Integrated analysis of serum metabolomics and fecal microbiome in infants with necrotizing enterocolitis
BackgroundNecrotizing 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 t...
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| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2025-06-01
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| Series: | Frontiers in Microbiology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fmicb.2025.1584041/full |
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| Summary: | BackgroundNecrotizing 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.MethodsInfants 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.ResultsThe 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.ConclusionNEC 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. |
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| ISSN: | 1664-302X |