Influence of Sweeteners on the Gut Microbiome

1. Gut Microbiome
2. Sugar Substitutes, Sweeteners, and Sugar Alcohols
2.1 Sweeteners
2.2 Sugar Substitutes
3. Studies on the Influence of Sweeteners on the Microbiome
3.1 Saccharin and Sucralose
3.2 Aspartam und Acesulfam-K
4. Sweeteners, Microbiome, and Blood Sugar
5. The Dose Makes the Poison

1. Gut Microbiome

The gut microbiome, also known as the gut flora, refers to the microorganisms living in the intestine. It consists of bacteria, archaea, and fungi, and is a natural part of the human body. The composition of the gut microbiome varies from person to person. There are also compositions that can be classified as either beneficial or harmful. A microbiome deviating from the healthy norm can be associated with certain diseases. Gut bacteria perform numerous tasks, including training and influencing the development of the immune system, producing vitamins, defending against pathogens, and more.

2. Sugar Substitutes, Sweeteners, and Sugar Alcohols

Sugar substitutes or sweeteners is the umbrella term for substances intended to replace sugar in foods. These include sweeteners and sugar alcohols.

2.1 Sweeteners

Sweeteners are also referred to as non-caloric sweeteners (NAS) or non-sugar sweeteners (NSS). Examples of sweeteners include aspartame, advantame, saccharin, stevia, and sucralose. The consumption of sweeteners has become increasingly popular in recent years, especially in the field of body weight control. The Food Association of Germany classifies sweeteners as additives that sweeten foods but, unlike sugar and sugar alcohols, provide no energy [und] and have no impact on blood sugar levels or dental health [haben](1).

2.2 Sugar Substitutes

Here in Germany, a legal distinction is made between sweeteners and sugar alcohols (2). Sugar alcohols or bulk sweeteners include substances like xylitol, erythritol, sorbitol, isomalt, and mannitol (2). The current body of research on the impact of sugar alcohols on the gut microbiome is still rather limited, and no clear conclusions can be drawn at this time.

3. Studies on the Influence of Sweeteners on the Microbiome

Opinions about the increased consumption of sweeteners are divided. There are frequent reports of a negative impact of sweeteners on the gut microbiome.

3.1 Saccharin and Sucralose

A 2014 study showed a change in the gut microbiome composition after chronic sweetener consumption in mice. Particularly, saccharin led to the development of dysbiosis (3).
However, a 2021 study found no changes in microbiota diversity in humans and mice after two weeks of saccharin supplementation (4).
In 2022, researchers from Johns Hopkins University (USA) published a study showing changes in the microbiota after consuming both saccharin and sucralose. Participants consumed the respective sweeteners for 28 days (5).
A 2018 study demonstrated bacteriostatic properties of saccharin and sucralose (6), which could explain their negative influence on the gut microbiome.
A review from 2022 summarized the known research on the effect of saccharin and sucralose on the gut microbiome. While most short-term studies found no negative effects, some long-term studies showed changes in gut microbiota. However, the data from long-term studies is insufficient to draw a clear conclusion (7).
Sucralose is only about 15% absorbed by the human gastrointestinal tract and is then excreted unchanged in urine. This means that 85% of the consumed sucralose reaches the colon and the gut microbiome. However, 94-99% of it is excreted unchanged in the stool, suggesting that sucralose is not metabolized by the gut flora (8).

3.2 Aspartam und Acesulfam-K

Other sweeteners, such as aspartame and acesulfame-K, appear not to come into contact with the gut microbiota and thus cannot influence it (8). However, bacteriostatic properties of acesulfame-K have also been demonstrated (6).

