{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T23:53:02Z","timestamp":1791417182122,"version":"4.3.3"},"reference-count":30,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,6,5]],"date-time":"2025-06-05T00:00:00Z","timestamp":1749081600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>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 <jats:italic>Escherichia coli<\/jats:italic> relative abundance alongside reduced <jats:italic>Staphylococcus haemolyticus<\/jats:italic>, <jats:italic>Staphylococcus aureus<\/jats:italic>, <jats:italic>Staphylococcus epidermidis<\/jats:italic>, and <jats:italic>Lactobacillus paracasei<\/jats:italic>. 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 <jats:italic>Lactobacillus paracasei<\/jats:italic>, <jats:italic>Staphylococcus epidermidis<\/jats:italic>, and <jats:italic>Staphylococcus aureus<\/jats:italic> abundance.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmicb.2025.1584041","type":"journal-article","created":{"date-parts":[[2025,6,5]],"date-time":"2025-06-05T05:29:44Z","timestamp":1749101384000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Integrated analysis of serum metabolomics and fecal microbiome in infants with necrotizing enterocolitis"],"prefix":"10.3389","volume":"16","author":[{"given":"Zhi-ying","family":"Lin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shan-shan","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zi-tong","family":"Mo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-tian","family":"Liao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhou-shan","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Kong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui-yuan","family":"Tan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi-wen","family":"Su","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun-hong","family":"Jia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,6,5]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"8","DOI":"10.3389\/fped.2020.602255","article-title":"Emerging biomarkers for prediction and early diagnosis of necrotizing enterocolitis in the era of metabolomics and proteomics","volume":"8","author":"Agakidou","year":"2020","journal-title":"Front. 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