How Oxygen and Lactose Metabolism Shape the Infant Gut Microbiota

Nearly immediately after birth, a complex and dynamic ecosystem forms in the human infant gut. The characteristics of this system influence the infant's health in both the short and long term. 2'-FL, the most prevalent prebiotic in most human milk, varies greatly in presence and concentration between individuals. We use a multi-scale spatiotemporal model of the infant colon from birth to three weeks of age to reproduce the effects of variations in nutritional components on the composition and metabolic activity of the microbiota. Using flux balance analysis with molecular crowding on genome-scale metabolic models from the AGORA project, we calculate bacterial fluxes for different locations and time points at a high resolution. The resulting fluxes are integrated together into a model of the ecosystem that feeds back into the flux calculations. The model can give insight and produce predictions for bacterial and metabolic composition of the infant microbiota over time and under different conditions. Our aim is to reach a deeper understanding of the influence that nutrition can have on the development of the infant microbiota. This in turn is the first step towards a comprehensive understanding of the formation of a steady state adult microbial environment.