Artificial Sweeteners contribute to glucose intolerance by altering the Microbiome

Artificial sweeteners are sugar substitutes that provide the sweet taste of sugar, while containing significantly fewer calories. By now, there are at least 10 FDA-approved artificial sweeteners that are commonly added to our food and to diet drinks.
Originally, it was thought that those substances just pass through us, and therefore being a healthy replacement of normal sugar. However, several studies have now shown that artificial sweeteners are not just “inert” substances but can impact our health. [1, 2, 3]

 
thumbnail Artificial sweetener and the microbiome-04.png
 

One mechanism how artificial sweeteners affect our health is via our gut microbiome. A study published in the journal Nature shows how the consumption of commonly used artificial sweeteners can drive the development of type 2 diabetes by altering our gut microbiome. [4]
It is important to note that most artificial sweeteners pass through the stomach without being digested and thus encounter the intestinal microbiome. Therefore, Dr. Eran Elinav and his team set out to investigate the impact of artificial sweeteners on the microbiome and by extension on our health. 

Effect of artificial sweeteners in animals

To analyze the impact of artificial sweeteners on glucose metabolism, they fed mice either the artificial sweeteners saccharin, sucralose or aspartame or as controls water, glucose or sucrose for about 11 weeks. To simulate the real-world situation the researcher stick to the FDA-defined acceptable daily intake on artificial sweeteners and found that all mice groups consuming the artificial sweeteners developed glucose intolerance, which is the hallmark of type 2 diabetes.

Glucose intolerance in mice fed a diet rich in the artificial sweetener Saccharin [Figure 1C]

Glucose intolerance in mice fed a diet rich in the artificial sweetener Saccharin [Figure 1C]

To see whether the gut microbiome has something to do with it, the researchers treated half of the mice of each group with broad-spectrum antibiotics to deplete the microbiome but kept them on the same supplementing regime. Interestingly, after another 4 weeks, the glucose intolerance in the antibiotic-treated mice was abolished, suggesting that the microbiome has something to do with it.

 
Glucose intolerance was reduced in mice treated with antibiotics [Figure 1D]

Glucose intolerance was reduced in mice treated with antibiotics [Figure 1D]

 

The researchers went another step further and performed faecal microbiota transplantations, which basically transfers the microbiome of one mice or person into another. As donors, they used germ-free mice, that is, mice without a microbiome. The mice that received the microbiome from mice that consumed artificial sweeteners developed glucose intolerance after just 6 day, while the control group showed no negative outcome.

Germ-Free mice who received the microbiome from mice that consumed saccharin developed glucose intolerance

Germ-Free mice who received the microbiome from mice that consumed saccharin developed glucose intolerance

The researchers also looked at the microbiome composition of the mice and found that the artificial sweeteners-consuming mice had a very different microbiome than the glucose-consuming mice. The scientist observed an actual dysbiosis in the artificial sweeteners group and certain beneficial bacteria (Lactobacillus reuteri or Akkermansia muciphila) were extremely reduced.

Levels of short-chain fatty acids (SCFAs), which are produced by the gut microbiome were increased in mice who consumed artificial sweeteners, but only the SCFAs acetate and propionate but not butyrate - something that is commonly seen people suffering from metablic disorders.

Effect of artificial sweeteners in humans

Studies in animals usually give you a good idea of what is going on, but confirming hypothesis in humans is always critical.
To do this, the scientist obtained data from an ongoing clinical nutritional study comparing non-artificial sweeteners consumers with high-artificial sweeteners consumer and found that the people who consumed a lot of artificial sweeteners had significantly higher HbA1C levels, which is a marker for the average blood glucose levels over about 3 months.

Levels of HbA1C [%} in non-artiticial sweeteners consumers (Non-Nas consumers) and high-artificial sweeteners consumers (high-NAs consumers) [figure 4a]

Levels of HbA1C [%} in non-artiticial sweeteners consumers (Non-Nas consumers) and high-artificial sweeteners consumers (high-NAs consumers) [figure 4a]

However, it is important to note that some people who didn’t consume artificial sweeteners also had very high glucose levels and that artificial sweeteners are commonly consumed by overweight people that might be already glucose intolerant.
To overcome this observational bias, the scientist followed seven healthy volunteers who usually don’t consume artificial sweeteners. For one week, the participants consumed the FDA’s maximal acceptable daily intake of the artificial sweetener saccharin, which is equivalent to approximately three cans of diet coke and monitored their glucose levels continuously. Even after this short-term exposure, 4 out of the 7 individuals developed poorer glycaemic responses.

Glycaemic response to carbohydrates in the seven volunteers [figure 4b]

Glycaemic response to carbohydrates in the seven volunteers [figure 4b]

Notably, the individual and average microbiome of these four were significantly different than the microbiome of the three people that didn’t show a poorer glycaemic response.
Transferring the microbiome of the four individuals into germ-free mice also induced significant glucose intolerance, while the microbiome from the three people who weren’t affected by artificial sweeteners did not change the glyceamic response to carbohydrates in mice.

This study nicely shows that artificial sweeteners might actually contribute to the obesity epidemic rather than fighting it and that the actual effect of artificial sweeteners on our health might depend on the individual microbiome. At least, we should be aware of this when consuming diet drinks and don’t assume that they do nothing in our bodies.

Follow us on Youtube

References

  1. Pepino et al., Sucralose Affects Glycemic and Hormonal Responses to an Oral Glucose Load, Diabetes Care, 2013

  2. Santos et al., Metabolic effects of aspartame in adulthood: A systematic review and meta-analysis of randomized clinical trials, Crit Rev Food Sci Nutr. 2018

  3. Hill et al., The effect of non-caloric sweeteners on cognition, choice, and post-consumption satisfaction, Appetite, 2014

  4. Suez et al., Artificial sweeteners induce glucose intolerance by altering the gutmicrobiota, Nature, 2014