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 so 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 September 17 in Nature. Dr. Eran Elinav of the Weizmann Institute of Science's Department of Immunology, who led this research together with Prof. Eran Segal of the Department of Computer Science and Applied Mathematics, says that the widespread use of artificial sweeteners in drinks and food, among other things, 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 artificial sweeteners do not seem to assist in weight loss, with some studies suggesting that they may even have an opposite effect. Graduate student Jotham Suez in Dr. Elinav's lab, who led the study, collaborated with lab member Gili Zilberman-Shapira and graduate students Tal Korem and David Zeevi in Prof. Segal's lab to discover 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 mice water laced with the three most commonly used artificial sweeteners, in amounts equivalent to those permitted by the U.S. Food and Drug Administration (FDA). These mice developed glucose intolerance, as compared to mice that drank water, or even sugar water. Repeating the experiment with different types of mice and different doses of the artificial 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.

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 glucose metabolism. Next, they transferred the microbiota from mice that consumed artificial sweeteners to "germ-free," or sterile, 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.