ORIGINAL RESEARCH article
Front. Microbiol.
Sec. Microorganisms in Vertebrate Digestive Systems
Volume 16 - 2025 | doi: 10.3389/fmicb.2025.1584041
Integrated analysis of Serum Metabolomics and Fecal Microbiome in Infants with Necrotizing Enterocolitis
Provisionally accepted
- Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
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Background: Necrotizing enterocolitis (NEC), a lethal gastrointestinal disorder in preterm infants, remains poorly understood in its pathology, and early diagnosis are critically limited. Multi-omics approaches present unprecedented opportunities to elucidate NEC pathogenesis and identify clinically translatable biomarkers.: Infants with Bell stage II-III NEC and gestational age-matched controls were enrolled. Serum/stool samples from NEC patients at acute (NEC-D) and recovery (NEC-R) phases, and controls (non-NEC) were collected. Fecal metagenomic sequencing and serum untargeted metabolomic profiling were performed. Clinical parameters were compared. Results: The study comprised seven NEC and seven non-NEC infants. Baseline neonatal characteristics and maternal perinatal parameters showed no significant differences between NEC-D and non-NEC except for markedly lower leukocyte counts in NEC infants. Fecal metagenomics revealed severely diminished alpha diversity in NEC-D versus both non-NEC controls and NEC-R, characterized with lower Chao1 index. NEC-D exhibited elevated Escherichia coli relative abundance alongside reduced Staphylococcus haemolyticus, Staphylococcus aureus, Staphylococcus epidermidis, and Lactobacillus paracasei. Correspondingly, KEGG functional gene analysis demonstrated impaired metabolism in NEC-D. Serum metabolomics identified significantly decreased ornithine, DL-arginine, L-threonine, leucine, and D-proline in NEC-D versus non-NEC. NEC-D also showed lower taurodeoxycholic acid, glycocholic acid, and chenodeoxycholic acid compared to NEC-R. Integrative analysis revealed a positive correlation between the metabolites D-proline and ornithine and the Lactobacillus paracasei, Staphylococcus epidermidis, and Staphylococcus aureus abundance. Conclusions: NEC is characterized by gut microbiota dysbiosis with reduced diversity, altered functional gene expression, and disrupted host-microbiota metabolic crosstalk. The identified serum metabolite-microbiome correlations provide mechanistic insights into NEC pathogenesis and potential diagnostic biomarkers.
Keywords: preterm infant, necrotizing enterocolitis, microbiome, Metabolomics, multi-omics
Received: 28 Feb 2025; Accepted: 23 Apr 2025.
Copyright: © 2025 Lin, He, Kong, Zhu, Li, Tan, Su, Jia and WU. 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:
Chunhong Jia, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
FAN WU, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
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