A systems biology approach to studying the role of microbes in human health

Host–microbe interactions play a crucial role in human health and disease. Of the various systems biology approaches, reconstruction of genome-scale metabolic networks combined with constraint-based modeling has been particularly successful at in silico predicting the phenotypic characteristics of single organisms. Here, we summarize recent studies, which have applied this approach to investigate microbe–microbe and host–microbe metabolic interactions. This approach can be also expanded to investigate the properties of an entire microbial community, as well as single organisms within the community. We illustrate that the constraint-based modeling approach is suitable to model host–microbe interactions at molecular resolution and will enable systematic investigation of metabolic links between the human host and its microbes. Such host–microbe models, combined with experimental data, will ultimately further our understanding of how microbes influence human health.

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► Constraint-based modeling has been applied to the metabolism of single organisms.
► We summarize studies using this approach for microbe–microbe models.
► Host–microbe interactions can also be modeled with this approach.
► We also highlight current challenges in multi-organism modeling.
► This approach is very promising for studying the role of microbes in human health.