Fig. 1.

Simulation of the metabolism of a growing infant from age 0 to 6 months. a The weight and fat mass of a healthy infant were chosen as the initial state of the simulation. Iterative simulations of the infant’s metabolism were performed, in which the current state was used as input to simulate the next state. The simulations were run in a human metabolic model (HMR 2.00) with the intake of metabolites from breast milk as uptake fluxes. The maintenance energy expenditure was calculated from the current body composition, with an additional term for physical activity, which was a function of both age and weight. The objective of the simulation was set to maximize growth, after expending the maintenance energy. Growth was defined as forming the biomass components (fat and lean mass), and the synthesizing energy required. The ratio of fat to total mass in the biomass composition was a function of age. b Simplified representation of the GEM (HMR 2.00) which contains 3800 Genes, 3000 unique metabolites and 8000 reactions out of which 1400 are cofactor dependent. c The weight increments from the simulation were expressed as a growth trajectory and compared with the 5th, 25th, 50th, 75th, and 95th percentile of WHO reference data.³ d The ratio of fat mass to total mass at each time step, compared with the mean and two standard deviations, from a previous study¹⁵