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The Unexpected Health Impacts of Common Sugar Substitutes

Non-nutritive sweeteners, commonly known as artificial sweeteners, promise the sweetness of sugar without the extra calories
Non-nutritive sweeteners, commonly known as artificial sweeteners, promise the sweetness of sugar without the extra calories. (CREDIT: Creative Commons)


Non-nutritive sweeteners, commonly known as artificial sweeteners, promise the sweetness of sugar without the extra calories. However, a recent study by the Weizmann Institute of Science, published in Cell, challenges the notion that these sweeteners are harmless. The research reveals that these sugar substitutes can significantly impact the human body, particularly by altering the gut microbiome, which can affect blood sugar levels in unique ways for different individuals.


Back in 2014, the Weizmann Institute found in a mouse study that some non-nutritive sweeteners might influence sugar metabolism, contrary to their intended purpose.


 
 

Building on this, the new study aimed to explore these effects in humans. Professor Eran Elinav from the Systems Immunology Department led this research, which involved nearly 1,400 candidates. From this pool, 120 individuals who did not consume any artificially sweetened products were chosen for the trial.


(l-r) Yotam Cohen and Prof. Eran Elinav

The participants were divided into six groups. Four groups received sachets containing one of four common sweeteners—saccharin, sucralose, aspartame, or stevia—in amounts below the acceptable daily intake. The remaining two groups served as controls, receiving no sweeteners.


 
 

Dr. Jotham Suez, now a principal investigator at the Johns Hopkins University School of Medicine, along with Yotam Cohen, a graduate student, co-led the research in collaboration with Professor Eran Segal from Weizmann’s Computer Science and Applied Mathematics and Molecular Cell Biology Departments.


After two weeks, the researchers observed that all four sweeteners had altered the composition and function of the participants' gut microbiomes, each in a distinct way.


 

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Particularly, saccharin and sucralose significantly disrupted glucose tolerance, which is the body's ability to manage blood sugar effectively. This disruption in glucose metabolism can contribute to metabolic diseases.


“These findings reinforce the view of the microbiome as a hub that integrates the signals coming from the human body’s own systems and from external factors such as the food we eat, the medications we take, our lifestyle and physical surroundings,” said Elinav.


 
 

To further understand if these microbiome changes directly caused the impaired glucose tolerance, the team conducted a follow-up experiment. They transplanted gut microbes from 40 trial participants into groups of germ-free mice. These mice had never consumed non-nutritive sweeteners before. The human donors included “top responders,” who showed the most significant changes in glucose tolerance, and “bottom responders,” who showed the least changes.


Changes in the composition and function of gut microbes were observed in all four groups of trial participants who consumed non-nutritive sweeteners
Changes in the composition and function of gut microbes were observed in all four groups of trial participants who consumed non-nutritive sweeteners. (CREDIT: Weizmann Institute of Science)

Strikingly, the recipient mice mirrored the glucose tolerance patterns of their human donors. Mice receiving microbiomes from “top responders” experienced the most significant alterations in glucose tolerance, compared to those receiving microbiomes from “bottom responders” and human controls.


 
 

The study also examined how each sweetener influenced the prevalence and function of specific gut bacteria and the small molecules these bacteria released into the bloodstream. The results showed that non-nutritive sweeteners affect glucose responses by modifying the microbiome in a personalized manner, with each person's unique microbiome composition leading to different impacts.



“Our trial has shown that non-nutritive sweeteners may impair glucose responses by altering our microbiome, and they do so in a highly personalized manner,” said Elinav. “In fact, this variability was to be expected, because of the unique composition of each person’s microbiome.”


 
 

Despite these findings, Elinav emphasized that the health implications of these changes are still uncertain. More long-term studies are needed to fully understand the effects. He also pointed out that the study does not suggest that sugar, known for its harmful health impacts, is better than non-nutritive sweeteners.


This groundbreaking study underscores the complexity of the relationship between non-nutritive sweeteners and our bodies. It reveals that these sweeteners, once thought to be harmless, can have significant effects on our microbiome and blood sugar levels. These findings highlight the need for personalized approaches in understanding and managing our diets and health.


As research continues, it remains crucial to consider the broader impact of what we consume on our overall well-being.


 
 

Study participants included Dr. Rafael Valdés-Mas, Uria Mor, Dr. Mally Dori-Bachash, Dr. Sara Federici, Dr. Niv Zmora, Dr. Avner Leshem, Dr. Melina Heinemann, Raquel Linevsky, Maya Zur, Rotem Ben-Zeev Brik, Aurelie Bukimer, Shimrit Eliyahu Miller, Alona Metz, Ruthy Fischbein, Olga Sharov and Dr. Hagit Shapiro from Elinav’s lab; Drs. Sergey Malitsky and Maxim Itkin from Weizmann’s Life Sciences Core Facilities Department; Dr. Noa Stettner and Prof. Alon Harmelin from Weizmann’s Veterinary Resources Department; and Dr. Christoph K. Stein-Thoeringer from the Microbiome & Cancer Division, German Cancer Research Center (DKFZ).







For more science and technology stories check out our New Discoveries section at The Brighter Side of News.


 

Note: Materials provided above by The Brighter Side of News. Content may be edited for style and length


 
 

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