Gut maturation From in vitro to in vivo models, and the impact of early life nutrition

The fundament of lifelong health is built in the first 1000 days of life, from conception up to approximately 2 years of age. Epidemiological studies show that this period is a critical time window for gut maturation, which can influence the susceptibility to disease in both neonatal and adult life. The gut primarily facilitates nutrient supply for the entire body while at the same time it serves as a barrier to protect the body from environmental challenges, ensuring whole body homeostasis. At birth, these functions are not yet fully mature and development continues during the next few years, in close relation with the type of diet. Delayed or impaired gut maturation may on short term lead to food intolerance, gut infections and inflammation, and on long term to various diseases like neurodevelopmental impairment, inflammatory bowel disease and type 2 diabetes.
Aim of this thesis was to study the effect of various factors on early life gut maturation, with the goal to support optimal development and promote lifelong health. The thesis starts with the establishment of a new model to study intestinal epithelial maturation in vitro. We show that fetal intestinal organoids are a valuable in vitro model to study early life intestinal epithelial maturation, including the interactions with food and bacteria/viruses. In the second part of the thesis we studied the impact of early life nutrition on gut maturation, with a specific focus on the impact of thermal treatment during milk processing. Minimal thermal treatment during milk processing promotes dietary tolerance, limits gut inflammation and enhances gut maturation in vivo in immature piglets, compared with more extensive heating. The findings of this thesis contribute to the progress of early life gut maturation research and to the optimization of early life infant nutrition.