Therapies aiming to restore people’s health via the human gut microbiome have great potential, but many therapies trialled to date have achieved only transient effects or failed completely. I will talk about challenges and recent advances in characterising microbiomes from a functional and ecological perspective. Using metagenome-wide metabolic modelling and an ecology-guided analytical framework, we are starting to unravel the microbial functions and metabolic interactions that may be leveraged to restore gut health.