肠道微生物群不成熟伴DL内肽酶缺乏与抗生素使用与早产迟发性败血症有关
Gut microbiota immaturity with DL-endopeptidase deficiency links antibiotic use to preterm late-onset sepsis.
摘要(中文译文)
早产儿早期抗生素暴露会增加晚发型败血症（LOS）风险，其机制可能涉及肠道菌群失调。通过分析来自中国、美国和英国早产儿的4,938份纵向粪便样本，我们发现早产儿肠道微生物群发育速度存在差异。发育迟缓与早期抗生素暴露相关LOS风险的超过三分之一有关。细菌DL-内肽酶缺乏是微生物群发育迟缓的标志，并与LOS风险升高相关。补充产DL-内肽酶的屎肠球菌或罗伊氏粘液乳杆菌可通过胞壁酰二肽（MDP）激活NOD2受体，调节巨噬细胞分化和极化，通过诱导圆柱瘤病蛋白（CYLD）抑制过度炎症，并保护新生小鼠免于LOS。一项初步随机对照试验显示，补充罗伊氏粘液乳杆菌可增强早产儿粪便中的NOD2激活。这些发现将微生物群不成熟和DL-内肽酶活性降低与抗生素暴露及LOS风险联系起来，并提示了一个值得进一步验证以推动临床转化的候选生物标志物。
Abstract
Early antibiotic exposure increases late-onset sepsis (LOS) risk in preterm infants, potentially via gut dysbiosis. Analyzing 4,938 longitudinal fecal samples from preterm infants in China, the US, and the UK, we identified a differential pace of gut microbiota development among preterm infants. Delayed maturation correlated with over one-third of LOS risk associated with early antibiotic exposure. Deficiency of a bacterial DL-endopeptidase represented a hallmark of delayed microbiota development and correlated with elevated LOS risk. Supplementation with DL-endopeptidase-producing Enterococcus faecium or Limosilactobacillus reuteri activated the NOD2 receptor via muramyl dipeptide (MDP), regulated macrophage differentiation and polarization, restrained hyperinflammation via cylindromatosis (CYLD) induction, and protected neonatal mice from LOS. A pilot randomized controlled trial showed that L. reuteri supplementation enhanced fecal NOD2 activation in preterm infants. These findings link microbiota immaturity and reduced DL-endopeptidase activity to antibiotic exposure and LOS risk and highlight a candidate biomarker that warrants further validation for clinical translation.
如何引用
AMA
Wei Shen, Huidi Wang, Jiaxuan Wang, Yuan Yuan, Ying Luo, Xirao Chen, et al. Gut microbiota immaturity with DL-endopeptidase deficiency links antibiotic use to preterm late-onset sepsis.. Cell host & microbe. 2026; doi:10.1016/j.chom.2026.02.004.
APA
Wei Shen, Huidi Wang, Jiaxuan Wang, Yuan Yuan, Ying Luo, Xirao Chen, et al (2026). Gut microbiota immaturity with DL-endopeptidase deficiency links antibiotic use to preterm late-onset sepsis.. Cell host & microbe. https://doi.org/10.1016/j.chom.2026.02.004
GB/T 7714
Wei Shen, Huidi Wang, Jiaxuan Wang, Yuan Yuan, Ying Luo, Xirao Chen, et al. Gut microbiota immaturity with DL-endopeptidase deficiency links antibiotic use to preterm late-onset sepsis.[J]. Cell host & microbe, 2026 doi:10.1016/j.chom.2026.02.004.
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