Aim: During the first days of life, the gut microbial communities and the host immunity develop in a delicate, not yet fully delineated process. Various interferences with normal early gut colonization challenge this process, including surgical delivery, formula feeding and antibiotics. All of these influences are even more relevant in very preterm infants (VPIs), who are additionally exposed to the microbial environment of neonatal intensive care units. Short-term effects of these disturbances on the neonatal microbiome have been previously studied, albeit often under modestly controlled conditions, as have effects of prophylactic countermeasures like probiotics.

Thus, for VPIs, there is a clear need to identify therapeutic options (including specific probiotic formulations) that can support the development of a healthy, eubiotic gut microbiome from infancy through childhood into later life.

Design: 1. Comparative microbiome analysis by deep metagenomic sequencing (performed in a separate workpackage at EMBL, Heidelberg) of the gut microbiome in very preterm infants (VPI) in a subset of the PRIMAL clinical study (n = 120) and their healthy mothers (n = 120) in the presence or absence of antibiotics with or without the use of probiotics during the first year of life.
2. 16S rRNA sequencing of all PRIMAL clinical study fecal samples for lower resolution taxonomical
analysis (will be done at the University Medical Center Mainz), allowing independent validation of discoveries.

Expected outcome:Our project includes in depth investigation of the microbiome, based on the randomized and controlled PRIMAL clinical study and is ideally positioned to provide rationales for novel therapeutic strategies, including the next generation of probiotics.