Preterm birth affects approximately one in every ten neonates. The clinical outcomes depend on care and management factors, including the birth delivery method and the use of antibiotics. This observational cohort study determined antimicrobial peptides, proteases, metabolomic, and microbiome profiles in fecal samples collected from 20 preterm and nine full-term neonates 48 h after birth. The results show that preterm neonates have increased levels of α-defensins, serine proteases, and matrix metalloproteinases. They also have distinct metabolic signatures characterized by decreased kynurenic acid and increased mevalonate levels. These neonates also exhibit reduced microbial diversity. This study highlights that heightened immune response and proteolytic activity, marked dysbiosis, and reduced short-chain fatty acids within the preterm gastrointestinal tract immediately after birth might predispose neonates to exacerbated gut inflammation. Some of the findings, including the elevated fecal mevalonate levels, are potential biomarkers in neonatology for early identification of metabolic disturbances linked to gut inflammation, emphasizing further studies to explore its association with inflammatory conditions in preterm infants. Inflammatory markers that can predict intestinal disorders are insufficiently characterized in preterm neonates. This study identified antimicrobial peptide responses, proteolytic activity, marked dysbiosis, and reduced short-chain fatty acid production in feces from preterm neonates. These critical differences in inflammatory, metabolomic, and microbial signatures may predispose to exacerbated gut inflammation in preterm neonates. Some inflammatory effectors in feces are potential biomarkers for the early detection of intestinal inflammatory conditions in preterm neonates. This study contributes to understanding the inflammatory conditions in the guts of preterm babies and identifies novel targets for timely diagnosis, interventions, and management practices in neonatal care.
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