Control of ecological outcomes through deliberate parameter changes in a model of the gut microbiome

The generalized Lotka-Volterra (gLV) equations are a mathematical proxy for ecological dynamics. We focus on a gLV model of the gut microbiome, in which the evolution of the gut microbial state is determined in part by pairwise interspecies interaction parameters that encode environmentally mediated resource competition between microbes. We develop an in silico method that controls the steady-state outcome of the system by adjusting these interaction parameters. This approach is confined to a bistable region of the gLV model. In this method, a dimensionality reduction technique called steady-state reduction (SSR) is first used to generate a two-dimensional (2D) gLV model that approximates the high-dimensional dynamics on the 2D subspace spanned by the two steady states. Then a bifurcation analysis of the 2D model analytically determines parameter modifications that drive an initial condition to a target steady state. This parameter modification of the reduced 2D model guides parameter modifications of the original high-dimensional model, resulting in a change of steady-state outcome in the high-dimensional model. This control method, called SSR-guided parameter change (SPARC), bypasses the computational challenge of directly determining parameter modifications in the original high-dimensional system. SPARC could guide the development of indirect bacteriotherapies, which seek to change microbial compositions by deliberately modifying gut environmental variables such as gut acidity or macronutrient availability.