4. Sweeteners, Microbiome, and Blood Sugar

Blood sugar refers to the amount of glucose in the blood. Glucose is an important energy source for our cells. Insulin lowers blood sugar levels by enabling glucose to be taken up by cells, thereby leaving the bloodstream. If there is an insulin deficiency or insulin resistance, not enough glucose enters the cells and remains in the blood. This is known as type 1 or type 2 diabetes mellitus.
The aforementioned study from Johns Hopkins University also examined the glycemic effect of sweeteners and the influence of the gut microbiome (5). The researchers found that the consumption of sucralose, saccharin, and aspartame, when paired with glucose consumption, resulted in a reduced increase in insulin blood levels compared to the intake of glucose alone. This means that with the same amount of sugar consumed, less glucose is absorbed by the cells, leading to a higher blood sugar level when sweeteners are consumed simultaneously. Interestingly, this effect is also influenced by the microbiome. When the researchers transferred the microbiomes of participants who had consumed sweeteners into mice (via stool transplantation), the mice exhibited similarly altered effects on their blood sugar levels after glucose intake (5).
However, it is important to emphasize that the current body of research on the impact of sweeteners on gut bacteria and, subsequently, on blood sugar levels is still relatively sparse as of June 2024, and no clear conclusions can be drawn at this time. Future study results could be intriguing.

5. The Dose Makes the Poison

In summary, the contradictory research findings allow for the following conclusion: The effects of sweeteners on the gut microbiome depend on the type of sweetener, as well as the duration and amount of consumption. As Paracelsus used to say, “The dose makes the poison.” Altogether, it is important to note, that a healthy nutrition is what is also best for the microbiota.

References

1. Süßstoffe: Lebensmittelverband Deutschland; latest check 27.05.2023
2. Bewertung von Süßstoffen und Zuckeraustauschstoffen (bund.de); latest check 04.06.2023
3. Suez J, Korem T, Zeevi D, Zilberman-Schapira G, Thaiss CA, Maza O, Israeli D, Zmora N, Gilad S, Weinberger A, Kuperman Y, Harmelin A, Kolodkin-Gal I, Shapiro H, Halpern Z, Segal E, Elinav E. Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Nature. 2014 Oct 9;514(7521):181-6. doi: 10.1038/nature13793. Epub 2014 Sep 17. PMID: 25231862.
4. Serrano J, Smith KR, Crouch AL, Sharma V, Yi F, Vargova V, LaMoia TE, Dupont LM, Serna V, Tang F, Gomes-Dias L, Blakeslee JJ, Hatzakis E, Peterson SN, Anderson M, Pratley RE, Kyriazis GA. High-dose saccharin supplementation does not induce gut microbiota changes or glucose intolerance in healthy humans and mice. Microbiome. 2021 Jan 12;9(1):11. doi: 10.1186/s40168-020-00976-w. PMID: 33431052; PMCID: PMC7802287.
5. 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 Sep 1;185(18):3307-3328.e19. doi: 10.1016/j.cell.2022.07.016. Epub 2022 Aug 19. PMID: 35987213.
6. Wang QP, Browman D, Herzog H, Neely GG. Non-nutritive sweeteners possess a bacteriostatic effect and alter gut microbiota in mice. PLoS One. 2018 Jul 5;13(7):e0199080. doi: 10.1371/journal.pone.0199080. PMID: 29975731; PMCID: PMC6033410.
7. Del Pozo S, Gómez-Martínez S, Díaz LE, Nova E, Urrialde R, Marcos A. Potential Effects of Sucralose and Saccharin on Gut Microbiota: A Review. Nutrients. 2022 Apr 18;14(8):1682. doi: 10.3390/nu14081682. PMID: 35458244; PMCID: PMC9029443.
8. Plaza-Diaz J, Pastor-Villaescusa B, Rueda-Robles A, Abadia-Molina F, Ruiz-Ojeda FJ. Plausible Biological Interactions of Low- and Non-Calorie Sweeteners with the Intestinal Microbiota: An Update of Recent Studies. Nutrients. 2020 Apr 21;12(4):1153. doi: 10.3390/nu12041153. PMID: 32326137; PMCID: PMC7231174.