Artificial sweeteners linked to abnormal glucose metabolism

Gut bacteria, artificial sweeteners and glucose intolerance
Gut microbiota. Credit: Weizmann Institute of Science

Artificial sweeteners, promoted as aids to weight loss and diabetes prevention, could actually hasten the development of glucose intolerance and metabolic disease; and they do it in a surprising way: by changing the composition and function of the gut microbiota – the substantial population of bacteria residing in our intestines. These findings, the results of experiments in mice and humans, were published today in Nature. Among other things, says Dr. Eran Elinav of the Weizmann Institute's Immunology Department, who led this research together with Prof. Eran Segal of Computer Science and Applied Mathematics Department, the widespread use of artificial sweeteners in drinks and food may be contributing to the obesity and diabetes epidemic that is sweeping much of the world.

For years researchers have been puzzling over the fact that non-caloric do not seem to assist in weight loss, and some studies have suggested they may even have an opposite effect. Graduate student Jotham Suez in Elinav's lab, who led the study, collaborated with graduate students Tal Korem and David Zeevi in Segal's lab and Gili Zilberman-Shapira in Elinav's lab in discovering that artificial sweeteners, even though they do not contain sugar, nonetheless have a direct effect on the body's ability to utilize glucose. Glucose intolerance – generally thought to occur when the body cannot cope with large amounts of sugar in the diet – is the first step on the path to metabolic syndrome and adult-onset diabetes.

The scientists gave water laced with the three most commonly used artificial sweeteners – in the equivalent amounts to those permitted by the FDA. These mice developed , as compared to mice that drank water, or even sugar water. Repeating the experiment with different types of mice and different doses of the sweeteners produced the same results – these substances were somehow inducing glucose intolerance.

Next, the researchers investigated a hypothesis that the gut microbiota are involved in this phenomenon. They thought the bacteria might do this by reacting to new substances like artificial sweeteners, which the body itself may not recognize as "food." Indeed, artificial sweeteners are not absorbed in the gastrointestinal tract, but in passing through they encounter trillions of the bacteria in the gut microbiota.

Gut bacteria, artificial sweeteners and glucose intolerance
Weizmann Institute research shows that artificial sweeteners promote glucose intolerance in a surprising way: by changing the composition and function of the gut microbiota. Credit: Weizmann Institute of Science

The researchers treated mice with antibiotics to eradicate many of their gut bacteria; this resulted in a full reversal of the artificial sweeteners' effects on . Next, they transferred the microbiota from mice that consumed artificial sweeteners to 'germ-free' mice – resulting in a complete transmission of the glucose intolerance into the recipient mice. This, in itself, was conclusive proof that changes to the gut bacteria are directly responsible for the harmful effects to their host's metabolism. The group even found that incubating the microbiota outside the body, together with artificial sweeteners, was sufficient to induce glucose intolerance in the sterile mice. A detailed characterization of the microbiota in these mice revealed profound changes to their bacterial populations, including new microbial functions that are known to infer a propensity to obesity, diabetes and complications of these problems in both mice and humans.

Does the human microbiome function in the same way? Elinav and Segal had a means to test this as well. As a first step, they looked at data collected from their Personalized Nutrition Project, the largest human trial to date to look at the connection between nutrition and microbiota. Here, they uncovered a significant association between self-reported consumption of artificial sweeteners, personal configurations of gut bacteria and the propensity for glucose intolerance. They next conducted a controlled experiment, asking a group of volunteers who did not generally eat or drink artificially sweetened foods to consume them for a week and then undergo tests of their as well as their gut microbiota compositions.

The findings showed that many – but not all – of the volunteers had begun to develop glucose intolerance after just one week of artificial consumption. The composition of their explained the difference: The researchers discovered two different populations of human gut bacteria – one that induced glucose intolerance when exposed to the sweeteners, the second that had no effect either way. Elinav believes that certain bacteria in the guts of those who developed glucose intolerance reacted to the chemical sweeteners by secreting substances that then provoked an inflammatory response similar to sugar overdose, promoting changes in the body's ability to utilize sugar.

