Artificial Sweeteners and the Microbiome: A Deeper Look at Their Potential Impact

Artificial sweeteners have become an increasingly popular product as alternatives to sugar. We often find them in products that are labelled as "zero" or advertised as sugar-free. Artificial sweeteners are produced through chemical processes that modify naturally occurring compounds or combine specific chemical structures to create the sweet taste.

They contain little to no calories and are significantly sweeter than regular sugar, and hence, smaller amounts are already enough to achieve a sweet taste. (1, 2)

Examples of artificial sweeteners include:

• Aspartame

• Sucralose

• Saccharin

Artificial sweeteners generally do not produce the rapid increase in blood glucose levels observed following sugar consumption. They are therefore often used in weight management and diabetes management, although the evidence is mixed. (2)

However, questions remain regarding their long-term effects on health. One particular area of interest is gut health and whether artificial sweeteners may potentially alter the gut microbiome or its function in ways that affect our health.

While previous literature in mouse models demonstrated microbial changes (3), human intervention studies have produced mixed findings. This article will examine what some of the literature in human trials has reported on artificial sweetener intake and potential impacts on the gut microbiome.

What does the evidence say?

• A randomised controlled trial with 34 healthy males administered 780mg of sucralose per day for seven days to the intervention group and a placebo to the control group. The researchers found no microbiome differences that could be attributed to the use of sucralose. Instead, participants with a higher insulin response appeared to have a pre-existing microbiome structure that is associated with poorer metabolic health. (4)

• Similarly, a crossover study from 2020 included 17 participants and administered realistic doses of aspartame and sucralose for 14 days and also found no changes in microbiota structure after the intervention with either sweetener. (5)

• In a mixed human and mouse study from 2021, the participants consumed saccharin for 14 days at the acceptable daily intake level, and the authors concluded that sweetener intake did not alter the gut microbiome. However, the author noted that while these findings are clear for short-term trials, the long-term effects may differ. (6)

• In contrast, a study from 2022 used aspartame, saccharin, sucralose, and stevia as the intervention in a four-arm randomised controlled trial for 14 days. Distinct alterations in microbiome composition were observed in all four groups, while saccharin and sucralose were most clearly associated with an impaired glycaemic response, although the magnitude and physiological significance of these changes remain uncertain. (7)

• This is further supported by another study from 2022 that used sucralose as the intervention for 10 weeks. The researchers reported shifts in the abundance of certain bacterial taxa, including members of the Firmicutes phylum, following sucralose consumption. However, because this was an open-label trial that assessed a limited set of bacterial targets, the findings should be interpreted cautiously. (8)

What does this mean in practice?

• The relationship between artificial sweeteners and the gut microbiome is complex. Several studies found no measurable changes in gut microbial composition, whereas a smaller number reported alterations in microbial composition, metabolomic profiles, or glycaemic responses.

• Most studies discussed have been short-term studies lasting between one and ten weeks. As a result, the long-term effects of habitual artificial sweetener consumption on the gut microbiome remain largely unknown.

• While some evidence suggests that artificial sweeteners may influence gut microbial communities under certain conditions, current research does not support the conclusion that moderate consumption consistently causes harmful alterations to the gut microbiome.

• Potential negative effects may depend on a combination of factors, including dosage, individual microbiome characteristics, dietary patterns, and overall metabolic health.

Key takeaway

While some studies reported changes in microbial composition, others did not find that artificial sweeteners consistently affect the microbiome. Longer and better-powered studies are needed to further explore potential impacts. Overall dietary quality and lifestyle factors are likely to have a far greater impact on gut health than occasional consumption of artificially sweetened products.

References:

1. Magnuson BA, Carakostas MC, Moore NH, Poulos SP, Renwick AG. Biological fate of low-calorie sweeteners. Nutr Rev. 2016;74(11):670-689. doi:10.1093/nutrit/nuw032.

2. Sylvetsky AC, Rother KI. Nonnutritive sweeteners in weight management and chronic disease: a review. Obesity (Silver Spring). 2018;26(4):635-640. doi:10.1002/oby.22139.

3. Suez J, Korem T, Zeevi D, Zilberman-Schapira G, Thaiss CA, Maza O, et al. Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Nature. 2014;514(7521):181-186. doi:10.1038/nature13793.

4. Thomson P, Santibañez R, Aguirre C, Galgani JE, Garrido D. Short-term impact of sucralose consumption on the metabolic response and gut microbiome of healthy adults. Br J Nutr. 2019;122(8):856-862. doi:10.1017/S0007114519001570.

5. Ahmad SY, Friel J, Mackay D. 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. 2020;12(11):3408. doi:10.3390/nu12113408.

6. Serrano J, Smith KR, Crouch AL, Sharma V, Yi F, Vargova V, et al. High-dose saccharin supplementation does not induce gut microbiota changes or glucose intolerance in healthy humans and mice. Microbiome. 2021;9(1):11. doi:10.1186/s40168-020-00976-w.

7. Suez J, Cohen Y, Valdés-Mas R, Mor U, Dori-Bachash M, Federici S, et al. Personalized microbiome-driven effects of non-nutritive sweeteners on human glucose tolerance. Cell. 2022;185(18):3307-3328.e19. doi:10.1016/j.cell.2022.07.016.

8. Méndez-García LA, Bueno-Hernández N, Cid-Soto MA, De León KL, Mendoza-Martínez VM, Espinosa-Flores AJ, et al. Ten-week sucralose consumption induces gut dysbiosis and altered glucose and insulin levels in healthy young adults. Microorganisms. 2022;10(2):434. doi:10.3390/microorganisms10020434.

Disclaimer: This article is for educational purposes only and does not replace medical advice. Individual needs vary, and personalised guidance from a qualified healthcare professional is recommended for tailored support.