The gut microbiome plays an important role in human health regulation, which can be affected by multiple factors, such as prebiotics/fibre, antibiotics and probiotics. Among them, the vitality of diet's effect on the gut microbiome has been highlighted and focused on due to its long-term regulatory effects on the human gut microbiome. Individual nutrients had been emphasised previously due to their capability to sustain the growth or modulation of the human gut microbiome. However, the physical forms they present to the gut microbiome have been neglected and rarely studied. The physical form may be altered by protein crosslinking, polysaccharides' matrix, and emulsion formation, which show various food matrix structures (liquid, gel, or solid). Therefore, its bioavailability and bioaccessibility may be altered after human digestion, especially when experiencing an impaired/immature digestion system. The weaning infants’ gut model was chosen as a representation for establishing the in vitro digestive and colonic fermentation systems to study the food matrix impact on the human gut microbiome due to the importance of solid food introduction at this stage. INFOGEST had been developed for many years as a mature adult in vitro digestion model. Several infant INFOGEST models have been proposed as well, but no consensus model is being proposed for now. As well as no weaning infant model is proposed. Hence, a modified in vitro digestion and a synthesised in vitro gut microbiome model to represent weaning infants in vivo condition will be utilised to simulate the physiology of weaning infants and show the performance of food matrices for their digestion kinetics, metabolism behaviour, and innate interactions between the nutrients. Comparison between existing and proposed models with the synchronised substrate will be performed to validate the efficiency of weaning infant digestion and gut microbiome model to establish validified models to represent weaning infant’s physiology.