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: from the biochemistry of cell-cell interactions to the ecological dynamics of populations. Choosing an appropriate level to model microbial communities without losing generality remains a challenge. Here we show that modeling cross-feeding interactions at an intermediate level between genome-scale metabolic models of individual species and consumer-resource models of ecosystems is suitable to experimental data. We applied our modeling framework to three published examples of multi-strain Escherichia coli communities with increasing complexity: uni-, bi-, and multi-directional cross-feeding of either substitutable metabolic byproducts or essential nutrients. The intermediate-scale model accurately fit empirical data and quantified metabolic exchange rates that are hard to measure experimentally, even for a complex community of 14 amino acid auxotrophies. By studying the conditions of species coexistence, the ecological outcomes of cross-feeding interactions, and each community’s robustness to perturbations, we extracted new quantitative insights from these three published experimental datasets. 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.