ArticleCellular and molecular gastroenterology and hepatology2023
Excess Dietary Sugar Alters Colonocyte Metabolism and Impairs the Proliferative Response to Damage.
Article in Cellular and molecular gastroenterology and hepatology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 22 citations in OpenAlex.
- Gut microbiota and diet in colorectal cancer: Converging determinants of carcinogenesis.Gut microbes · 2026Review
- Dietary Regulation of Intestinal Stem Cell Function: Nutrient-Sensing, Microbiota-Mediated, and Regenerative Mechanisms from a Dietetic Perspective.Biomedicines · 2026Review
- Global landscape of liver disease burden in 1990-2021.iScience · 2026Article
- Cold Exposure Alleviates Colitis via Parallel Integration of Colonic Mucosal Regeneration and Ileal Antimicrobial Defense.Biomedicines · 2026Article
- Metabolic regulation of gut barrier integrity in IBD: protein, lipid, and carbohydrate pathways.Frontiers in nutrition · 2026Review
- Eicosapentaenoic acid enhances intestinal stem cell-mediated colonic epithelial regeneration by activating the LSD1-WNT signaling pathway.Journal of advanced research · 2025Article
- Astragaloside IV Alleviates Fructose-Induced Intestinal Metabolic Senescence by Targeting Ketohexokinase Asn261/Ala226 to Preserve Intestinal Stem Cell Homeostasis.ACS central science · 2025Article
- Roles of intestinal stem cells in inflammatory bowel disease pathogenesis.World journal of stem cells · 2025Review
- Nanoparticle Formulations for Intracellular Delivery in Colorectal Cancer Therapy.AAPS PharmSciTech · 2025Article
- Intraduodenal administration of Reg3g improves gut barrier function and mitigates hepatic steatosis in mice.American journal of physiology. Endocrinology and metabolism · 2025Article
- Health Benefits of Montmorency Tart Cherry Juice Supplementation in Adults with Mild to Moderate Ulcerative Colitis; A Placebo Randomized Controlled Trial.Life (Basel, Switzerland) · 2025Article
- Intestinal stem cell niche: An upcoming area of immense importance in gastrointestinal disorders.Indian journal of gastroenterology : official journal of the Indian Society of Gastroenterology · 2025Review
- Metabolomics reveals soluble epoxide hydrolase as a therapeutic target for high-sucrose diet-mediated gut barrier dysfunction.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Advances in research on the role of high carbohydrate diet in the process of inflammatory bowel disease (IBD).Frontiers in immunology · 2024Review
- Nutrigenomic underpinnings of intestinal stem cells in inflammatory bowel disease and colorectal cancer development.Frontiers in genetics · 2024Review
Corrections and comments
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Authors and funding
20 authors at 5 institutions in 2 countries.
Funding
Abstract
BACKGROUND &
aimsThe 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.
methodsHere, 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.
resultsWe 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.
conclusionsTaken 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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.