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 and immunological and neurophysiological development of 60 extremely premature infants during hospitalization. We found that maturation of electrocortical activity was suppressed in infants with severe brain damage. This was accompanied by elevated gamma delta T cell levels as well as increased T cell secretion of vascular endothelial growth factor and reduced secretion of neuroprotectants. Notably, Klebsiella overgrowth in the gut was highly predictive for brain damage, and was 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. Sequencing was performed at the Joint Microbiome Facility of the Medical University of Vienna and the University of Vienna under the project ID JMF-1906-2.