P021 Microbial metabolite receptors as mediators of pathogenic processes in Inflammatory Bowel Disease.
Spathakis, M.(1,2)*;Dovrolis, N.(1,2);Tarapatzi, G.(1,2);Filidou , E.(1,2);Kandilogiannakis, L.(1,2);Valatas, V.(1,3);Drygiannakis, I.(3);Manolopoulos, V.G.(1,2);Kolios, G.(1,2);Arvanitidis, K.(1,2);Vradelis, S.(4);
(1)Democritus University of Thrace, Laboratory of Pharmacology- Department of Medicine, Alexandroupolis, Greece;(2)Democritus University of Thrace, Individualised Medicine & Pharmacological Research Solutions Center IMPReS, Alexandroupolis, Greece;(3)University of Crete, Gastroenterology and Hepatology Research Laboratory- Department of Medicine, Heraklion, Greece;(4)Democritus University of Thrace, Department of Internal Medicine- Department of Medicine, Alexandroupolis, Greece;
Inflammatory Bowel Disease (IBD) is a chronic inflammatory condition of the alimentary tract, primarily manifested as Crohn’s disease and Ulcerative colitis. Dysbiosis of the intestinal microbial microflora is a well-established characteristic of IBD. The microbiota metabolism ends in the production of several metabolites that participate in interactions with the host and ultimately influence its physiology. Our aim is to investigate whether metabolite receptor expression differs between IBD and healthy individuals and unravel their possible interactions with inflammatory and fibrotic pathways in the intestine.
RNA-sequencing data from over 2500 intestinal biopsy samples were collected from publicly available datasets via the Sequence Read Archive. Bioinformatics analysis of metabolite receptor genes was performed using the RaNA-seq online platform which included normalization, alignment and differential expression. In addition, correlation analysis between the target receptor genes and inflammatory/fibrotic genes as well as functional analysis was performed via a R based pipeline to elucidate molecular interactions during IBD.
The expression of 22 receptors responding to the major metabolite ligand classes bile acids, short chain fatty acids and indole derivatives from tryptophan metabolism was targeted. Several receptors of bile acids as well as receptors of short chain fatty acids, such as the vitamin D receptor (VDR), the peroxisome proliferator-activated receptor alpha (PPARα) and the hydroxycarboxylic acid receptor 2 (HCAR2), were found differentially expressed in intestinal biopsies of CD patients as compared to healthy individuals. Negative and positive correlation of these receptors with genes of known involvement in IBD was explored, along with their simultaneous contributions to inflammatory and fibrotic processes.
Our results demonstrate the interplay between the intestinal microbiota and the host on a metabolite-receptor level and identify disease related interactions with inflammation and fibrosis.
- Posted in: Poster Presentations: Basic Science 2023