Dai Kun, Ding Lingli, Yang Xiaomeng, Wang Suqing, Rong Zhihui
School of Nursing, Wuhan University, Wuhan 430071, China.
Tongji Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Microorganisms. 2025 Sep 22;13(9):2213. doi: 10.3390/microorganisms13092213.
Preterm birth remains a significant global health challenge and is strongly associated with heightened risks of long-term neurodevelopmental impairments, including cognitive delays, behavioural disorders, and emotional dysregulation. In recent years, accumulating evidence has underscored the critical role of the gut microbiota in early brain development through the gut-brain axis. In preterm infants, microbial colonisation is frequently delayed or disrupted due to caesarean delivery, perinatal antibiotic exposure, formula feeding, and prolonged stays in neonatal intensive care units (NICUs), all of which contribute to gut dysbiosis during critical periods of neurodevelopment. This review synthesises current knowledge on the sources, temporal patterns, and determinants of gut microbiota colonisation in preterm infants. This review focuses on the gut bacteriome and uses faecal-sample bacteriome sequencing as its primary method of characterisation. We detail five mechanistic pathways that link microbial disturbances to adverse neurodevelopmental outcomes: immune activation and white matter injury, short-chain fatty acids (SCFAs)-mediated neuroprotection, tryptophan-serotonin metabolic signalling, hypothalamic-pituitary-adrenal (HPA) axis modulation, and the integrity of intestinal and blood-brain barriers (BBB). We also critically examine emerging microbiota-targeted interventions-including probiotics, prebiotics, human milk oligosaccharides (HMOs), antibiotic stewardship strategies, skin-to-skin contact (SSC), and faecal microbiota transplantation (FMT)-focusing on their mechanisms of action, translational potential, and associated ethical concerns. Finally, we identify key research gaps, including the scarcity of longitudinal studies, limited functional modelling, and the absence of standardised protocols across clinical settings. A comprehensive understanding of microbial-neurodevelopmental interactions may provide a foundation for the development of targeted, timing-sensitive, and ethically sound interventions aimed at improving neurodevelopmental outcomes in this vulnerable population.
早产仍然是一项重大的全球健康挑战，并且与长期神经发育障碍的高风险密切相关，这些障碍包括认知延迟、行为障碍和情绪调节障碍。近年来，越来越多的证据强调了肠道微生物群通过肠-脑轴在早期大脑发育中的关键作用。在早产儿中，由于剖宫产、围产期抗生素暴露、配方奶喂养以及在新生儿重症监护病房（NICU）的长时间停留，微生物定植常常延迟或中断，所有这些因素都导致了神经发育关键时期的肠道菌群失调。本综述综合了关于早产儿肠道微生物群定植的来源、时间模式和决定因素的现有知识。本综述聚焦于肠道细菌群落，并将粪便样本细菌群落测序作为其主要的表征方法。我们详细阐述了将微生物紊乱与不良神经发育结局联系起来的五条机制途径：免疫激活和白质损伤、短链脂肪酸（SCFA）介导的神经保护、色氨酸-血清素代谢信号传导、下丘脑-垂体-肾上腺（HPA）轴调节以及肠道和血脑屏障（BBB）的完整性。我们还批判性地审视了新兴的针对微生物群的干预措施，包括益生菌、益生元、人乳寡糖（HMO）、抗生素管理策略、皮肤接触（SSC）和粪便微生物群移植（FMT），重点关注它们的作用机制、转化潜力以及相关的伦理问题。最后，我们确定了关键的研究空白，包括纵向研究的稀缺、有限的功能建模以及临床环境中缺乏标准化方案。对微生物与神经发育相互作用的全面理解可能为开发旨在改善这一脆弱人群神经发育结局的有针对性、时机敏感且符合伦理的干预措施提供基础。
