Moving from genome-scale to community-scale metabolic models for the human gut microbiome

Abstract

Metabolic models of individual microorganisms or small microbial consortia have become standard research tools in the bioengineering and systems biology fields. However, extending metabolic modelling to diverse microbial communities, such as those in the human gut, remains a practical challenge from both modelling and experimental validation perspectives. In complex communities, metabolic models accounting for community dynamics, or those that consider multiple objectives, may provide optimal predictions over simpler steady-state models, but require a much higher computational cost. Here we describe some of the strengths and limitations of microbial community-scale metabolic models and argue for a robust validation framework for developing personalized, mechanistic and accurate predictions of microbial community metabolic behaviours across environmental contexts. Ultimately, quantitatively accurate microbial community-scale metabolic models could aid in the design and testing of personalized prebiotic, probiotic and dietary interventions that optimize for translationally relevant outcomes.