Systems biology of bacteria-host interactions

The aim of systems biology is to use computational methods to gain a complete, systems-level understanding of a cell, organism, or ecosystem. This chapter describes computational systems biology approaches and their applications to human gut microbiome research, with particular focus on constraint-based modeling. At heart of the Constraint-Based Modeling and Analysis (COBRA) approach are accurate, well-structured metabolic reconstructions based on the target organisms' genome sequences. Such genome-scale reconstructions (GENREs) are constructed in a bottom-up manner and describe the target organism's metabolism. The availability of high-quality reconstructions of human metabolism and of other host organisms, enables the computational modeling of host-microbe interactions. Simulating host-microbe interactions is particularly valuable since it could be used to minimize the number of animal experiments. The discussed computational modeling approaches will be valuable tools for studying microbial dysbiosis and its impact on host metabolism. Common approaches for computational modeling include ordinary differential equation (ODE) and kinetic modeling.