A new study from the University of Chile suggests that common artificial sweeteners may trigger biological changes that are passed down to future generations.
The research focused on sucralose and stevia, two of the world’s most widely used non-nutritive sweeteners (NNS).
The additives could alter gut microbiota, gene expression and metabolism in mice, with some effects persisting in their first- and second-generation offspring, even in offspring who were never directly exposed to the sweeteners, according to the team behind the study.
Francisca Concha, the lead researcher and an assistant professor at the University of Chile, said in an interview that the research was inspired by higher rates of diabetes, obesity and insulin resistance, despite many products containing NNS to replace nutritive sugars.
“This situation raised the question of whether [artificial sweeteners] were truly harmless,” added Concha, who is also a member of the university’s nutrition department.
The team’s paper looked at how artificial and natural NNS drive divergent gut and genetic responses across generations. It was published in the peer-reviewed scientific journal Frontiers in Nutrition in April.
The researchers experimented on groups of mice, giving them the acceptable daily intake approved by the United States Food and Drug Administration for each additive.
They sought to understand the effects on the offspring of the laboratory mice, analysing the effects on the first and second generations that had not been exposed to the additives.
“We found changes in gut microbiota of the consumers ... and their offspring,” the researchers said of the mice.
According to the team, although the research yielded important evidence, it needed to be interpreted with caution because it was based on a laboratory-mouse model and could not be directly extrapolated to humans.
The researchers also stressed that NNS were still considered safe based on current food safety standards.
As for the results, while the mice consuming NNS showed no change in their own glucose tolerance, their sucralose-consuming descendants exhibited a mildly altered metabolic response to sugar.
The altered glucose metabolism, although mild, could increase the risk of metabolic disease, the authors said. This alteration could further represent early signs of insulin resistance, even though the changes found were small.
The research also found that both sucralose and stevia consumption significantly reduced the production of short-chain fatty acids, or by-products of fibre breakdown. Notably, these reduced concentrations persisted and were passed down to subsequent generations.
“It is possible that these effects are enhanced or accumulated in offspring if they also consume NNS,” Concha said. “We believe this is essential to address in future studies.”
Changes in faecal microbiota were found as well, particularly in mice that ingested sucralose and in their first-generation offspring. This faecal microbiota was higher than before.
According to Concha, gut microbiota “has a role in digestion, producing beneficial vitamins and metabolites, regulating the immune system and acting as a barrier against pathogens”.
Fabien Magne, another researcher in the study and also with the University of Chile, said the changes, “with the modification of short-chain fatty acids, suggest that parental exposure to sweeteners, especially sucralose, may harm gut health and increase the risk of metabolic problems in later generations”.
The researchers identified major genetic shifts in mice linked to the consumption of NNS. They found that sucralose and stevia altered the expression of genes governing immune function – Tlr4 and Tnf, respectively – and Srebp-1, a protein that controls fat metabolism.
The Tlr4 were overexpressed in the intestines of mice that ingested sucralose and in their first-generation offspring. In the case of stevia ingestion, a higher expression was found before returning to normal in the second generation.
As for Srebp-1 expression, it was downregulated in the group administered sucralose, a biological trend that persisted across both the first and second generations.
According to Martin Gotteland, a University of Chile lecturer, researcher at its Institute of Nutrition and Technology of Foods and co-author of the paper: “This phenomenon can occur through epigenetic mechanisms, modifying the activity of the genes without altering the DNA sequence.”
When pro-inflammatory genes become more active, they trigger changes that compromise the integrity of the intestinal lining, making it more permeable.
“The consequence is the incorporation of bacteria and toxic molecules into the bloodstream, leading to low-grade systemic inflammation,” Concha said.
The study also found that genes controlling the liver’s handling of glucose and lipids had changed.
“It could be read as a reduced ability to regulate glycaemia, a greater tendency to accumulate liver fat and eventually leading to the development of a non-alcoholic fatty liver and dyslipidaemia,” Concha added.
The researchers noted that just a few genes were analysed, so only a partial picture of the consequences was revealed. They said further studies needed to be conducted to gain a better understanding.
Meanwhile, the debate about sugar versus NNS in sweetened diets is still being widely studied, with the challenges of balancing a healthy diet, reducing carbohydrate intake and consuming palatable foods remaining a concern.
“Nowadays there is a great variety of sweeteners, each with different origins and compositions,” Concha said.
“However, our research shows that it is not only a matter of avoiding the addition of calories to the body through a compound. It is also necessary to study the effects on them and on consumers’ offspring.” -- SOUTH CHINA MORNING POST
