Coarse-Grained Model of Serial Dilution Dynamics in Synthetic Human Gut Microbiome

Abstract

Many microbial communities in nature are complex, with hundreds of coexisting strains and the resources they consume. We currently lack the ability to assemble and manipulate such communities in a predictable manner in the lab. Here, we take a first step in this direction by introducing and studying a simplified consumer resource model of such complex communities in serial dilution experiments. The main assumption of our model is that during the growth phase of the cycle, strains share resources and produce metabolic byproducts in proportion to their average abundances and strain-specific consumption/production fluxes. We fit the model to describe serial dilution experiments in hCom2, a defined synthetic human gut microbiome with a steady-state diversity of 63 species growing on a rich media, using consumption and production fluxes inferred from metabolomics experiments. The model predicts serial dilution dynamics reasonably well, with a correlation coefficient between predicted and observed strain abundances as high as 0.8. We applied our model to: (i) calculate steady-state abundances of leave-one-out communities and use these results to infer the interaction network between strains; (ii) explore direct and indirect interactions between strains and resources by increasing concentrations of individual resources and monitoring changes in strain abundances; (iii) construct a resource supplementation protocol to maximally equalize steady-state strain abundances.