ORIGINAL RESEARCH article
Front. Cell. Infect. Microbiol.
Sec. Intestinal Microbiome
Volume 15 - 2025 | doi: 10.3389/fcimb.2025.1649384
Characterization of Gut Microbiota Signatures in Indian Preterm Infants with Necrotizing Enterocolitis: A Shotgun Metagenomic Approach
Provisionally accepted- Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
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Necrotizing enterocolitis (NEC) is an inflammatory bowel disease that primarily affects preterm infants. Predisposing risk factors for NEC include prematurity, formula feeding, anemia, and sepsis. To date, no studies have investigated the gut microbiota of preterm infants with NEC in India. In the current study, shotgun metagenomic sequencing was performed on fecal samples from premature infants with NEC and healthy preterm infants (n = 24). Sequencing was conducted using the NovaSeq X Plus platform, generating 2 × 150 bp pairedend reads. The infants were matched based on gestational age and postnatal age. The median time to NEC diagnosis was 9 days (range: 1-30 days). Taxonomic analysis revealed a high prevalence of Enterobacteriaceae at the family level, with the genera Klebsiella and Escherichia particularly prominent in neonates with NEC. No statistically significant differences in alpha or beta diversity were observed between stool samples from infants with and without NEC. Linear regression analysis demonstrated that Enterobacteriaceae were significantly more abundant in stool samples from infants with NEC than in those without NEC (q < 0.05). Differential abundance analysis using Linear Discriminant Analysis Effect Size (LEfSe) identified Klebsiella pneumoniae and Escherichia coli as enriched in the gut microbiota of preterm infants with NEC. Functional analysis revealed an increase in genes associated with lipopolysaccharide (LPS) O-antigen, the type IV secretion system (T4SS), the L-rhamnose pathway, quorum sensing, and iron transporters, including ABC transporters, in stool samples from infants with NEC. In conclusion, the high prevalence of Enterobacteriaceae and enrichment of LPS O-antigen and T4SS genes may be associated with NEC in Indian preterm infants.
Keywords: necrotizing enterocolitis, Gut Microbiota, preterm infants, Shotgun metagenomics, LPS O-antigen
Received: 18 Jun 2025; Accepted: 13 Aug 2025.
Copyright: © 2025 Devarajalu, Attri, Kumar, Dutta and Kabeerdoss. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Jayakanthan Kabeerdoss, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
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