Genome-scale community metabolic modeling of maize root-associated microbiota shows that root exudates stimulate diverse metabolic interactions

Abstract

Microbes play a vital role in plant development, health, and resilience, yet relatively little is known about the specific metabolic mechanisms driving interactions in these host-associated communities. Systems biology models enable a computational approach to understanding metabolic interactions, which can be difficult to pinpoint experimentally; however, these methods cannot yet accommodate the large number of species in natural communities. Synthetic communities (SynComs) provide a more tractable alternative to explore targeted interactions. Here, we investigated metabolite exchange in a seven-member maize root-associated SynCom, specifically accounting for plant host context by designing a customized exudate medium. We constructed metabolic models for each bacterial species and curated them with in vitro phenotyping data to reflect experimentally based carbon uptake potential. Flux balance analysis of individual species demonstrated that integrating phenotype data and changing medium type had substantial impacts on predicted growth rates, which in turn shaped potential interspecies interactions. In silico community growth optimization of the seven-member community model showed that the exudate medium supported a more diverse community composition compared to minimal medium, with predictions of community member abundance closely aligned to literature-derived experimental results. Predicted metabolite exchange in the root exudate environment showed Enterobacter ludwigii as a community hub, and cross-feeding of indole suggested a potential effect of bacterial community interactions on the plant host. Our in silico findings indicate the host plays an important role in structuring microbial interactions and cross-feeding at the metabolic level, underscoring the importance of considering environmental context from both theoretical and experimental perspectives. IMPORTANCETrue understanding of a system is marked by the ability to predict its behavior. The complexity of natural host-microbe systems represents a frontier of knowledge that scientists are working to understand, and elucidating principles of interactions within multi-partite microbial communities remains a challenge in microbial ecology. Synthetic communities provide a tractable starting point for investigating interaction mechanisms, and computational approaches complement laboratory experiments by systematically evaluating multiple possibilities for metabolic pathway processing, thereby allowing us to comprehensively study the interconnected metabolic networks of host-associated microbiota. The model we developed for the seven-member maize root-associated bacterial community presents a step toward predicting plant-microbe behavior, providing hypotheses for future experimental testing and serving as a template for expanding model complexity to more members and other systems.