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The study demonstrates that non-nutritive sweeteners have an effect on the human body.

According to a controlled experiment, these sugar substitutes have a variety of impacts on peoples gut microbes and glucose metabolism.

Artificial sweeteners and sugar replacements, also referred to as non-nutritive sweeteners, claim to provide all the sweetness of sugar without the calories. However, contrary to popular assumption, such sweeteners are not inert: They do have an impact on the human body, according to a controlled trial conducted by Weizmann Institute of Science researchers and published in the journal Cell.

In fact, some can influence the trillions of microorganisms that reside in our guts and regulate our blood sugar levels by altering the microbiomes of human consumers. Furthermore, different individuals respond to sweeteners in very different ways.

A Weizmann Institute study on mice conducted in 2014 revealed that certain non-nutritive sweeteners could be causing the alterations in sugar metabolism that they are meant to prevent. A team of researchers led by Professor Eran Elinav of Weizmanns Systems Immunology Department screened roughly 1,400 prospective volunteers in the new experiment, choosing 120 who carefully avoided any artificially sweetened foods or beverages.

Six groups were then formed out of the volunteers. Participants in four of the groups received sachets containing one of the following sweeteners: saccharin, sucralose, aspartame, or stevia, each in quantities that were below the recommended daily consumption. The two other groups acted as controls.

The research was led by Dr. Jotham Suez, a former graduate student of Elinavs who is now a principal investigator at the John Hopkins University School of Medicine, and Yotam Cohen, a graduate student in Elinavs lab. It was carried out in partnership with Professor Eran Segal of Weizmanns Computer Science and Applied Mathematics and Molecular Cell Biology Departments.

The researchers found that two weeks of consuming all four sweeteners changed the composition and function of the microbiome and of the small molecules the gut microbes secrete into peoples blood each sweetener in its own way. They also found that two of the sweeteners, saccharin, and sucralose, strongly altered glucose tolerance that is, proper glucose metabolism in the recipients. Such alterations, in turn, could contribute to metabolic disease. In contrast, no changes in either the microbiome or glucose tolerance were found in either of the two control groups.

The changes in gut microbes caused by sweeteners were strongly associated with changes in glucose tolerance. These findings reinforce the view of the microbiome as a hub that integrates the signals coming from the human bodys own systems and from external factors such as the food we eat, the medications we take, our lifestyle and physical surroundings, Elinav says.

To check whether changes in the microbiome were indeed responsible for impaired glucose tolerance, the researchers transplanted gut microbes from more than 40 trial participants into groups of germ-free mice that had never consumed non-nutritive sweeteners. In each trial group, the transplants had been collected from several top responders (trial participants featuring the biggest changes in glucose tolerance) and several bottom responders (those featuring the least changes in glucose tolerance).

Strikingly, recipient mice showed patterns of glucose tolerance that largely reflected those of the human donors. Mice that received microbiomes from the top responders had the most pronounced alterations in glucose tolerance, compared to mouse recipients of microbiomes from bottom responders and from human controls. In follow-up experiments, the researchers determined how the different sweeteners affected the abundance of specific species of gut bacteria, their function, and the small molecules they secrete into the bloodstream.

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, that is, by affecting each person in a unique way, Elinav says. In fact, this variability was to be expected, because of the unique composition of each persons microbiome.

Elinav continues: The health implications of the changes that non-nutritive sweeteners may elicit in humans remain to be determined, and they merit new, long-term studies. In the meantime, its important to stress that our findings do not imply in any way that sugar consumption, shown to be deleterious to human health in many studies, is superior to non-nutritive sweeteners.

Reference: Personalized microbiome-driven effects of non-nutritive sweeteners on human glucose tolerance by Jotham Suez, Yotam Cohen, Rafael Valds-Mas, Uria Mor, Mally Dori-Bachash, Sara Federici, Niv Zmora, Avner Leshem, Melina Heinemann, Raquel Linevsky, Maya Zur, Rotem Ben-Zeev Brik, Aurelie Bukimer, Shimrit Eliyahu-Miller, Alona Metz, Ruthy Fischbein, Olga Sharov, Sergey Malitsky, Maxim Itkin, Noa Stettner, Alon Harmelin, Hagit Shapiro, Christoph K. Stein-Thoeringer, Eran Segal and Eran Elinav, 19 August 2022, Cell.DOI: 10.1016/j.cell.2022.07.016

The study was funded by the Jeanne and Joseph Nissim Center for Life Sciences Research, the Swiss Society Institute for Cancer Prevention Research, the Sagol Institute for Longevity Research, the Sagol Weizmann-MIT Bridge Program, the Norman E Alexander Family M Foundation Coronavirus Research Fund, the Leona M. and Harry B. Helmsley Charitable Trust, the Rising Tide Foundation, Mike and Valeria Rosenbloom Foundation, the Adelis Foundation, the Ben B. and Joyce E. Eisenberg Foundation, the Isidore and Penny Myers Foundation, Miel de Botton, the Vainboim Family, and Charles S. Rothschild.

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