Understanding disease-associated metabolic changes in human colonic epithelial cells using the iColonEpithelium metabolic reconstruction.
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-sp...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2025-07-01
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| Series: | PLoS Computational Biology |
| Online Access: | https://doi.org/10.1371/journal.pcbi.1013253 |
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| author | Boyu Jiang Nick Quinn-Bohmann Christian Diener Vignesh Bose Nathan Yu Han-Hallett Lavanya Reddivari Sean M Gibbons Priyanka Baloni |
| author_facet | Boyu Jiang Nick Quinn-Bohmann Christian Diener Vignesh Bose Nathan Yu Han-Hallett Lavanya Reddivari Sean M Gibbons Priyanka Baloni |
| author_sort | Boyu Jiang |
| collection | DOAJ |
| description | 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. Our cell-type-specific iColonEpithelium metabolic reconstruction captures genes specifically expressed in the human colonic epithelial cells. iColonEpithelium is also capable of performing metabolic tasks specific to the colonic epithelium. A unique transport reaction compartment has been included to allow for the simulation of metabolic interactions with the gut microbiome. We used iColonEpithelium to identify metabolic signatures associated with inflammatory bowel disease. We used single-cell RNA sequencing data from Crohn's Diseases (CD) and ulcerative colitis (UC) samples to build disease-specific iColonEpithelium metabolic networks in order to predict metabolic signatures of colonocytes in both healthy and disease states. We identified reactions in nucleotide interconversion, fatty acid synthesis and tryptophan metabolism were differentially regulated in CD and UC conditions, relative to healthy control, which were in accordance with experimental results. The iColonEpithelium metabolic network can be used to identify mechanisms at the cellular level, and we show an initial proof-of-concept for how our tool can be leveraged to explore the metabolic interactions between host and gut microbiota. |
| format | Article |
| id | doaj-art-4e7b68abc3dc4f178330d3725c096d7e |
| institution | Kabale University |
| issn | 1553-734X 1553-7358 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Computational Biology |
| spelling | doaj-art-4e7b68abc3dc4f178330d3725c096d7e2025-08-20T03:30:27ZengPublic Library of Science (PLoS)PLoS Computational Biology1553-734X1553-73582025-07-01217e101325310.1371/journal.pcbi.1013253Understanding disease-associated metabolic changes in human colonic epithelial cells using the iColonEpithelium metabolic reconstruction.Boyu JiangNick Quinn-BohmannChristian DienerVignesh Bose NathanYu Han-HallettLavanya ReddivariSean M GibbonsPriyanka BaloniThe 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. Our cell-type-specific iColonEpithelium metabolic reconstruction captures genes specifically expressed in the human colonic epithelial cells. iColonEpithelium is also capable of performing metabolic tasks specific to the colonic epithelium. A unique transport reaction compartment has been included to allow for the simulation of metabolic interactions with the gut microbiome. We used iColonEpithelium to identify metabolic signatures associated with inflammatory bowel disease. We used single-cell RNA sequencing data from Crohn's Diseases (CD) and ulcerative colitis (UC) samples to build disease-specific iColonEpithelium metabolic networks in order to predict metabolic signatures of colonocytes in both healthy and disease states. We identified reactions in nucleotide interconversion, fatty acid synthesis and tryptophan metabolism were differentially regulated in CD and UC conditions, relative to healthy control, which were in accordance with experimental results. The iColonEpithelium metabolic network can be used to identify mechanisms at the cellular level, and we show an initial proof-of-concept for how our tool can be leveraged to explore the metabolic interactions between host and gut microbiota.https://doi.org/10.1371/journal.pcbi.1013253 |
| spellingShingle | Boyu Jiang Nick Quinn-Bohmann Christian Diener Vignesh Bose Nathan Yu Han-Hallett Lavanya Reddivari Sean M Gibbons Priyanka Baloni Understanding disease-associated metabolic changes in human colonic epithelial cells using the iColonEpithelium metabolic reconstruction. PLoS Computational Biology |
| title | Understanding disease-associated metabolic changes in human colonic epithelial cells using the iColonEpithelium metabolic reconstruction. |
| title_full | Understanding disease-associated metabolic changes in human colonic epithelial cells using the iColonEpithelium metabolic reconstruction. |
| title_fullStr | Understanding disease-associated metabolic changes in human colonic epithelial cells using the iColonEpithelium metabolic reconstruction. |
| title_full_unstemmed | Understanding disease-associated metabolic changes in human colonic epithelial cells using the iColonEpithelium metabolic reconstruction. |
| title_short | Understanding disease-associated metabolic changes in human colonic epithelial cells using the iColonEpithelium metabolic reconstruction. |
| title_sort | understanding disease associated metabolic changes in human colonic epithelial cells using the icolonepithelium metabolic reconstruction |
| url | https://doi.org/10.1371/journal.pcbi.1013253 |
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