Consuming sweeteners, like sucralose and stevia, may influence an individual’s health and the health of future generations, reports a new study in mice.
Sweeteners were found to have a negative effect on gene expression and microbiome composition, which was passed down to offspring.
Potential long-term effects of non-nutritive sweeteners
Non-nutritive sweeteners are a sugar alternative that can be over 200 times sweeter than sugar but contain few or no calories. They were originally developed to mitigate the metabolic consequences of excessive sugar intake. Now, they are commonly used in ultra-processed foods and diet sodas, and can help people to manage caloric intake, blood sugar, and weight.
However, concerns are being raised about the adverse effects of non-nutritive sweeteners, with studies indicating they may accelerate cognitive decline, increase heart attack and stroke risk, and suppress immune cells.
Sweeteners may also interfere with energy metabolism and potentially increase the risk of metabolic diseases, including diabetes and cardiovascular disease.
“We found it intriguing that despite the growing consumption of these additives, the prevalence of obesity and metabolic disorders such as insulin resistance has not declined,” said lead author of the paper, Dr. Francisca Concha Celume from the University of Chile. “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.”
How non-nutritive sweeteners affect future generations
Concha Celume and their team set out to understand the long-term effects of sweetener intake on the gut microbiome and metabolic health, and whether it influences future generations.
Mice were split into three groups—one received plain water, and the other two received water with either stevia or sucralose. The dose of sweetener given was comparable to how much a person might consume in a normal diet.
Stevia vs sucralose
Stevia and sucralose are both popular, Food and Drug Administration-approved non-nutritive sweeteners. Stevia is a combination of glycosides derived from the plant Stevia rebaudiana, so it is considered a natural non-nutritive sweetener. Sucralose is an artificial sweetener, a synthetic disaccharide produced from sucrose.
The mice were bred for two generations, which both received plain water. Intestinal and liver expression profiling of Tlr4, Tnf, Tjp1, and Srebp1—genes involved in inflammation, metabolism, and cell–cell adhesion—was performed on each generation. These genes were selected to provide insight into some of the factors that may be behind the negative health impacts of non-nutritive sweeteners.
Fecal samples were taken to analyze changes to the gut microbiome and the concentration of short-chain fatty acids (SCFAs).
Short-chain fatty acids (SCFAs)
SCFAs are produced during gut bacteria metabolism, and they can epigenetically regulate gene expression. These epigenetic changes are transmissible from parent to offspring. Decreased levels of SCFAs impair insulin sensitivity and increase inflammation and oxidative stress, promoting glucose intolerance.
Each generation was also tested for glucose sensitivity.
Different sweetener, different effects
Each sweetener had slightly different effects on each generation.
In the mice fed the sweeteners, there was no change in glucose tolerance for either group. However, the first- and second-generation offspring of sucralose-fed mice had an impaired response to glucose.
The effects of stevia on glucose tolerance were milder than those of sucralose and were only observed in the first-generation offspring.
In the intestines of mice that received sucralose, genes linked to inflammation (Tlr4 and Tnf) were overexpressed. Expression of Srebp1 in the liver, which regulates lipid synthesis, was reduced in these mice. Overexpression of the inflammation-linked genes persisted in the first-generation offspring, and the change to Srebp1 persisted in both the first- and second-generation offspring.
For the mice that consumed stevia, smaller changes to gene expression were observed and were passed onto the first-generation offspring, but not the second.
No changes to the expression of Tjp1 were observed in either sweetener-fed group or the following generations.
These results suggest that consumption of sucralose or stevia induces persistent changes in metabolic and inflammatory gene expression, which are transmitted across generations and may affect offspring health.
Sweeteners influenced microbiomes
Both sweetener-fed groups had more diverse fecal microbiomes than the control, with the mice that received sucralose more severely affected—they had higher numbers of pathogenic gut bacteria and fewer beneficial species.
Both groups also had lower concentrations of SCFAs in fecal samples, suggesting that gut microbiome metabolism was altered and that the bacteria were producing fewer metabolites.
These changes to the microbiomes and SCFAs were also seen in the next generations, with the greatest impact seen in the mice fed the sweeteners and their first-generation offspring.
“The changes we observed in glucose tolerance and gene expression could be interpreted as early biological signals related to metabolic or inflammatory processes,” said Concha Celume. “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. It is possible that such changes could increase susceptibility to metabolic disturbances under certain conditions, such as a high-fat diet.”
Further investigation is needed
While this research identifies a link between non-nutritive sweetener consumption and glucose tolerance, microbiota composition, and gene expression, it doesn’t establish a causative mechanism.
Future research may focus on clarifying the mechanisms behind the intergenerational effects of non-nutritive sweeteners and identifying whether they are reversible.
As the work was performed in mice, additional research is needed to confirm whether non-nutritive sweeteners have similar effects in humans.
“The goal of this research is not to create alarm, but to highlight the need for further investigation,” said Concha Celume. “It may be reasonable to consider moderation in the consumption of these additives and to continue studying their long-term biological effects.”
Reference: Concha Celume F, Perez-Bravo F, Magne F, Olivares R, Gotteland M. Artificial and natural non-nutritive sweeteners drive divergent gut and genetic responses across generations. Front Nutr. 2026. doi: 10.3389/fnut.2026.1694149
This article is a rework of a press release issued by Frontiers. Material has been edited for length and content.
