Aberrant gut-microbiota-immune-brain axis development in premature neonates with brain damage

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. [Display omitted] •Microbiota, immune, and neurophysiological profile of 60 extremely premature infants•Pro-inflammatory T cell response correlates with suppressed electrocortical maturation•γδ T cells have central implications for the pathogenesis of brain injury•Klebsiella overgrowth in the gastrointestinal tract is predictive for brain damage Seki et al. performed a comprehensive, time-resolved analysis of the gut microbiota-immune-brain axis in extremely premature infants. This analysis links early-life microbiome establishment to immunological and neurological development, identifying candidate biomarkers of perinatal brain injury and promising targets for personalized treatments to alleviate, or even prevent, life-long neurological morbidities.