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Published on: May 10, 2024
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.
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.
Background:
Early postnatal gut colonization, microbial metabolite production, and immune maturation proceed in parallel. Although disruption has been linked to later allergic disease, cellular immune patterns remain insufficiently defined. Very and extremely preterm infants frequently develop eosinophilia, providing a setting to relate eosinophil dynamics to exposures and gut microbial-metabolic features.
Methods:
We analyzed 15,795 CBC measurements from 734 preterm infants, together with fecal 16S profiling, metabolomics, eosinophil follow-up, and mouse perturbation experiments. Antibiotic and feeding exposures, microbiota, and metabolites were evaluated by longitudinal and integrated analyses; mouse experiments examined antibiotic responses with or without sodium butyrate.
Results:
Eosinophils showed a transient postnatal trajectory, with highest levels at 3-4 weeks. Higher eosinophil levels were associated with greater antibiotic exposure, delayed feeding tolerance, and higher eosinophil counts during the first year of follow-up. During the peak window, eosinophil levels were inversely associated with gut microbial diversity, Clostridium abundance, and fecal short-chain fatty acids, particularly butyrate. In neonatal mice, antibiotics coincided with higher splenic eosinophils and intestinal ILC2/type-2 signatures, whereas sodium butyrate yielded profiles closer to controls.
Conclusion:
Early eosinophil expansion in these infants represents a time-restricted immune trajectory associated with NICU exposures and microbial-metabolic features. Clostridium-butyrate signatures are candidate correlates warranting mechanistic and outcome validation.
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