Metabolic models of human gut microbiota Advances and challenges

The human gut is a complex ecosystem consisting of hundreds of microbial species interacting with each other and with the human host. Mathematical models of the gut microbiome integrate our knowledge of this system and help to formulate hypotheses to explain observations. The generalized Lotka-Volterra model has been widely used for this purpose, but it does not describe interaction mechanisms and thus does not account for metabolic flexibility. Recently, models that explicitly describe gut microbial metabolite produc-tion and consumption have become popular. These models have been used to investigate the factors that shape gut microbial composition and to link specific gut microorganisms to changes in metabolite concen-trations found in diseases. Here, we review how such models are built and what we have learned so far from their application to human gut microbiome data. In addition, we discuss current challenges of these models and how these can be addressed in the future.