A mechanistic model of metabolic symbioses in microbes recapitulates experimental data and identifies a continuum of symbiotic interactions.

Microbial symbioses based on nutrient exchange and interdependence are ubiquitous in nature and biotechnologically promising; however, an in-depth mathematical description of their exact underlying dynamics from first principles is still missing. Hence, in this paper a novel mechanistic mathematical model of such a relationship in a continuous chemostat culture is derived. In contrast to preceding works on the topic, only parameters which can be directly measured and understood from biological first principles are used, allowing for a higher degree of mechanistic understanding of the underlying processes compared to previous approaches. The predictive power of the model is validated by demonstrating that it accurately recapitulates both the temporal dynamics as well as the final state of a previously published cross-feeding experiment. The model is then used to examine the influence of the biological traits of the involved organisms on the position and stability of the equilibrium states of the system using bifurcation analyses. It is additionally demonstrated how manipulating the external metabolite concentrations of the system can shift the species interaction on a continuous spectrum ranging from mutualism over commensalism to parasitism. This further reinforces the idea of a continuous spectrum of symbiotic interactions as opposed to static and discrete categories. Finally, the practical implications of the results for the biotechnological application of such microbial consortia are discussed.