The opportunities for therapeutic interventions targeting the gastrointestinal microbiota are now clear. From chronic infections to inflammatory bowel disease, microbiome-based medicines have demonstrated remarkable efficacy and enormous promise. Despite these opportunities, fundamental microbiological understanding and knowledge of bacterial roles within the gastrointestinal tract remains limited. To address this gap, we have established an extensive human microbiome culture collection (AusMiCC), developed high-resolution metagenomic sequencing, taxonomy agnostic analysis methodologies and genome scale modelling approaches to understand host-microbiome interactions and ecology.
Combining cohort specific bacterial culturing (6,620 isolates) combined with matched metagenomics and host transcriptomic analysis across three intestinal sites (terminal ileum, cecum and rectum; n=386) we identify functionally distinct bacterial clades associated with either inflammatory bowel disease or health. In vitro validation of these newly defined clades demonstrates differential cell cytotoxicity and inflammatory signalling responses consistent with the colonic mucosa responses observed in patients. These data demonstrate the importance of clade specific phenotypes and consideration of host microenvironments when developing and designing therapeutic interventions based on the microbiome.