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: 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, Fan Wu
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Language:English
Published: Frontiers Media S.A. 2025-06-01
Series:Frontiers in Microbiology
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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
collection DOAJ
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.
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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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