A new study in mice is raising questions about how artificial sweeteners might affect metabolism over time, including whether those effects could extend to future generations. Researchers found that mice given sucralose or stevia showed changes in gut bacteria and gene activity linked to metabolism and inflammation, with some of those changes observed in their offspring.
The findings, published in Frontiers in Nutrition, are early and limited to animal models. The study does not show that artificial sweeteners cause disease in humans, but it highlights biological pathways scientists are continuing to investigate.
To explore these effects, researchers gave mice water containing either sucralose, stevia or no sweetener, using doses intended to reflect typical human consumption. The mice were then bred, and their offspring were studied over two generations, even though those offspring were not directly exposed to the sweeteners.
“Animal models allow us to control environmental conditions very precisely and to isolate the effect of a specific factor, such as a dietary compound, while also following several generations within a relatively short time,” said lead author Dr. Francisca Concha Celume of the Universidad de Chile.
The researchers found that both sweeteners were associated with changes in the gut microbiome, including lower levels of short-chain fatty acids, compounds produced by gut bacteria that play a role in metabolic health. Some offspring also showed differences in how their bodies processed glucose, an early marker linked to insulin sensitivity.
“The changes we observed in glucose tolerance and gene expression could be interpreted as early biological signals related to metabolic or inflammatory processes,” Concha said. “For example, the animals did not develop diabetes. Instead, what we observed were subtle changes in how the body regulates glucose and in the activity of genes associated with inflammation and metabolic regulation.”
The effects varied by sweetener and by generation. Sucralose was associated with more persistent changes in gut bacteria and gene expression, while stevia’s effects appeared smaller and did not extend as far across generations.
“When we compared generations, these effects were generally strongest in the first generation and tended to decrease in the second generation,” Concha said. “Overall, the effects linked to sucralose were more consistent and persistent across generations.”
Importantly, these findings do not translate directly to human health. Animal studies are useful for identifying potential mechanisms, but human diets, environments and long-term health outcomes are far more complex. The study also looked at early biological markers rather than disease outcomes, making it difficult to draw conclusions about real-world risk.
The results come at a time when artificial sweeteners are widely used as a way to reduce added sugar intake. While some research has raised questions about their effects on metabolism and gut health, findings remain mixed, and major health organizations continue to evaluate the evidence.
“This does not mean that sweeteners are responsible for these trends, but it raises the question of whether they influence metabolism in ways we do not yet fully understand,” Concha said.
For now, the study adds to a growing body of research suggesting that the effects of artificial sweeteners may be more complex than previously thought, but far from settled.
The study was supported in part by Chile’s National Fund for Health Research and Development (FONIS), the National Agency for Research and Development (ANID) and the Digestive Physiology Laboratory at the University of Chile.