Neonatal intensive care unit exposures reprogram microbiome-metabolome trajectories and modulate host calprotectin in

Yihuang Huang1, Luyang Hong1,2, Shujuan Li1

  • 1Department of Neonatology, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China.

Insights

Antibiotics in the NICU disrupt preterm infant gut microbes and metabolism, impacting immune development. Breast milk offers some protection, highlighting the role of anaerobes and polyamines in gut health.

Area of Science:

  • Microbiology
  • Immunology
  • Neonatal Medicine

Background:

  • Early gut microbiota is crucial for immune development and preventing diseases like necrotizing enterocolitis (NEC) and sepsis.
  • Preterm infants in the NICU face disruptions to gut microbiota development due to various exposures.

Purpose of the Study:

  • To investigate the impact of NICU exposures on the gut microbiota, metabolism, and immune responses in preterm infants.
  • To identify key microbial and metabolic factors mediating the effects of NICU interventions on infant immunity.

Main Methods:

  • Longitudinal multi-omics study of 186 preterm infants.
  • Analysis of 1153 stool samples using quantitative microbial profiling, untargeted metabolomics, and calprotectin levels.
  • Mediation analysis to identify key drivers of observed effects.

Main Results:

  • Antibiotic exposure reduced anaerobic colonization and microbial diversity in a dose-dependent manner; breast milk mitigated this effect.
  • Gut metabolome alterations, particularly in polyamine metabolism, correlated with microbial changes and antibiotic exposure.
  • Host calprotectin levels showed a biphasic pattern linked to microbial diversity and polyamine metabolites, with anaerobe suppression and polyamine depletion mediating antibiotic effects.

Conclusions:

  • NICU interventions, especially antibiotics, significantly alter the preterm gut ecosystem and immune responses.
  • Anaerobic bacteria and polyamine metabolism are critical mediators linking gut microbial ecology to immune maturation in early life.

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