Inflammatory bowel disease (IBD) is a chronic, incurable condition, comprised of Crohn’s Disease and Ulcerative Colitis. Over 20% of IBD is diagnosed in childhood; however, there are no universally effective treatments and clinical management is complicated by a plethora of side-effects. Until recently, investigation of the microbiota has been limited by an inability to culture the majority of intestinal bacteria. This led to reliance on microbial sequencing to understand bacterial community structure; however, sequencing is limited by an inability to unambiguously identify causative bacteria.
Applying our recently developed culturing techniques (1), we investigated the microbiota in PIBD patients presenting for colonoscopy at Monash Medical Centre. Mucosal biopsy samples were collected across three intestinal regions (terminal Ileum, caecum and rectum) in order to characterise microbial signatures among a PIBD cohort. Microbial analysis was complemented with examination of the inflammatory responses initiated at the sites sampled from. We investigated 12 genes of interest (IL6, IL8, IL12, IL17A, IL17F, IL23, CXCL10, TNF-α, STAT3, TREM1, EPCAM, IFN-γ).
Culturing allowed 1748 bacterial isolates to be picked, which generated 1209 high-quality sequences. We identified 415 known and 325 putative novel species. Enrichment analyses were performed and correlated with the strength of inflammatory responses initiated, which identified four therapeutic candidates. Future functional characterisation and experimental validation of these candidates will be required to assess their potential roles in disease exacerbation and control.