The project led by Gdansk University of Technology will be the first of this scale international, cooperative study of the effect of human milk (HM) structure on the release of nutrients during digestion. We hypothesise that the differences in the (bio)chemical composition of the HM from women that give birth at term vs prematurely, as well as the HM from different stages of lactation (i.e., colostrum vs mature milk) will affect both, the colloidal behaviour of the milk under the infant GI conditions, and the digestibility of major macronutrients in the milk. We will test the hypothesis by involving four different types of HM (n≥30 each) in this project: the colostrum and the mature milk obtained from mothers of preterm infants, as well as the colostrum and the mature milk from mothers of full-term infants. After initial characterisation, the HMs will be subjected to in vitro infant digestion conditions involving the mechanistic aspects of (i) the gastric phase separation and (ii) the dynamic transition of digesta into the small intestine. Finally, the GI fate of the HMs will be monitored by in-depth, state-of-the-art proteomics, lipidomics, oligosaccharide analysis, etc. to identify and explain any digestion time-dependent differences between the four types of HMs. All data will undergo a thorough statistical analysis. Mathematical modelling will be used to find relationship between variables and parameters. By using the contrasting types of real HM and by applying the physiologically relevant semi-dynamic model of infant digestion, we aim to deliver, for the first time, robust scientific data on how the lactation stage can influence the HM digestion and nutrient bioaccessibility in infants born at term and prematurely. Apart from revealing fundamental aspects the HM digestion patterns that may well-reflect physiological conditions, we will also test the GI behaviour of selected infant formulas. This is in order to emphasise any differences related to the behaviour of HM. This is also to produce a comprehensive scientific evidence that would support any future design of such nutritional supplements of HM for feeding preterm and full-term infants at different stages of their early lives.