Mucosal Immunol. 2026 Jul 13:100383. doi: 10.1016/j.mucimm.2026.100383. Online ahead of print.
ABSTRACT
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.
PMID:42442612 | DOI:10.1016/j.mucimm.2026.100383