The premature gut microbiome and the influence on neonatal immunity, brain development and white matter injury - The PreMiBraIn study
Recent advances in neonatal intensive care have dramatically increased the survival rate of extremely premature infants but the number of survivors with severe morbidity and lifelong neurodevelopmental impairment remains high. Perinatal white matter injury is the predominant form of brain injury in premature infants, often leading to adverse outcome. Hypoxic-ischemic events as well as intrauterine and neonatal infection and inflammation have been identified as major risk factors of neonatal brain injury. The fragile gut microbiome of premature infants seems to play an important role in health and disease as distortions of the microbiome occur prior to sepsis and necrotizing enterocolitis. Furthermore, the close link of the gut microbiome to psychiatric and neurological diseases suggests that the microbiome may even influence infant development. Recent studies have underlined the importance of regulatory T cells as well as γδ T cells in brain injury, which can be directly influenced by the gut microbiome. It is therefore likely that an underdeveloped or distorted gut microbiome affects host immune response and may be a risk factor for neurodevelopmental disabilities in extremely premature infants. Therefore, the overarching aim of the PreMiBraIn study is to elucidate the role of the gut-immune-brain axis on neonatal brain injury and its impact on long-term neurodevelopmental outcome of extremely premature infants. This goal will be achieved by state-of-the-art techniques using 16s rRNA gene sequencing of the gut microbiome, holistic analysis of T cell biology using flow cytometry, whole transcriptome analysis and proteomics as well as neurophysiological measurements (aEEG, NIRS, VEP) and cranial MRI of extremely premature infants. Short- and long-term neurological outcome will be investigated using Bayley Scales of Infant Development, Third Edition (BSID-III) at one and two years corrected age, and Kaufmann-Assessment Battery for Children (K-ABC) at five years of age. The prospects of precision medicine targeting the gut-immune-brain axis in extremely premature infants hold the opportunity to improve the overall outcome of these high-risk patients.
This project is funded by an inter-university research grant between the University of Vienna and the Medical University of Vienna.