The pathogenesis of IBD, involving dynamic interactions between the microbiome, innate and adaptive immune systems, genetics and environmental factors, is a major focus of academic interest, in order to reveal more about the heterogeneous clinical course of the disease and in pursuit of improved therapeutic targets.
Metabonomics has been previously used with a variety of biofluids to successfully distinguish IBD from controls, but the complex metabolic data also have potential to unlock insights into pathogenesis and better understand how to better stratify patients for personalised clinical care.
In the largest urinary metabonomics IBD study to date, changes in the white European cohort confirmed previous published findings, highlighting discriminatory metabolites of gut microbial and inflammatory pathway sources. Significant metabolic differences were seen when comparing IBD patients and controls from South Asia to white North Europeans, demonstrating the influence of ethnicity on the metabolic profile and showing metabolite changes related to host-nutrition-microbiome interactions.
Results from longitudinal measurements of the IBD metabolome in the same individuals over several years indicate relative stability despite the relapsing-remitting course of the disease and different treatments. This early finding suggests clinical outcomes may only have subtly discernible changes on metabolic profiles, potentially limiting its application as a disease-monitoring tool.
16S rRNA profiling, employed to characterise the microbiome, showed reduced microbial diversity in IBD and 4 key bacterial genera - Veillonella, Acidaminococcus, Lactobacillus and Streptococcus - associated with disease. Significant urinary and faecal metabolites in the same patients were correlated with these bacteria to demonstrate the feasibility of multi-omic integration in IBD.
Furthermore, the breath VOC profiles of IBD patients obtained by SIFT-MS were distinct from those of heathy controls, with the significant compounds originating from microbial sources, and inflammatory pathways, demonstrating the potential of this technology and another facet to metabolic profiling in IBD.