Lin Zhi-Ying, He Shan-Shan, Mo Zi-Tong, Liao Xiao-Tian, Feng Zhou-Shan, Kong Juan, Zhu Lu, Li Ying, Tan Hui-Yuan, Su Zhi-Wen, Jia Chun-Hong, Wu Fan
Guangzhou Key Laboratory of Neonatal Intestinal Diseases, Department of Neonatology, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, China.
Department of Obstetrics and Gynecology, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, China.
Front Microbiol. 2025 Jun 5;16:1584041. doi: 10.3389/fmicb.2025.1584041. eCollection 2025.
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.
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 relative abundance alongside reduced , , , and . 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 , , and abundance.
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.
坏死性小肠结肠炎（NEC）是一种发生于早产儿的致命性胃肠道疾病，其病理机制仍未完全明确，早期诊断也受到严重限制。多组学方法为阐明NEC发病机制和识别具有临床转化价值的生物标志物提供了前所未有的机遇。
纳入Bell II-III期NEC婴儿及孕周匹配的对照婴儿。收集NEC患者急性期（NEC-D）和恢复期（NEC-R）以及对照（非NEC）的血清/粪便样本。进行粪便宏基因组测序和血清非靶向代谢组学分析。比较临床参数。
该研究纳入7例NEC婴儿和7例非NEC婴儿。除NEC婴儿白细胞计数明显较低外，NEC-D组与非NEC组的基线新生儿特征和母亲围产期参数无显著差异。粪便宏基因组学显示，与非NEC对照和NEC-R相比，NEC-D的α多样性严重降低，特征为Chao1指数较低。NEC-D显示 、 、 、 相对丰度升高而 降低。相应地，KEGG功能基因分析表明NEC-D存在代谢受损。血清代谢组学分析发现，与非NEC相比，NEC-D中鸟氨酸、DL-精氨酸L-苏氨酸、亮氨酸和D-脯氨酸显著降低。与NEC-R相比，NEC-D的牛磺去氧胆酸、甘氨胆酸和鹅去氧胆酸也较低。综合分析显示，代谢物D-脯氨酸和鸟氨酸与 、 、 丰度之间呈正相关。
NEC的特征是肠道微生物群失调，表现为多样性降低、功能基因表达改变以及宿主-微生物群代谢串扰破坏。所确定的血清代谢物-微生物组相关性为NEC发病机制和潜在诊断生物标志物提供了机制性见解。
