The bitter truth of artificial sweeteners: the relationship between sugar substitutes and gut health

Sugary beverages and most snacks are loaded with sugar, but let us face reality, they are delicious!

However, if we plan to reduce our sugar consumption, or rather tend to cut those goodies completely for weight loss purposes, our go-to substitute becomes the products labeled as “Sugar-free”!
What we never pay attention to are what is used as a substitute and what health consequences can they result in? Do those artificial sweeteners affect glucose intolerance? What about the gut microenvironment? And finally, are they really healthier than sugars after all?

Since we will discuss the digestive system, let us revise the intestine. This organ is doing its best to absorb as many nutrients as possible from our food/ drink intake. A fascinating aspect of it is the microbiome, which consists of a mixture of bacteria, viruses, immune cells, and other cells that usually reside there. In fact, the microbiome helps in the digestive process, such as breaking sugar and other food particles that did not break completely earlier in the digestive process. Additionally, it fights against foreign particles in the intestine (including viruses and bacteria) and can communicate with other parts of our body, including the brain.

Most of the studies that were trying to understand the effect of the artificial sweeteners were limited, mainly because these groups performed the gene sequencing of the microbiome, which minimized the study of their actual function and their effect on the gut health.

For that, different research groups from Israel, Germany, and the USA looked through a couple of commonly used Non-Nutritive Sweeteners (NNS) – aspartame, saccharin, sucralose, and stevia – to study their effect on human metabolic health and the microbiome.

Each NNS was diluted using glucose as a bulking agent to fit within the accepted daily food intake. They engaged 120 healthy participants in the study, and those were further divided into six groups. Four groups were fed different NNS, the fifth group represented the negative control who were not given any NNS or glucose, and the sixth group representing the positive control was only given glucose solution.

To conduct this experiment correctly, some things needed to be done before, during, and after the experiment. The following steps are how they mainly planned for the study:

• The researchers recorded everyone’s measurements for the metabolic and microbial parameters (as it will act as the baseline).
  Each group measured their corresponding sugars for 28 days.
• The glucose tolerance test (GTT) was performed to examine how the body is responding to the glucose.
• The volunteers were checked for the effect of sweeteners on the gut and oral microbiome; to decide whether the sweeteners will alter their typical dynamic.
• Finally, the fecal microbiome of the volunteers was transferred to germ-free mice models to assess what changes could occur and to look at the glycemic response.

Results from this study were significant in proving that NNS may affect the microbiome, but it also declared that within each group, there were two types of responders. The top responders, whose microbiome immensely reacted towards the NNS, while the bottom responders had weak reactions.

Let’s expand on the GTT results. All groups were challenged with glucose after the second week of NNS exposure. Although the insulin levels were normal, the two groups who consumed saccharin and sucralose had higher blood glucose levels. In contrast, aspartame and stevia showed no changes.

On taking a sample from each participant, they detected that the gut microbiome function had changed in all four groups. Still, both saccharin and sucralose affected the gut microbiome composition the most. Similarly, for the oral microbiome, NNS affected their abundance and altered functions such as sugar degradation and metabolism.

To look even deeper into the microbiome level, they took a fecal sample of 3 top and bottom responders of the sucralose group and implanted them in germ-free mice. Although there was no significant difference between the top and bottom responders in their glycemic response, the outcome was a surprise. It revealed that NNS altered the way microbiomes degraded sugar, such as sucrose and glycogen. This suggests that NNS affects the microbiome, regardless of what the insulin test may show.

The study, however, needs more comprehensive tests with wider and more diverse populations, primarily because it was performed only on healthy, average-weight people. Also, the addition of glucose to NNS could have affected the results slightly.

As NNS affects bacteria within the microbiome, does that mean it will raise a problem in our immune system?
To answer this question, a group in the United States studied the correlation between saccharin intake and inflammatory genes using mice models.
The results suggested that regular saccharin intake in mice would alter some genes in bacteria which are responsible for regulating intestinal metabolites, thus destroying the gut homeostasis by promoting the expression of inflammatory genes in mouse intestine, and simultaneously decreasing the anti-inflammatory ones. Therefore, inflammatory cytokines such as tumor necrosis factor could increase in the liver, thus triggering liver inflammation.

Even though this study was performed only in mice, it raises a red flag for how vital homeostasis is within the gut microbiome.

Nonetheless, be aware that not all humans respond the same, and I am only putting the results of hard-working researchers within your reach. Additionally, as a take-home message, let’s keep in mind two things; first, balance is the key, and second, this Arabic quote: “Too much of a thing brings about its downfall.”

Sources:

• 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.
• Bian X, Tu P, Chi L, Gao B, Ru H, Lu K. Saccharin induced liver inflammation in mice by altering the gut microbiota and its metabolic functions. Food Chem Toxicol. 2017 Sep;107(Pt B):530-539. doi: 10.1016/j.fct.2017.04.045. 

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