Segal: "The results of our experiments highlight the importance of personalized medicine and nutrition to our overall health. We believe that an integrated analysis of individualized 'big data' from our genome, microbiome and dietary habits could transform our ability to understand how foods and nutritional supplements affect a person's health and risk of disease."

Elinav: "Our relationship with our own individual mix of is a huge factor in determining how the food we eat affects us. Especially intriguing is the link between use of artificial sweeteners – through the bacteria in our guts – to a tendency to develop the very disorders they were designed to prevent; this calls for reassessment of today's massive, unsupervised consumption of these substances."

Explore further

Artificial sweeteners may do more than sweeten

More information: Artificial sweeteners induce glucose intolerance by altering the gut microbiota, Nature,
Journal information: Nature

Citation: Artificial sweeteners linked to abnormal glucose metabolism (2014, September 17) retrieved 20 October 2019 from
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Sep 17, 2014
Another great example of injury and death, caused by artificial food ingredients and chemical additives, not seen for decades.
Better living through chemistry? I think Not!

Sep 17, 2014
We can reference http://en.wikiped...bstitute concerning artificial sweeteners. Laboratory made, esp. of the GMO variety, can also contain herbicides and pesticides which negatively affect gut bacteria. Stevia is not an artificial sweetener; although it is listed at Wikipedia, it is more like lo han fruit in terms of natural sweetness, but it is either an extract mixed with a "filler" sweetener like maltodextrin or the whole herb. Xylitol is up in the air as far as its effects on gut bacteria; it depends on the source and the way it's derived - the best source is crystalized extract from birch trees, but most of the xylitol on the market is from corn. Make sure it's non-GMO.

Sep 17, 2014
Does anyone know which sweetners were included in their study?

Sep 17, 2014
Does anyone know which sweetners were included in their study?

"The scientists gave mice water laced with the three most commonly used artificial sweeteners"

To me, that would mean Splenda, Equal, and Sweet&Low.

Sep 18, 2014
Riding on an airplane yesterday reminded me again why more people should lose weight.

Passengers don't fit so well any more? Maybe also due to densification. Airlines exploring the limits of what passengers will endure. Perhaps the density creep will cease once passenger on passenger cannibalism sets in.

Sep 18, 2014
Here's my take on this. I actually read the paper in question. The researchers claim to see an decrease in glucose tolerance between mice who were fed aspartame, saccharine, and sucrolose, and those that were fed sugar. I saw a plot of their data, and I don't see any differences - especially with aspartame. They don't have enough data to rule out natural variability. In addition, when all the mice were fed antibiotics, all of their glucose sensitivities increased - not just those who were fed the artificial sweeteners. The biggest effect on glucose sensitivity seemed to be from the gut bacteria - not what the mice were fed. Also, only saccharine was used in the subsequent experiments where they looked at the gut bacteria, aspartame and sucralose were not studied in this portion of their work. Furthermore, there is no good reason why all three of these chemicals would react the same way in bacteria.

Sep 20, 2014
Thanks, Debbie. Press releases are really marketing tools, rather than an objective assessment of a piece of scientific research. Likewise, quotes from the authors of a paper will generally present the most optimistic interpretation, even if the results are very preliminary. Unfortunately, popular health-related websites often present preliminary observations as though they are the truth.

BTW mice are a valuable and economical tool for conducting basic, exploratory research; however, it's important to validate that they are a predictive model of a particular human disease. The title of news articles like this should always include the word "mice", in my opinion.

Sep 20, 2014
Jim, it probably does not make much difference. The absence of sugar is what is key.

But fresh water does not contain any sugar, yet it did not seem to have the negative effect of artificial sweeteners.

I feel this study is flawed somehow. Not even wasps can taste the sweetness of artificial sweeteners, they have different type of sweet receptors that humans. So how could bacteria have more "human like" sweet receptors than wasps. Also, recently, there was a meta study that showed clearly how people can loose more weight with diet cokes and other artificially sweetened drinks than with plain water, not to mention sugar containing drinks. My personal observation support that as well.

Oct 07, 2014
Apart from stevia and xylitol, trehalose is a very interesting natural sweetener. I'd like to see someone study these.

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