Modeling microbial cross-feeding at intermediate scale portrays community dynamics and species coexistence

Social interaction between microbes can be described at many levels of details, ranging from the biochemistry of cell-cell interactions to the ecological dynamics of populations. Choosing the best level to model microbial communities without losing generality remains a challenge. Here we propose to model cross-feeding interactions at an intermediate level between genome-scale metabolic models of individual species and consumer-resource models of ecosystems, which is suitable to empirical data. We applied our method to three published examples of multi-strain Escherichia coli communities with increasing complexity consisting of uni-, bi-, and multi-directional cross-feeding of either substitutable metabolic byproducts or essential nutrients. The intermediate-scale model accurately described empirical data and could quantify exchange rates elusive by other means, such as the byproduct secretions, even for a complex community of 14 amino acid auxotrophs. We used the three models to study each community's limits of robustness to perturbations such as variations in resource supply, antibiotic treatments and invasion by other "cheaters" species. Our analysis provides a foundation to quantify cross-feeding interactions from experimental data, and highlights the importance of metabolic exchanges in the dynamics and stability of microbial communities.