A study published in Frontiers in Nutrition by researchers from the Universidad de Chile investigated the potential long-term metabolic effects of two widely used non-nutritive sweeteners—sucralose and stevia—using a multi-generational mouse model. The researchers divided 47 male and female mice into three groups, with one group receiving plain water and the other two groups receiving water containing sucralose or stevia at doses comparable to human consumption. The mice were then bred for two successive generations, with only the original generation exposed to the sweeteners; subsequent generations received plain water. The study assessed oral glucose tolerance, fecal microbiome composition, short-chain fatty acid concentrations, and the activity of five genes involved in inflammation, gut barrier integrity, and metabolism across all generations.
The findings revealed distinct and, in some cases, intergenerational effects of the sweeteners on metabolic health markers. First-generation male offspring of mice consuming sucralose exhibited impaired glucose tolerance, while second-generation male descendants of the sucralose group and female descendants of the stevia group showed elevated fasting blood sugar levels. Both sweeteners led to more diverse fecal microbiomes but with reduced short-chain fatty acid production, a pattern persisting into subsequent generations. Sucralose exposure resulted in more pronounced and longer-lasting changes, including alterations in gut microbiome composition favoring potentially pathogenic bacteria, increased inflammatory gene activity, and decreased metabolic gene activity, effects detectable two generations after initial exposure. Stevia also altered gene expression, but these changes were weaker and did not extend beyond the first generation. The researchers emphasize that while the study demonstrates associations between sweetener exposure and metabolic changes, it does not establish causation and note that results from mouse models may not directly translate to humans, advocating for further investigation into the long-term biological impacts of non-nutritive sweeteners. Source