A mouse study published in Frontiers in Nutrition suggests that the sucralose and stevia gut microbiome relationship is more complicated than the ‘zero-calorie, therefore harmless’ assumption implies: both sweeteners altered gut bacteria, reduced beneficial metabolites, and changed the activity of genes tied to metabolism and inflammation, with some of those changes appearing in offspring that never consumed the sweeteners at all.
The study was conducted by researchers at the Universidad de Chile, with Dr. Francisca Concha Celume as lead author. It was published on 31 January 2026. The findings do not prove that either sweetener directly caused metabolic disease in the mice, and the researchers are careful to say so. What the data show are associations, not a clean causal chain.
What the Researchers Actually Tested
Forty-seven male and female mice were split into three groups: plain water, water with sucralose, or water with stevia. The doses were calibrated to reflect amounts a person might plausibly consume through normal diet. The animals were then bred across two successive generations, with both later generations receiving only plain water, not the sweeteners. That design was deliberate: it allowed the team to look for effects that persisted beyond direct exposure.
Sucralose is around 600 times sweeter than sugar, according to Inside Precision Medicine, which also notes that stevia is a no-calorie natural alternative extracted from the leaves of a South American plant. Both are widely used precisely because they deliver sweetness without the caloric load of sugar, but their biological interactions downstream of the taste buds are less well understood.
Each generation was assessed for oral glucose tolerance, a standard measure for identifying signs of insulin resistance. The team also examined fecal samples for microbiome composition and levels of short-chain fatty acids, compounds produced by gut bacteria that can influence gene regulation. Separately, the activity of five genes in the liver and intestines was measured, covering inflammation, gut barrier integrity, and metabolism.
Sucralose and Stevia Gut Microbiome Effects Diverged by Generation and Sex
The two sweeteners did not produce identical results, and the pattern shifted between generations. In first-generation offspring, impaired glucose tolerance appeared only in males descended from the sucralose group. By the second generation, elevated fasting blood sugar was found in male descendants of the sucralose group and female descendants of the stevia group. The reasons for those sex-specific differences are not explained by the data.
Both sweeteners increased the diversity of fecal microbiomes in the original animals. That sounds positive until you consider the accompanying finding: short-chain fatty acid levels were lower, suggesting that a more diverse community of gut bacteria was nonetheless producing fewer beneficial metabolites. Reduced short-chain fatty acid concentrations were also detected in both subsequent generations, none of which had consumed either sweetener.
The effects tied to sucralose were, by the researchers’ own account, stronger and more persistent. Mice in the sucralose group showed larger shifts in fecal microbiome composition, with greater numbers of potentially pathogenic bacteria and fewer beneficial species. Sucralose also appeared to increase the activity of genes linked to inflammation while reducing those associated with metabolism, and those gene-expression changes were still detectable two generations after the original exposure. Stevia altered gene expression too, but the changes were weaker and did not persist beyond one generation.
‘When we compared generations, these effects were generally strongest in the first generation and tended to decrease in the second generation,’ Concha Celume said. ‘Overall, the effects linked to sucralose were more consistent and persistent across generations.’
The proposed mechanism runs through short-chain fatty acids. The researchers suggest that both sweeteners may disrupt normal gut microbiome function, reducing short-chain fatty acid production, which could in turn influence epigenetic processes, meaning changes in gene expression that may be transmitted from parents to offspring without altering the underlying DNA sequence. It is a plausible pathway, but it remains a working hypothesis rather than a demonstrated chain of causation.
The Limits of a Mouse Study
The researchers themselves flag the key caveats. The findings show associations, not proof of direct causation. Mice are not humans, and biological responses to non-nutritive sweeteners may differ between species. The animals did not develop diabetes; what the team observed were, as Concha Celume put it, ‘subtle changes in how the body regulates glucose and in the activity of genes associated with inflammation and metabolic regulation.’
‘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,’ Concha Celume said, before adding the necessary qualification: ‘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.’
The team’s stated aim is not to recommend that consumers discard every diet drink, but to argue that long-term biological effects of non-nutritive sweeteners require further investigation, including studies that track intergenerational outcomes in humans. The paper itself, published in Frontiers in Nutrition under DOI 10.3389/fnut.2026.1694149, is the clearest next step to read if you want to assess the methodology directly.
