Artificial sweeteners: Artificial sweeteners are often marketed as a low-calorie alternative to sugar, but fresh research is adding to questions about what they may be doing inside the body over time.
A new study in mice has found that two widely used non-nutritive sweeteners, sucralose and stevia, may alter the gut microbiome, affect gene activity linked to metabolism and inflammation, and trigger changes that appear to carry into the next generation.
The research, led by scientists at the Universidad de Chile and published in Frontiers in Nutrition, does not claim that sweeteners directly cause obesity, diabetes, or heart disease. But the findings add to a growing body of work examining whether these sugar substitutes may influence metabolic health in more complex ways than previously understood.
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Lead author Dr Francisca Concha Celume said the team was struck by the fact that rising consumption of these additives has not been matched by a drop in obesity or metabolic disorders such as insulin resistance. She said that does not mean sweeteners are to blame, but it does raise important questions about how they may be affecting the body’s internal systems.
For the study, researchers divided 47 male and female mice into three groups. One group was given plain water, while the others received water containing either sucralose or stevia in amounts designed to reflect what a human might consume in a normal diet. Those mice were then bred across two generations, with the later generations given only plain water.
The team then examined how the animals handled glucose, analysed stool samples for changes in gut bacteria, and measured short-chain fatty acids, compounds produced by the microbiome that are considered important for gut and metabolic health. Researchers also studied the activity of genes linked to inflammation, metabolism, and gut barrier function in the liver and intestines.
What they found varied depending on the sweetener and the generation being studied.
In the first generation, impaired glucose tolerance appeared only in male offspring of mice that had consumed sucralose. By the second generation, researchers found elevated fasting blood sugar in male descendants of the sucralose group and female descendants of the stevia group.
Both sweetener groups also showed changes in the gut microbiome and lower levels of short-chain fatty acids, suggesting the animals were producing fewer beneficial microbial by-products. The effects appeared to persist in later generations as well. According to the researchers, sucralose had the stronger and more lasting impact, with more harmful bacteria and fewer beneficial strains seen in the animals’ stool samples.
The gene analysis pointed in a similar direction. Sucralose appeared to increase the activity of genes linked to inflammation while reducing the expression of genes involved in metabolism, and these effects were still visible two generations later. Stevia also affected gene expression, but the impact was milder and did not appear to last as long.
Even so, the researchers cautioned against overinterpreting the results. The mice did not develop diabetes, and the observed changes were described as early biological signals rather than proof of disease. Concha said the findings may point to increased vulnerability to metabolic problems under certain conditions, such as a high-fat diet, but they do not establish a direct cause-and-effect relationship.
The team also stressed that results seen in mice cannot be assumed to apply in exactly the same way to humans. Their aim, the researchers said, is not to create panic, but to encourage further study into the long-term effects of these commonly used additives. In the meantime, they suggested moderation may be a reasonable approach.