Choosing a diet soda or sugar-free version of a favorite drink often means consuming nonnutritive sweeteners, which provide sweetness without the calories or nutrients found in sugar. Although these additives can help reduce calorie intake, researchers continue to investigate their possible long-term effects on energy metabolism, blood sugar regulation, diabetes risk, and cardiovascular health.
A new study in mice adds to the growing discussion. Researchers found that sucralose and stevia—two widely used low- and no-calorie sweeteners—may alter the gut microbiome and influence gene activity linked to metabolic health. Some of these changes were also detected in later generations, even after the offspring stopped consuming the sweeteners.
“We found it interesting that despite the increased consumption of these additives, the prevalence of metabolic disorders such as obesity and insulin resistance has not decreased,” said Dr. Francisca Concha Serme of the University of Chile, lead author of the study published in Frontiers in Nutrition. “This does not mean that sweeteners are responsible for these trends, but it does raise the question of whether sweeteners influence metabolism in ways that we do not yet fully understand.”
Testing sucralose and stevia across generations
The researchers divided 47 male and female mice into three groups. One group received plain water, while the other two groups received water containing either sucralose or stevia. The doses were designed to reflect amounts a person might reasonably consume as part of a typical diet.
The mice were then bred for two consecutive generations. Unlike the original animals, both subsequent generations received only plain water, allowing researchers to examine whether any biological effects continued after exposure ended.
“Animal models allow us to control environmental conditions very precisely and isolate the effects of specific factors, such as dietary compounds, while also allowing us to follow several generations over a relatively short period of time,” Concha explained.
Tracking blood sugar, gut bacteria, and gene activity
Researchers tested each generation using an oral glucose tolerance test. This test measures how effectively the body processes glucose and can reveal signs of impaired blood sugar regulation or insulin resistance, an important risk factor for type 2 diabetes.
The team also collected fecal samples to analyze the gut microbiome and measure levels of short-chain fatty acids. Produced by gut bacteria, these compounds influence several biological processes, including inflammation, metabolism, and gene regulation.
Changes in short-chain fatty acid levels may also point to epigenetic effects—biological changes that influence gene activity without altering the DNA sequence and that may potentially be passed from parent to offspring.
Scientists suspect that nonnutritive sweeteners may change short-chain fatty acid production by disrupting the normal balance of gut bacteria. These changes could then affect gene expression and metabolic function.
The researchers also measured the activity of five genes in the liver and intestines. These genes are involved in inflammation, intestinal barrier function, and metabolism. Examining their activity helped the team investigate whether sweetener exposure was associated with biological changes related to gut health, inflammation, and metabolic regulation.
Sucralose and stevia produce different effects
The two sweeteners did not affect the mice in exactly the same way, and the observed effects varied between generations.
Among first-generation offspring, signs of glucose intolerance appeared only in males whose parents had consumed sucralose. By the second generation, fasting blood sugar levels were higher in male offspring from the sucralose group and female offspring from the stevia group.
Mice that consumed either sweetener developed a more diverse fecal microbiome but had lower concentrations of short-chain fatty acids. This combination may indicate that the gut bacteria were producing fewer beneficial metabolites. Reduced short-chain fatty acid levels were also detected in both subsequent generations.
The effects linked to sucralose appeared stronger and longer-lasting. Mice exposed to sucralose experienced significant changes in their fecal microbiome, including an increase in potentially harmful bacteria and a decrease in beneficial bacterial species.
Sucralose-related changes lasted longer
Sucralose also appeared to increase the activity of genes associated with inflammation while reducing the activity of genes involved in metabolism. These changes remained detectable two generations after the original exposure.
Stevia also affected gene expression, but the changes were weaker and did not continue beyond one generation.
“When comparing generations, these effects were generally strongest in the first generation and tended to decline in the second generation,” Concha said. “Overall, the effects associated with sucralose were more consistent and durable across generations.”
“The observed changes 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 the way the body regulates glucose and in the activity of genes associated with inflammation and metabolic regulation. Such changes could increase susceptibility to metabolic disorders under certain conditions, such as a high-fat diet.”
What mouse research can—and cannot—tell us
The researchers emphasized that the findings show an association between exposure to sucralose or stevia and changes in gut bacteria, gene activity, and metabolic health. However, the study does not prove that the sweeteners directly caused every effect observed.
Because the research was conducted in mice, the results may not apply directly to humans. Differences in biology, diet, gut microbiomes, and sweetener consumption patterns could produce different responses in people.
“The purpose of this study is not to stir up fear, but to highlight the need for further research,” Concha said. “It may be reasonable to consider moderation when consuming these additives while scientists continue to study their long-term effects on the gut microbiome, blood sugar regulation, and metabolic health.”
Source: www.sciencedaily.com