Non-Nutritive Sweeteners Can Alter Glycemic Responses and Microbiomes
Author: Cell Press
Published: 2022/08/19 - Updated: 2025/04/08
Publication Details: Peer-Reviewed, Research, Study, Analysis
Topic: Fitness and Nutrition - Publications List
Page Content: Synopsis - Introduction - Main - Insights, Updates
Synopsis: Non-nutritive sweeteners can alter gut microbiomes and glycemic responses, raising concerns about their metabolic effects and implications for personalized health.
Why it matters: This report explores the impact of non-nutritive sweeteners (NNS) on glycemic responses and microbiome composition, challenging the long-standing assumption that these sugar substitutes are metabolically inert. It highlights findings from randomized controlled trials showing that saccharin and sucralose significantly altered glucose tolerance in healthy adults, while all tested sweeteners affected gut microbiome composition and function. The study suggests these effects are highly personalized, mediated by microbiome changes, and could have implications for dietary recommendations, particularly for individuals managing hyperglycemia or metabolic disorders. This information is especially relevant for seniors or people with disabilities who may rely on NNS as part of their dietary management strategies - Disabled World (DW).
Introduction
Personalized microbiome-driven effects of non-nutritive sweeteners on human glucose tolerance.
Since the late 1800s, non-nutritive sweeteners have promised to deliver all the sweetness of sugar with none of the calories. They have long been believed not to affect the human body. Still, researchers publishing in the journal Cell on August 19, 2022, challenge this notion by finding that these sugar substitutes are not inert and some can alter human consumers' microbiomes in a way that can change their blood sugar levels.
Main Item
In 2014, senior author Eran Elinav, an immunologist and microbiome researcher at the Weizmann Institute of Science and the German National Cancer Center (DKFZ), and his team found that non-nutritive sweeteners affected the microbiomes of mice in ways that could impact their glycemic responses. The team was interested in whether these results would be found in humans.
To address this important question, the research team carefully screened over 1300 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 the peripheral blood. This seemed to suggest that gut microbes in the human body are rather responsive to each of these sweeteners," says Elinav.
"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 in people's glycemic responses."

To establish causation, the researchers transferred microbial samples from the study subjects to germ-free mice - mice raised in completely sterile conditions and have no microbiome of their own.
"The results were quite striking," says Elinav. "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," he adds.
"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."
Elinav says that he expects the effects of the sweeteners will vary from person to person because of the incredibly unique composition of our microbiome.
"We need to raise awareness of the fact that non-nutritive sweeteners are not inert to the human body as we originally believed. 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 most harmful to our metabolic health," says Elinav. "I think drinking only water seems to be the best solution."
Cell, Suez et al. "Personalized microbiome-driven effects of non-nutritive sweeteners on human glucose tolerance".
Insights, Analysis, and Developments
Editorial Note: This article brings attention to the overlooked consequences of consuming non-nutritive sweeteners, shedding light on how such substances might alter our physiological responses and gut health. With more people turning to sugar substitutes as a means of managing weight or diabetes, it is crucial to stay informed about their broader health impacts. This article helps fill a gap in understanding and provides essential information for making better dietary decisions - Disabled World (DW).Attribution/Source(s): This peer reviewed publication was selected for publishing by the editors of Disabled World (DW) due to its relevance to the disability community. Originally authored by Cell Press and published on 2022/08/19, this content may have been edited for style, clarity, or brevity. For further details or clarifications, Cell Press can be contacted at cell.com NOTE: Disabled World does not provide any warranties or endorsements related to this article.