It has been long recognised that the gut microbiome not only varies throughout the length of the gastrointestinal tract but also between the lumen and mucosal surfaces of different gut segments. However, the sampling, quantification, and characterisation of these mucosa-associated communities has been constrained by the nature of the specimens and the utility of omics-based approaches in adequately capturing the microbiology inherent to these communities. This presentation will provide an overview of the approaches developed in Brisbane and used to bring microbial genomes to life, enabled by their application in the clinical setting, and providing new options that can advance translating the microbiome into medicine. Our work in relation to Crohn’s disease pathophysiology, dietary impacts and predictive ecology, and strategies to better diagnose and predict disease course will be highlighted.