Therefore, the overarching aim of the PreMiBraIn study is to elucidate the role of the gutimmune-brain axis on neonatal brain injury and its impact on long-term neurodevelopmental outcome of extremely premature infants. The study cohort will consist of a total of 50-60 extremely premature infants with a gestational age < 28 weeks and birth weight < 1000 grams. We seek to characterize the orchestrated dynamics of the maturation of the gut microbiome and the subsequent impact on maturation of innate and adaptive immune mechanisms as well as neurophysiological maturation and neurodevelopmental outcome. Furthermore, we will assess the value of the microbiome as a prognostic indicator for neonatal brain injury as well as short- and 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 (amplitude-integrated EEG, near-infrared spectroscopy, visual evoked potentials) and cranial MRI of extremely premature infants. Short- and long-term neurological outcome will be investigated using Bayley Scales of Infant Development, Third Edition at one and two years corrected age, and Kaufmann-Assessment Battery for Children at five years of age. We expect to find microbiome signatures that are predictive for later neurodevelopmental disabilities which may then be used for early screening and intervention and may suggest personalized therapeutic options. 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.