Background: Enterochromaffin (EC) cells line the GI tract and produce almost all serotonin (5-HT) - a critical regulator of GI function and metabolism - in the body1. EC cells are sensors, and nutrients like dietary sugars can trigger 5-HT release from EC cells, potentially impacting metabolic disorders and gut function2. The increasing consumption of dietary sugars, like fructose and lactose, are associated with poor diet quality, obesity, and Type 2 Diabetes (T2D). Many people, particularly those with T2D, also rely on artificial sweeteners, like Equal®, as sugar alternatives3. However, the mechanisms by which consuming sugars and artificial sweeteners may drive GI disturbance and poor metabolic outcomes remain unclear. We aimed to assess whether dietary sugars and artificial sweeteners impact the GI mucosa directly, focussing on EC cell density and using small intestine organoids.
Methods: Mouse small intestinal organoids were exposed to dietary levels of fructose, lactose, and Equal® (aspartame and acesulfame K) continuously for 5 days. Organoids were then stained for 5-HT, Epcam and Ki67 to assess the effect of stimuli on: EC cell density, organoid size, and proliferation, respectively. Data were collected using fluorescent confocal microscopy and analysed with Image J.
Results: Fructose and lactose significantly decreased organoid size and proliferation but had no effect of EC cell density. Equal® did not have a significant effect on organoid size or proliferation, but significantly increased EC cell density.
Conclusions: Our results reveal that chronic exposure to dietary sugars and artificial sweeteners differentially affect the small intestinal GI mucosa, with Equal® having the greatest impact on EC cell density. This occurs independent of any changes in the gut microbiome and metabolite production. These data highlight a mechanism by which the consumption of foods rich in sugars and artificial sweeteners may contribute to health burdens like obesity, diabetes, and GI dysfunction.