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Microbes, metabolites, and inflammation: mapping the early neonatal intestinal landscape

Pediatric Research volume 98, pages 31–33 (2025)Cite this article

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Necrotizing enterocolitis (NEC) remains a significant source of morbidity and mortality in preterm infants. Preventive strategies such as the use of breast milk and probiotics have contributed to a relative decline in NEC incidence over the past two decades.1 However, developmental immaturity of the preterm infant and the complexity of intestinal adaptation in neonates, makes identifying early alterations in metabolic, inflammatory, and microbiome pathways that portend gastrointestinal inflammation challenging. This limits our ability to predict diseases such as NEC in preterm infants reliably.2,3 Advances in “omics” technologies evaluating the metabolomic, proteomic, genomic, and microbiota signatures along with machine learning offer promising avenues for revealing early signatures of gut inflammation and identifying infants at risk of severe intestinal inflammatory disease such as NEC.4 In this context, the study by Hannawayya R et al. in the journal is timely, as it seeks to identify inflammatory, metabolomic, and microbiome signatures associated with gut inflammation.5

Hannawayya et al. performed 16S rRNA sequencing and semi-targeted metabolomics in 29 neonates (20 preterm and nine full-term) to evaluate the first fecal sample within 48 h of birth.5 In comparison to term infants, they show decreased bacterial diversity and kynurenic acid, increased levels of antimicrobial peptides (α-defensins), serine proteases, and matrix metalloproteinases (MMPs) in preterm neonates, indicating a dysmature inflammatory gastrointestinal milieu (Table 1). Instead of analyzing results in the context of a distinct phenotype such as NEC, the authors attempt to define early (<3 days of life) differences in stool metabolomic, immune, and microbiota signatures in preterm and term neonates. This approach contrasts with other studies that regard healthy preterm infants as controls in comparison to those who develop gastrointestinal diseases.6 The results from Hannawayya et al. underscore that prematurity, even without complications, is characterized by metabolic, immune, and microbiota signatures representing a heightened inflammatory response.

Table 1 Summary of salient biomarkers in meconium stool samples and their relationships to prematurity, antibiotics, and birth route in the Hannawayya R et al. study.
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Acknowledgements

V.S. effort is partly supported by NIH (1R01DK139636).

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Authors and Affiliations

  1. Division of Neonatology, Baylor College of Medicine, Texas Children’s Hospital, Houston, TX, USA

    Muralidhar H. Premkumar

  2. Division of Neonatology, Children’s Mercy Kansas City, Kansas City, MO, USA

    Lovya George & Venkatesh Sampath

  3. School of Medicine, University of Missouri Kansas City, Kansas City, MO, USA

    Venkatesh Sampath

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  2. Lovya George
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Correspondence to Venkatesh Sampath.

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Premkumar, M.H., George, L. & Sampath, V. Microbes, metabolites, and inflammation: mapping the early neonatal intestinal landscape. Pediatr Res 98, 31–33 (2025). https://doi.org/10.1038/s41390-025-04016-x

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