Understanding disease-associated metabolic changes in human colonic epithelial cells using the iColonEpithelium metabolic reconstruction
Boyu Jiang, Nick Quinn-Bohmann, Christian Diener, Vignesh Bose Nathan, Yu Han-Hallett, Lavanya Reddivari, Sean M. Gibbons, Priyanka Baloni
Abstract
The colonic epithelium plays a key role in the host-microbiome interactions, allowing uptake of various nutrients and driving important metabolic processes. To unravel detailed metabolic activities in the human colonic epithelium, our present study focuses on the generation of the first cell-type-specific genome-scale metabolic model (GEM) of human colonic epithelial cells, named iColonEpithelium. GEMs are powerful tools for exploring reactions and metabolites at the systems level and predicting the flux distributions at steady state.
Introduction
The human colon plays an important role in the host metabolism, coordinating dietary nutrient absorption and interactions with the colonic microbiota [1]. The colonic epithelium serves as a barrier and helps to regulate mucosal and systemic immunity, physiology, and metabolism, mediated in part by interactions with the gut microbiota [2].
Materials and method
Collection of transcriptome data and cross-platform normalization
We searched NCBI’s GEO database (https://www.ncbi.nlm.nih.gov/geo/) and collected transcriptome data of human colonic epithelial cell from published studies with the following criteria: (1) clear description of sample sources, which were from human colon epithelium; (2) inclusion of samples from healthy volunteers; (3) availability of raw data; (4) data published within the last 10 years.
Results
Metabolic reconstruction of human colonic epithelial cells: iColonEpithelium
We generated the first human colonic epithelial cell-type-specific metabolic network using the generic human reconstruction, Recon3D [19], as the template (see Methods). iColonEpithelium metabolic reconstruction has 6651 reactions, 4072 metabolites, and 1954 genes (Tables A, B, and C in S1 Data). We used transcriptome data of colonic epithelial cells from healthy individuals to build the reconstruction (Table D in S1 Data).
Discussion
In this study, we present a metabolic reconstruction of human colonic epithelial cells, iColonEpithelium, which is useful for predicting metabolic phenotypes in the gut epithelium at the cellular level.
Acknowledgments
We thank the EMBRIO Institute, Purdue University, for providing laboratory space for Baloni lab members that facilitated this work.
Citation: Jiang B, Quinn-Bohmann N, Diener C, Nathan VB, Han-Hallett Y, Reddivari L, et al. (2025) Understanding disease-associated metabolic changes in human colonic epithelial cells using the iColonEpithelium metabolic reconstruction. PLoS Comput Biol 21(7): e1013253. https://doi.org/10.1371/journal.pcbi.1013253
Editor: Kiran R. Patil, University of Cambridge, UNITED KINGDOM OF GREAT BRITAIN AND NORTHERN IRELAND
Received: November 5, 2024; Accepted: June 17, 2025; Published: July 3, 2025
Copyright: © 2025 Jiang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: The code developed for this study is available at https://doi.org/10.4231/DNBT-5G17 and https://github.com/BaloniLab/iColonEpithelium.
Funding: Research reported in this publication was supported by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health under award number R01DK133468 (to S.M.G.) The funders did not play any role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: We have read the journal’s policy and the author of this manuscript have the following competing interests: S.M.G. is a paid member of the Thorne Scientific Advisory Board. This role is entirely unrelated to the research reported in this manuscript.
