Non-nutritive sweeteners are commonly integrated into human diet and presumed to be inert. However, previous studies suggest that they may impact the microbiome and downstream glycemic responses. In a new randomized-controlled trial, a research team led by Weizmann Institute of Science and the German National Cancer Center scientists assessed the impact of non-nutritive sweeteners — such as saccharin, sucralose, aspartame, and stevia sachets — in humans and their microbiomes. They found that these sugar substitutes are not inert, and, in fact, some can alter human microbiomes in a way that can change their blood sugar levels.
Consumption of non-nutritive sweeteners may induce person-specific, microbiome-dependent glycemic alterations, necessitating future assessment of clinical implications. Image credit: Suez et al., doi: 10.1016/j.cell.2022.07.016.
In 2014, Dr. Eran Elinav from the Weizmann Institute of Science and the German National Cancer Center and colleagues found that non-nutritive sweeteners affected the microbiomes of mice in ways that could impact their glycemic responses.
The researchers were interested in whether these results would also be found in humans.
To address this important question, they screened over 1,300 individuals for those who strictly avoid non-nutritive sweeteners in their day-to-day lives, and identified a cohort of 120 individuals.
These participants were broken into six groups: two controls and four who ingested well below the FDA daily allowances of either aspartame, saccharin, stevia, or sucralose.
“In subjects consuming the non-nutritive sweeteners, we could identify very distinct changes in the composition and function of gut microbes, and the molecules they secret into peripheral blood,” Dr. Elinav said.
“This seemed to suggest that gut microbes in the human body are rather responsive to each of these sweeteners.”
“When we looked at consumers of non-nutritive sweeteners as groups, we found that two of the non-nutritive sweeteners, saccharin and sucralose, significantly impacted glucose tolerance in healthy adults.”
“Interestingly, changes in the microbes were highly correlated with the alterations noted in people’s glycemic responses.”
To establish causation, the authors transferred microbial samples from the study subjects to germ-free mice.
“The results were quite striking,” Dr. Elinav said.
“In all of the non-nutritive sweetener groups, but in none of the controls, when we transferred into these sterile mice the microbiome of the top responder individuals collected at a time point in which they were consuming the respective non-nutritive sweeteners, the recipient mice developed glycemic alterations that very significantly mirrored those of the donor individuals.”
“In contrast, the bottom responders’ microbiomes were mostly unable to elicit such glycemic responses.”
“These results suggest that the microbiome changes in response to human consumption of non-nutritive sweetener may, at times, induce glycemic changes in consumers in a highly personalized manner.”
The scientists expect the effects of the sweeteners will vary person to person because of the incredibly unique composition of human microbiome.
“We need to raise awareness of the fact that non-nutritive sweeteners are not inert to the human body as we originally believed,” Dr. Elinav said.
“With that said, the clinical health implications of the changes they may elicit in humans remain unknown and merit future long-term studies.”
“In the meantime, we need to continue searching for solutions to our sweet tooth craving, while avoiding sugar, which is clearly most harmful to our metabolic health. In my personal view, drinking only water seems to be the best solution.”
The results appear this month in the journal Cell.
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Jotham Suez et al. Personalized microbiome-driven effects of non-nutritive sweeteners on human glucose tolerance. Cell, published online August 19, 2022; doi: 10.1016/j.cell.2022.07.016
