's Medical Center; Shanghai 201102, China; NHC Key Laboratory of Neonatal Diseases, Fudan University; Shanghai 201102, China.

Mucosal Immunology
|July 13, 2026
PubMed

Insights

Early eosinophil expansion in preterm infants is linked to NICU exposures and gut microbes. Specific gut bacteria and butyrate may influence this immune response, suggesting targets for future research.

Area of Science:

  • Neonatal immunology
  • Microbiome research
  • Preterm infant health

Background:

  • Gut colonization, microbial metabolite production, and immune maturation are parallel processes in early life.
  • Disruptions in these processes are linked to later allergic diseases, but cellular immune patterns are not well understood.
  • Eosinophilia is common in preterm infants, offering a model to study immune responses related to exposures and gut microbial-metabolomic features.

Purpose of the Study:

  • To investigate the dynamics of eosinophil counts in preterm infants.
  • To correlate eosinophil trajectories with neonatal intensive care unit (NICU) exposures, gut microbiota, and metabolites.
  • To explore the role of specific microbial metabolites, like butyrate, in modulating immune responses.

Main Methods:

  • Analysis of 15,795 complete blood count (CBC) measurements from 734 preterm infants.
  • Fecal 16S rRNA gene sequencing for microbiota profiling and untargeted metabolomics.
  • Longitudinal and integrated analyses of antibiotic and feeding exposures, microbiota, and metabolites, including mouse perturbation experiments.

Main Results:

  • Eosinophils exhibited a transient postnatal peak around 3-4 weeks.
  • Higher eosinophil levels correlated with increased antibiotic exposure, delayed feeding tolerance, and persistent eosinophilia.
  • Peak eosinophil levels were inversely associated with gut microbial diversity, Clostridium abundance, and fecal short-chain fatty acids, especially butyrate.
  • Antibiotics in neonatal mice increased splenic eosinophils and type-2 immune signatures, while sodium butyrate administration modulated these responses.

Conclusions:

  • Early eosinophil expansion in preterm infants is a time-restricted immune trajectory influenced by NICU exposures and gut microbial-metabolic profiles.
  • Clostridium-butyrate signatures are identified as potential correlates of eosinophil dynamics.
  • Further mechanistic studies and outcome validation are warranted to confirm the role of these signatures.
Abstract

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