P077 Metabonomic profiling distinguishes Crohn’s perianal fistulas and idiopathic idiopathic (cryptoglandular) perianal fistulas: possible clues to underlying pathogenesis?
S. Adegbola1, M. Sarafian2, K. Sahnan1, P. Tozer1, N. Ding3, O. Faiz1, J. Warusavitarne1, R. Phillips1, E. Holmes2, A. Hart3
1St. Mark’s Hospital, Department of Colorectal Surgery, Harrow, UK, 2Imperial College London, Computational Systems Division, London, UK, 3St. Mark’s Hospital, Inflammatory Bowel Diseases Unit, Harrow, UK
Background
The reasons why fistulas originate have been explained in idiopathic cases, with the cryptoglandular theory being widely accepted; however, in Crohn ́s disease, it is thought to involve interplay between microbiological, immunological and genetic factors. It remains unclear why fistulas persist. Novel investigative tools in systems biology are improving our understanding of pathogenesis, and one such tool is metabonomic profiling, whereby spectrometry is used to assess metabolic responses of complex systems in health and disease. These changes are mapped using analytical and statistical techniques. To the best our knowledge, these methodologies have not been applied to aid understanding of the pathogenesis of Crohn’s perianal fistula persistence.
Methods
Fistula tissue biopsy was obtained from the fistula tract of 30 patients with idiopathic perianal fistula and 20 patients with Crohn ́s anal fistula. Two analytical platforms were attempted to achieve broad metabolome coverage. Univariate (student t-test) and multivariate statistical data analyses were performed. From the latter principle component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA), models were built to find metabolites that could predict tissue samples from patients with either Crohn’s or idiopathic anal fistula. Metabolite putative identification was conducted by matching accurate mass:charge ratio (
Results
Significant OPLS-DA predictive models (validated with CV-ANOVA
Conclusion
Forty-one differentiating metabolites were discovered belonging to various classes of lipids, amino acids and nucleotides. Pathways involved included amino acid metabolism, phospholipid metabolism and glycerolipid metabolism amongst others. Further work in larger numbers is required to validate these findings as well as cross correlation with microbiome work to understand the impact of host gut interactions in the pathophysiology of Crohn’s and idiopathic perianal fistulas.
- Posted in: Poster presentations: Basic Science 2020