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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Frontiers Media S.A.
2025-06-01
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmicb.2025.1584041/full |
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| author | Zhi-ying Lin Zhi-ying Lin Shan-shan He Zi-tong Mo Xiao-tian Liao Zhou-shan Feng Juan Kong Lu Zhu Ying Li Hui-yuan Tan Zhi-wen Su Chun-hong Jia Chun-hong Jia Fan Wu Fan Wu |
| author_facet | Zhi-ying Lin Zhi-ying Lin Shan-shan He Zi-tong Mo Xiao-tian Liao Zhou-shan Feng Juan Kong Lu Zhu Ying Li Hui-yuan Tan Zhi-wen Su Chun-hong Jia Chun-hong Jia Fan Wu Fan Wu |
| author_sort | Zhi-ying Lin |
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| description | 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. |
| format | Article |
| id | doaj-art-3cf286afd0e749b8b22f63fd4b38fb30 |
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| language | English |
| publishDate | 2025-06-01 |
| publisher | Frontiers Media S.A. |
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| spelling | doaj-art-3cf286afd0e749b8b22f63fd4b38fb302025-08-20T02:03:19ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2025-06-011610.3389/fmicb.2025.15840411584041Integrated analysis of serum metabolomics and fecal microbiome in infants with necrotizing enterocolitisZhi-ying Lin0Zhi-ying Lin1Shan-shan He2Zi-tong Mo3Xiao-tian Liao4Zhou-shan Feng5Juan Kong6Lu Zhu7Ying Li8Hui-yuan Tan9Zhi-wen Su10Chun-hong Jia11Chun-hong Jia12Fan Wu13Fan Wu14Guangzhou Key Laboratory of Neonatal Intestinal Diseases, Department of Neonatology, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, ChinaDepartment of Obstetrics and Gynecology, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, ChinaGuangzhou Key Laboratory of Neonatal Intestinal Diseases, Department of Neonatology, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, ChinaGuangzhou Key Laboratory of Neonatal Intestinal Diseases, Department of Neonatology, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, ChinaGuangzhou Key Laboratory of Neonatal Intestinal Diseases, Department of Neonatology, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, ChinaGuangzhou Key Laboratory of Neonatal Intestinal Diseases, Department of Neonatology, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, ChinaGuangzhou Key Laboratory of Neonatal Intestinal Diseases, Department of Neonatology, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, ChinaGuangzhou Key Laboratory of Neonatal Intestinal Diseases, Department of Neonatology, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, ChinaGuangzhou Key Laboratory of Neonatal Intestinal Diseases, Department of Neonatology, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, ChinaGuangzhou Key Laboratory of Neonatal Intestinal Diseases, Department of Neonatology, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, ChinaGuangzhou Key Laboratory of Neonatal Intestinal Diseases, Department of Neonatology, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, ChinaGuangzhou Key Laboratory of Neonatal Intestinal Diseases, Department of Neonatology, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Major Obstetric Diseases, Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, Guangzhou, ChinaGuangzhou Key Laboratory of Neonatal Intestinal Diseases, Department of Neonatology, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, ChinaDepartment of Obstetrics and Gynecology, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, ChinaBackgroundNecrotizing 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.https://www.frontiersin.org/articles/10.3389/fmicb.2025.1584041/fullpreterm infantnecrotizing enterocolitismicrobiomemetabolomicsmulti-omics |
| spellingShingle | Zhi-ying Lin Zhi-ying Lin Shan-shan He Zi-tong Mo Xiao-tian Liao Zhou-shan Feng Juan Kong Lu Zhu Ying Li Hui-yuan Tan Zhi-wen Su Chun-hong Jia Chun-hong Jia Fan Wu Fan Wu Integrated analysis of serum metabolomics and fecal microbiome in infants with necrotizing enterocolitis Frontiers in Microbiology preterm infant necrotizing enterocolitis microbiome metabolomics multi-omics |
| title | Integrated analysis of serum metabolomics and fecal microbiome in infants with necrotizing enterocolitis |
| title_full | Integrated analysis of serum metabolomics and fecal microbiome in infants with necrotizing enterocolitis |
| title_fullStr | Integrated analysis of serum metabolomics and fecal microbiome in infants with necrotizing enterocolitis |
| title_full_unstemmed | Integrated analysis of serum metabolomics and fecal microbiome in infants with necrotizing enterocolitis |
| title_short | Integrated analysis of serum metabolomics and fecal microbiome in infants with necrotizing enterocolitis |
| title_sort | integrated analysis of serum metabolomics and fecal microbiome in infants with necrotizing enterocolitis |
| topic | preterm infant necrotizing enterocolitis microbiome metabolomics multi-omics |
| url | https://www.frontiersin.org/articles/10.3389/fmicb.2025.1584041/full |
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