Comparative effects of different sugar substitutes: Mogroside V, stevioside, sucralose, and erythritol on intestinal health in a type 2 diabetes mellitus mouse.

Intestinal health disorders significantly contribute to the development of type 2 diabetes mellitus (T2DM). Sugar substitutes such as mogroside V (MOG), stevioside (ST), sucralose (TGS), and erythritol (ERT), are increasingly used in T2DM management as alternatives to sucrose (SUC). However, their effects on intestinal health in T2DM have not been fully compared. In the present study, we established a T2DM mouse model using a high-fat diet and streptozotocin injection. These mice were treated with equal doses of SUC, MOG, ST, TGS, or ERT for 4 weeks to evaluate the effects of these sugar substitutes on intestinal health in T2DM. T2DM mice exhibited increased intestinal permeability, reduced goblet cell numbers, elevated pro-inflammatory cytokine levels, and alterations in both gut microbiota and metabolite composition. After 4 weeks of treatment, MOG showed the most significant benefits. MOG activates the PI3K/AKT pathway, enhancing the expression of tight junction proteins, which improves intestinal barrier function and reduces permeability. This is accompanied by NF-κB inhibition, leading to reduced pro-inflammatory cytokine production and increased mucus secretion. These changes help maintain healthy gut microbiota and metabolites, preventing pathogenic bacteria from entering the bloodstream. ST downregulates NF-κB to alleviate intestinal inflammation and improves gut microbiota and metabolic homeostasis in T2DM. ERT has less beneficial effects. TGS and SUC reduce intestinal inflammation and have a better effect on the duodenum. However, TGS has a negative effect on the colon microbiota and metabolites, whereas SUC has a negative effect on the colon microbiota alone. MOG improved intestinal health in T2DM by modulating the PI3K/AKT and NF-κB pathways, whereas ST primarily modulated NF-κB to alleviate intestinal inflammation. Both treatments were effective, with MOG showing the best performance. Therefore, MOG can be considered a viable alternative to SUC for T2DM management.