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Excess dietary sugar alters colonocyte metabolism and impairs the proliferative response to damage
The colonic epithelium needs constant renewal from crypt-resident intestinal stem cells (ISCs) and transit-amplifying (TA) cells to maintain barrier integrity, particularly after an inflammatory injury. The amount of sugar, such as sucrose, in high-income countries’ diets is rising. Although ISCs and TA cells are sensitive to dietary metabolites, it is still being determined if too much sugar directly impacts how they operate. In this study by Burr et al. (2023), the authors demonstrate the direct impact of sugar on the metabolic, transcriptional, and regenerative capabilities of crypt ISCs and TA cells using a combination of 3-dimensional colonoids and a mouse model of colon damage/repair (dextran sodium sulfate colitis). The authors observed that high-sugar environments directly restrict adenosine triphosphate levels, the expression of proliferative genes, and pyruvate buildup in murine and human colonoids. The development of colonoids was restored after treatment with dichloroacetate, which drives pyruvate into the tricarboxylic acid cycle. Studies on the crypt cells of mice fed a high-sugar diet revealed decreased ISC gene expression, hindered proliferative potential, and enhanced glycolytic potential without corresponding increases in aerobic respiration. In combination, administering dextran sodium sulfate to animals given a high-sugar diet resulted in significant, irreversible damage unrelated to the colonic microbiota or its metabolites. In conclusion, the authors comment that their findings show how short-term, excessive dietary sucrose can directly influence intestinal crypt cell metabolism and prevent the proliferation of ISC/TA cells used for regeneration processes. This information could help diets that support the treatment of acute intestinal damage more effectively. [NPID: Colitis, DCA, mitochondria, renewal, stemness]
Year: 2023
