Artificial sweeteners added to "zero-calorie" beverages in place of sugar may affect gut microbiota and gene expression, with these effects potentially passed down to grandchildren, according to an animal study.
A team led by Dr. Francisca Concha Celume at the University of Chile recently reported in the international journal Frontiers in Nutrition that the artificial sweeteners sucralose and stevia caused metabolic and inflammation-related changes in mice, with some effects carrying over to subsequent generations.
Sucralose is a synthetic sweetener that is 600 times sweeter than sugar but is not metabolized for energy in the body, making it considered "zero-calorie." Stevia is also far sweeter than sugar but contains almost no calories because it is not digested or metabolized in the body.
The researchers divided 47 male and female mice into three groups and fed them for 16 weeks with either plain water, water mixed with sucralose (0.1 mg/mL), or water mixed with stevia (0.1 mg/mL). They then mated these mice (the F0 generation) to produce the first generation (F1), and mated F1 mice again to produce the second generation (F2). The F1 and F2 generations were not given any sweeteners.
The team analyzed insulin resistance, blood glucose regulation, gut microbiota composition, and short-chain fatty acid concentrations in each generation. They also measured changes in the expression of genes related to inflammation and metabolism (Tlr4, Tnf, Tjp1, Srebp1, etc.) in liver and gut tissues.
The results showed no significant changes in glucose metabolism in the F0 generation, but small changes in blood glucose response appeared in male mice in the sucralose-consuming groups of the F1 and F2 generations. In the F1 generation, changes in glucose tolerance were observed in males of the sucralose group, while in the F2 generation, elevated fasting blood glucose was confirmed in males of the sucralose group and females of the stevia group.
As for gut microbiota, microbial diversity increased in the sweetener-consuming groups, but concentrations of short-chain fatty acids, which are beneficial metabolites, decreased. This reduction in short-chain fatty acids was maintained in the F1 and F2 generations as well.
In particular, the sucralose-consuming group showed an increase in bacterial species with pathogenic tendencies and a decrease in beneficial bacteria, indicating a greater impact on gut microbiota composition.
In terms of gene expression, the sucralose group showed increased expression of inflammation-related genes (Tlr4, Tnf) in the gut, while the expression of a metabolism-related gene (Srebp1) in the liver decreased. These changes continued in the F1 and F2 generations, suggesting that sweeteners consumed by parents could affect the metabolic health of their grandchildren.
The researchers proposed that these changes may be transmitted through epigenetic mechanisms. Sweeteners alter the function of gut microbiota, which reduces the production of short-chain fatty acids, potentially affecting the regulation of gene expression.
However, they added that the results only show an association between sweeteners and changes in health status and do not prove a direct causal relationship, noting that findings from mouse experiments may not directly apply to humans.
"The purpose of this study is not to raise alarm about the dangers of artificial sweeteners, but to raise the need for further research," the team said. "There is a need to consider moderating consumption of artificial sweeteners and to continue studying their long-term biological effects."
The researchers also advised, "These findings support the recommendations of the World Health Organization (WHO)," adding that "the long-term effects on offspring generations should be carefully considered, especially during sensitive periods such as pregnancy and lactation." The WHO has previously stated that it does not recommend the long-term use of non-sugar sweeteners for weight control.
