Computer-guided design of optimal microbial consortia for immune system modulation

Manipulation of the gut microbiota holds great promise for the treatment of diseases. However, a major challenge is the identification of therapeutically potent microbial consortia that colonize the host effectively while maximizing immunologic outcome. Here, we propose a novel workflow to select optimal immune-inducing consortia from microbiome compositicon and immune effectors measurements. Using published and newly generated microbial and regulatory T-cell (T(reg)) data from germ-free mice, we estimate the contributions of twelve Clostridia strains with known immune-modulating effect to T(reg) induction. Combining this with a longitudinal data-constrained ecological model, we predict the ability of every attainable and ecologically stable subconsortium in promoting T(reg) activation and rank them by the T(reg) Induction Score (TrIS). Experimental validation of selected consortia indicates a strong and statistically significant correlation between predicted TrIS and measured T(reg). We argue that computational indexes, such as the TrIS, are valuable tools for the systematic selection of immune-modulating bacteriotherapeutics.