Document Type
Article
Publication Date
2023
Publisher
Elsevier
Source Publication
Cellular and Molecular Gastroenterology and Hepatology (CMGH)
Source ISSN
2352-345X
Original Item ID
DOI: 10.1016/j.jcmgh.2023.05.001
Abstract
Background & Aims
The colonic epithelium requires continuous renewal by crypt resident intestinal stem cells (ISCs) and transit-amplifying (TA) cells to maintain barrier integrity, especially after inflammatory damage. The diet of high-income countries contains increasing amounts of sugar, such as sucrose. ISCs and TA cells are sensitive to dietary metabolites, but whether excess sugar affects their function directly is unknown.
Methods
Here, we used a combination of 3-dimensional colonoids and a mouse model of colon damage/repair (dextran sodium sulfate colitis) to show the direct effect of sugar on the transcriptional, metabolic, and regenerative functions of crypt ISCs and TA cells.
Results
We show that high-sugar conditions directly limit murine and human colonoid development, which is associated with a reduction in the expression of proliferative genes, adenosine triphosphate levels, and the accumulation of pyruvate. Treatment of colonoids with dichloroacetate, which forces pyruvate into the tricarboxylic acid cycle, restored their growth. In concert, dextran sodium sulfate treatment of mice fed a high-sugar diet led to massive irreparable damage that was independent of the colonic microbiota and its metabolites. Analyses on crypt cells from high-sucrose–fed mice showed a reduction in the expression of ISC genes, impeded proliferative potential, and increased glycolytic potential without a commensurate increase in aerobic respiration.
Conclusions
Taken together, our results indicate that short-term, excess dietary sucrose can directly modulate intestinal crypt cell metabolism and inhibit ISC/TA cell regenerative proliferation. This knowledge may inform diets that better support the treatment of acute intestinal injury.
Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 4.0 International License.
Recommended Citation
Burr, Ansen H.P.; Ji, Junyi; Ozler, Kadir; Mentrup, Heather L.; Eskiocak, Onur; Yueh, Brian; Cumberland, Rachel; Menk, Ashley V.; Rittenhouse, Natalie; Marshall, Christopher; Chiaranunt, Pailin; Zhang, Xiaoyi; Mullinax, Lauren; Overacre-Delgoffe, Abigail; Cooper, Vaughn S.; Poholek, Amanda C.; Delgoffe, Greg M.; Mollen, Kevin P.; Beyaz, Semir; and Hand, Timothy W., "Excess Dietary Sugar Alters Colonocyte Metabolism and Impairs the Proliferative Response to Damage" (2023). Biological Sciences Faculty Research and Publications. 958.
https://epublications.marquette.edu/bio_fac/958
Comments
Accepted version. Cellular and Molecular Gastroenterology and Hepatology (CMGH), Vol. 16, No. 2 (2023): 287-316. DOI. © 2023 Elsevier. Used with permission.