In the recent past, RG Viemann and RG Hansen contributed to the paradigm shift that a specific inflammatory programming of systemic innate immunity at birth does not reflect infection but actually is a protective S100-alarmin-mediated state (Austermann et al., 2014; Heinemann et al., 2017; Ulas et al., 2017; Pirr et al., 2017; Bickes et al., 2019). Therefore, traditionally used biomarkers and risk criteria need to be scrutinized when evaluating preterm infants. Moreover, RG Viemann and others showed in preterm babies that gut dysbiosis precedes late-onset sepsis and necrotizing enterocolitis (Graspeuntner et al., 2018). RG Hühn demonstrated that the neonatal phase is critical for the stable imprinting of tolerogenic properties in mesenteric lymph node stromal cells by microbiota (Pezoldt et al. 2018). RG Strowig focused on the composition of microbiota and revealed that specific microbial communities can initiate inflammation and modulate the host’s ability to produce anti-bacterial effector cytokines (Thiemann et al., 2017; Roy et al., 2017). Within RESIST we combine our expertise and jointly continue the work on how the newly developing microbiota in preterm infants contributes to the age-dependent programming of innate and adaptive immunity and related susceptibility towards sepsis and respiratory infections. For this purpose we use amongst others data from the “Priming Immunity at the beginning of Life” (PRIMAL) cohort.