Objective Necrotising enterocolitis (NEC) is a devastating intestinal disease primarily affecting preterm infants. The underlying mechanisms are poorly understood: mother’s own breast milk (MOM) is protective, possibly relating to human milk oligosaccharide (HMO) and infant gut microbiome interplay. We investigated the interaction between HMO profiles and infant gut microbiome development and its association with NEC. Design We performed HMO profiling of MOM in a large cohort of infants with NEC (n=33) with matched controls (n=37). In a subset of 48 infants (14 with NEC), we also performed longitudinal metagenomic sequencing of infant stool (n=644). Results Concentration of a single HMO, disialyllacto-N-tetraose (DSLNT), was significantly lower in MOM received by infants with NEC compared with controls. A MOM threshold level of 241 nmol/mL had a sensitivity and specificity of 0.9 for NEC. Metagenomic sequencing before NEC onset showed significantly lower relative abundance of Bifidobacterium longum and higher relative abundance of Enterobacter cloacae in infants with NEC. Longitudinal development of the microbiome was also impacted by low MOM DSLNT associated with reduced transition into preterm gut community types dominated by Bifidobacterium spp and typically observed in older infants. Random forest analysis combining HMO and metagenome data before disease accurately classified 87.5% of infants as healthy or having NEC. Conclusion These results demonstrate the importance of HMOs and gut microbiome in preterm infant health and disease. The findings offer potential targets for biomarker development, disease risk stratification and novel avenues for supplements that may prevent life-threatening disease. Data are available in a public, open access repository. All sequencing data generated and analysed in this study have been deposited in the European Nucleotide Archive under study accession number PRJEB39610. The metagenomic data are publically available and can be accessed online (). HMO data are avilable upon request.

中文翻译：

---

早产儿的人乳寡糖 DSLNT 和肠道微生物组预测坏死性小肠结肠炎

目的 坏死性小肠结肠炎（NEC）是一种主要影响早产儿的破坏性肠道疾病。其潜在机制知之甚少：母亲自己的母乳 (MOM) 具有保护作用，可能与人乳寡糖 (HMO) 和婴儿肠道微生物组的相互作用有关。我们研究了 HMO 谱与婴儿肠道微生物组发育之间的相互作用及其与 NEC 的关联。设计 我们对一大群 NEC (n=33) 婴儿和匹配对照 (n=37) 进行了 MOM 的 HMO 分析。在 48 名婴儿（14 名 NEC）中，我们还对婴儿粪便进行了纵向宏基因组测序（n=644）。结果 与对照组相比，NEC 婴儿接受的 MOM 中单一 HMO、二唾液酸乳-N-四糖 (DSLNT) 的浓度显着降低。241 nmol/mL 的 MOM 阈值水平对 NEC 的敏感性和特异性为 0.9。NEC 发病前的宏基因组测序显示 NEC 婴儿的长双歧杆菌相对丰度显着降低，阴沟肠杆菌相对丰度显着升高。微生物组的纵向发育也受到低 MOM DSLNT 的影响，这与减少向以双歧杆菌为主的早产肠道群落类型的转变有关，通常在较大的婴儿中观察到。结合疾病前 HMO 和宏基因组数据的随机森林分析准确地将 87.5% 的婴儿分类为健康或患有 NEC。结论 这些结果证明了 HMO 和肠道微生物组在早产儿健康和疾病中的重要性。这些发现为生物标志物的开发提供了潜在的目标，疾病风险分层和可能预防危及生命疾病的补充剂的新途径。数据可在公共、开放访问的存储库中获得。本研究中生成和分析的所有测序数据均已保存在欧洲核苷酸档案中，研究登录号为 PRJEB39610。宏基因组数据是公开的，可以在线访问（）。HMO 数据可应要求提供。