Diabetes, Diet, Featured, Metabolic syndrome, Obesity

Artificial sweeteners shown to alter gut microbiome leading to elevated glycemic response 

A recently published study demonstrates the effect non-nutritive sweeteners have on gut microbiota and glucose intolerance. (Image: Clostridia, Flickr/Argonne National Laboratory)

Hyperglycemia, or high blood sugar, is a medical condition that can cause serious health complications if left unmanaged. Several lifestyle factors, including an unbalanced diet, can contribute to hyperglycemia. Non-nutritive sweeteners (NNS) are commonly used to combat obesity and are often included in dietary strategies for weight loss. These sweeteners provide a similar sweet taste to sugar but contain little to no calories.

NNS includes saccharinsucraloseaspartame, acesulfame-K, and stevia. Although these sweeteners are not contributing calorically, many scientists have suggested that they may be altering metabolic processes in other ways.

A research team out of the Weizmann Institute of Science and the German National Cancer Center (DKFZ), has identified a causal link between NNS-related microbiome alterations and impaired glycemic response.

This randomized-controlled trial (RCT) consisted of 120 healthy adults evenly split among six (6) groups. Each group received one of the following treatments for two (2) weeks: saccharin, aspartame, sucralose, stevia, glucose, or no supplementation. The groups receiving NNS supplementation received two (2) standard packets three (3) times per day, ranging from 8%-75% of the acceptable daily intake. The group receiving glucose supplementation received five (5) grams per day. The groups were assessed using continuous glucose monitors, blood tests, and microbiome samples via stool and saliva. The results indicated that both saccharin and sucralose significantly increased glycemic response when compared to glucose (p=0.042, 0.004). Aspartame and stevia did not have a significant effect on glycemic response.

The authors stated, “Taken together, these findings indicate that short-term consumption of sucralose and saccharin in doses lower than the ADI can impact glycemic responses in healthy individuals.” It’s important to highlight that there were no appreciable variations in the groups’ nutritional consumption or levels of physical exercise. 

Longitudinal stool sampling of participants revealed that sucralose and saccharin use resulted in significant functional effects on the gut microbiome when compared to baseline. These effects included alterations in metabolic pathways related to purine metabolism, polyamine metabolism, glycolysis, glucose degradation, and fatty acid synthesis.

Through gut microbe transplantation, the researchers found that the gut microbiome was responsible for the alterations in glycemic response.

The researchers implanted gut microbes in the mice from either day 1 or day 21 of the RCT. The transplanted microbes included those from 42 individuals, including seven (7) from each group— four (4) of the individuals with the greatest glycemic response, and three (3) with the least glycemic response.

The mice who received microbiome transplantations from the final treatment day of the top four (4) responders in both the sucralose and saccharin groups showed significantly higher glycemic responses. Gut microbiome transplantations from three (3) of the top four (4) responders in both the aspartame and stevia groups resulted in significant alterations to glucose tolerance in the mice. No significant changes in glycemic response resulted from the lowest responders’ microbiomes in any group, aside from the saccharin group, which had all three (3) of it’s lowest responders’ microbiomes result in significantly elevated glycemic responses in the mice. 

The authors concluded, “the glycemic responses in the humanized mice largely reflected those of their NNS-supplemented donors and serve as a likely causal link between NNS-related microbiome modulations and disrupted glycemic control.”

The study was published in Cell on August 19th, 2022.

Abstract. Non-nutritive sweeteners (NNS) are commonly integrated into human diet and presumed to be inert; however, animal studies suggest that they may impact the microbiome and downstream glycemic responses. We causally assessed NNS impacts in humans and their microbiomes in a randomized-controlled trial encompassing 120 healthy adults, administered saccharin, sucralose, aspartame, and stevia sachets for 2 weeks in doses lower than the acceptable daily intake, compared with controls receiving sachet-contained vehicle glucose or no supplement. As groups, each administered NNS distinctly altered stool and oral microbiome and plasma metabolome, whereas saccharin and sucralose significantly impaired glycemic responses. Importantly, gnotobiotic mice conventionalized with microbiomes from multiple top and bottom responders of each of the four NNS-supplemented groups featured glycemic responses largely reflecting those noted in respective human donors, which were preempted by distinct microbial signals, as exemplified by sucralose. Collectively, human NNS consumption may induce person-specific, microbiome-dependent glycemic alterations, necessitating future assessment of clinical implications.

Suez J, Cohen Y, Valdés-Mas R, Mor U, Dori-Bachash M, Federici S, Zmora N, Leshem A, Heinemann M, Linevsky R, Zur M, Ben-Zeev Brik R, Bukimer A, Eliyahu-Miller S, Metz A, Fischbein R, Sharov O, Malitsky S, Itkin M, Stettner N, Harmelin A, Shapiro H, Stein-Thoeringer CK, Segal E, Elinav E. Personalized microbiome-driven effects of non-nutritive sweeteners on human glucose tolerance. Cell. 2022 Aug 17:S0092-8674(22)00919-9. doi: 10.1016/j.cell.2022.07.016. Epub ahead of print. PMID: 35987213.

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