Understanding disease-associated metabolic changes in human colon epithelial cells using iColonEpithelium metabolic reconstruction

<p>Background: The human colon epithelium is crucial for metabolic interactions with gut microbiota, which mediates influence of dietary inputs on host metabolism. Colonic epithelial cells have distinct metabolic properties essential for maintaining homeostasis, whose disturbances are associated with inflammatory bowel disease (IBD). However, metabolism of colon epithelium and its interactions with the gut microbiota at the cellular level remains poorly understood.</p>

<p>Method: We analyzed transcriptome data of 188 healthy human colon epithelium samples from the GEO database to build the draft reconstruction of colonic epithelial cells based on the generic human metabolic reconstruction, Recon3D. It was further refined with metabolic reactions and genes specific to colon epithelium and its specificity was tested with metabolic tasks essential to colonic epithelial cells. We used colon carcinoma (Caco-2) cell line for validating findings related to short chain fatty acids and amino acids.</p>

<p>Results: The iColonEpithelium reconstruction consisted of 6551 reactions, 1820 metabolites and 1961 genes. It can achieve essential colonic epithelial cell metabolic functions, like beta-oxidation of butyrate and acetate and tryptophan metabolism. We used it to predict metabolic changes in two case studies: ulcerative colitis (UC) and Crohn’s diseases (CD). </p>

<p>Conclusion and application: We present the first manually curated metabolic reconstruction of human colonic epithelial cells, namely iColonEpithelium, which captures the metabolic signatures of the cell. Ongoing integration of iColonEpithelium with gut microbiome models and multi-omics data will provide deeper insights into the role of colonic epithelial cells in the host-microbiome interactions. It will contribute to predicting dietary effects on host-microbiome metabolism and the metabolic alterations associated with various gut-related disorders.</p>