Some studies (Ahmad et al., 2020; Serrano et al., 2021) have concluded that consumption pf normal amounts of artificial sweeteners such as aspartame, saccharin, or sucralose, does not impact the gastrointestinal microbiota. However, Suez et al. (2014) found the correlation between non-caloric artificial sweetener intake and Enterbacteriaceae, Deltaproteobacteria, and Actinobacteria to be statistically significant, when they looked at rRNA from 172 people. These microbiota populations were not correlated with BMI, so even though the BMIs of those with higher artificial sweetener intake were higher, the differences in microbiota composition between the two groups could not be explained by saying that people with higher BMI are more likely to use artificial sweeteners. They then looked at the change in microbiota for seven people who did not normally consume artificial sweeteners, before and after six days of giving them 120 mg of saccharin three times a day. They took note of the four out of these seven people who exhibited poorer glucose control on this regimen, and found that those four exhibited noticeable differences between their microbiota before and after this six day challenge, whereas the other three people did not exhibit this change in composition. Additionally, within each of these two groups, they noted similarities in microbiota composition both before and after the challenge that were not seen in the other group. They went on to perform fecal transplants from each of the two groups both before and after the challenge into gnotobiotic mice, and found that the level of glucose tolerance of the human donors was transferred into the recipient mice, suggesting that changes to the microbiota play a role in the reduction in glucose tolerance seen with artificial sweetener intake. The fact that, depending on the composition of their microbiota before the challenge, some people’s changed while others’ did not, might shed light on why previous studies had not found an impact, suggesting that future studies should account for differences in baseline microbiota when analyzing their results.
In just such a further study, Suez et al. (2022) performed a randomized controlled trial with 120 people whose food frequency questionnaires did not reveal any non-nutritive sweeteners in their baseline diets. Glucose was given to one of the control groups and nothing at all to a second control group, while 20 of the participants were assigned to each sweetener to be tested. In this study, they were able to analyze the changes in the microbiota to see how they would behave differently after two weeks of daily sweetener intake, at levels below what is considered acceptable. They found that sucralose affected purine metabolism, saccharin impacted glycolysis and glucose degradation, aspartame affected metabolism of polyamines, and stevia impacted fatty acid synthesis. The authors discuss mechanisms whereby some species may be inhibited by the sweeteners, whereas other species may be enabled to multiply. For future studies they suggest looking at longer durations of intake or lower dosages, and also to compare the results in different groups of people according to their macronutrient consumption.
References:
Ahmad, S. Y., Friel, J., & Mackay, D. (2020). The Effects of Non-Nutritive Artificial Sweeteners, Aspartame and Sucralose, on the Gut Microbiome in Healthy Adults: Secondary Outcomes of a Randomized Double-Blinded Crossover Clinical Trial. Nutrients, 12(11).
Serrano, J., Smith, K. R., Crouch, A. L., Sharma, V., Yi, F., Vargova, V., LaMoia, T. E., Dupont, L. M., Serna, V., Tang, F., Gomes-Dias, L., Blakeslee, J. J., Hatzakis, E., Peterson, S. N., Anderson, M., Pratley, R. E., & Kyriazis, G. A. (2021). High-dose saccharin supplementation does not induce gut microbiota changes or glucose intolerance in healthy humans and mice. Microbiome, 9(1), 1–18.
Suez, J., Thaiss, C. A., Maza, O., Shapiro, H., Elinav, E., Halpern, Z., Korem, T., Zeevi, D., Zilberman-Schapira, G., Israeli, D., Zmora, N., Gilad, S., Weinberger, A., Segal, E., Kuperman, Y., Harmelin, A., & Kolodkin-Gal, I. (2014). Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Nature, 514(7521), 181–186.
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., … Elinav, E. (2022). Personalized microbiome-driven effects of non-nutritive sweeteners on human glucose tolerance. Cell, 185(18), 3307–3328.

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