Premature infants are at substantial risk for suffering from perinatal white matter injury. Though the gut microbiota has been implicated in early-life development, a detailed understanding of the gut-microbiota-immune-brain axis in premature neonates is lacking. Here, we profiled the gut microbiota, immunological, and neurophysiological development of 60 extremely premature infants, which received standard hospital care including antibiotics and probiotics. We found that maturation of electrocortical activity is suppressed in infants with severe brain damage. This is accompanied by elevated γδ T cell levels and increased T cell secretion of vascular endothelial growth factor and reduced secretion of neuroprotectants. Notably, Klebsiella overgrowth in the gut is highly predictive for brain damage and is associated with a pro-inflammatory immunological tone. These results suggest that aberrant development of the gut-microbiota-immune-brain axis may drive or exacerbate brain injury in extremely premature neonates and represents a promising target for novel intervention strategies.

早产儿遭受围产期白质损伤的风险很大。尽管肠道微生物群与生命早期发育有关，但缺乏对早产新生儿肠道-微生物-免疫-脑轴的详细了解。在这里，我们分析了 60 名极早产儿的肠道微生物群、免疫学和神经生理学发育情况，这些婴儿接受了包括抗生素和益生菌在内的标准医院护理。我们发现严重脑损伤婴儿的皮质电活动成熟受到抑制。这伴随着升高的 γδ T 细胞水平和血管内皮生长因子的 T 细胞分泌增加和神经保护剂的分泌减少。值得注意的是，克雷伯氏菌肠道中的过度生长对脑损伤具有高度预测性，并且与促炎免疫基调有关。这些结果表明，肠道-微生物群-免疫-脑轴的异常发展可能会驱动或加剧极早产儿的脑损伤，并代表了新干预策略的有希望的目标。