The human microbiome is intimately linked to both human health and disease. In recent years, the field has advanced from association based 16S rRNA profiling to high-resolution metagenomic sequencing and experimental validation systems to fulfil fundamental Koch’s postulate. Development of methods to culture the bacteria and the resulting improvements in methods to computationally analyse metagenomic datasets have unlocked both deeper understanding of host-microbe interactions and the ability to experimentally validate these relationships. However, these approaches are regularly focused on faecal samples that may not represent an actual community structure within the human gastrointestinal system and thus fail to model functionally relevant microbe-microbe or host-microbe interactions. Applying novel methods for clinical sampling and advanced culturing techniques we have now cultured over 7000 isolates from over 100 patients and developed methods for targeted analysis of host-microbe interactions in patients with inflammatory bowel disease. Application of these methods to this patient cohort has resulted in identification of key bacterial candidates with a potential role in disease progression and outcomes that may be suitable for targeted clinical interventions.