The immature preterm intestine under pressure Microbiome ecology and inflammation resolution

Preterm birth exposes the immature intestine to profound environmental stress during a critical window of development. Extremely preterm infants frequently require intensive care, antibiotic treatment, and modified feeding strategies, all of which influence early microbial colonization. At the same time, the intestinal barrier and immune system are incompletely developed, increasing vulnerability to inflammatory diseases such as necrotizing enterocolitis. Understanding how clinical exposures interact with microbiome development and epithelial resilience is essential to improve outcomes in this population.
This thesis investigates the ecology of the preterm gut microbiome and mechanisms of inflammation resolution from both clinical and experimental perspectives. First, a systematic review synthesizes current evidence on feeding type and microbiome composition in preterm infants, highlighting heterogeneity in study design and the need for confounder-aware analyses. Two multicenter clinical studies then examine associations between donor human milk, mother’s own milk, clinical characteristics, and microbial community structure in extremely preterm infants, as well as microbiome associations within necrotizing enterocolitis. Finally, an experimental organoid model evaluates the effects of specialized pro-resolving mediators on epithelial repair and inflammatory responses in early-life intestine.
Together, these studies provide a context-dependent framework in which clinical exposures are associated with shifts in microbial composition and epithelial repair capacity. The findings emphasize the importance of integrating microbial ecology with host biology to better understand vulnerability and resilience in the immature preterm intestine.