Artificial sweeteners may tip scales toward metabolic problems

In mice and people, saccharin upsets gut microbes, glucose metabolism

artificial sweetener packets

BITTERSWEET  The artificial sweetener saccharin, an ingredient in Sweet'N Low, meddles with the gut’s microbial community, setting in motion metabolic changes associated with obesity and diabetes.

Alex Cameron/Flickr (CC BY-NC-SA 2.0)

Eating artificial sweeteners may spur the very health problems that dieters try to avoid. A new multipronged study of mice and a small number of people finds that saccharin meddles with the gut’s microbial community, setting in motion metabolic changes that are associated with obesity and diabetes.

Other zero-calorie sweeteners may cause the same problems, researchers say September 17 in Nature.

Though the finding is preliminary, four of seven human volunteers eating a diet high in saccharin developed impaired glucose metabolism, a warning sign for type 2 diabetes.

“This is very interesting and scary if it really does hold for humans,” says Robert Margolskee of the Monell Chemical Senses Center in Philadelphia, who was not involved with the work. “There could be unintended consequences of these artificial sweeteners.”

Until recently, most sugar substitutes were thought to pass through the gut undigested, exerting little to no effect on intestinal cells. As ingredients in diet soda, sugar-free desserts and a panoply of other foods, the sweeteners are touted as a way for people with diabetes and weight problems to enjoy a varied diet.

But the new study, led by computational biologist Eran Segal and immunologist Eran Elinav of the Weizmann Institute of Science in Rehovot, Israel, suggests that rather than helping people, the sweeteners may promote problems.

After 11 weeks of drinking water doped with the sweeteners saccharin, sucralose or aspartame, mice had abnormally high glucose levels in their blood after eating. Digested food gets broken down into glucose, the most common carbohydrate, which then enters the bloodstream to be used as fuel or stored, often as fat. When glucose metabolism is impaired, high blood glucose levels — a hallmark of diabetes — can result.

Since blood glucose levels were most off-kilter in the saccharin-fed mice, the researchers zeroed in on this sweetener, which is found in Sweet’N Low, jams, salad dressings, vitamins and many other low- and no-calorie foods. The scientists gave saccharin to mice that were fed a high-fat diet. The mice developed impaired glucose metabolism in as little as five weeks, suggesting the sweetener had the same effect regardless of whether mice were lean or overweight. Meanwhile, mice eating glucose-laced water had normal metabolisms.

microbes on intestinal cells of a mouse
GUT REACTION Stringlike filaments of microbes grow on intestinal cells of a mouse. This microbial community in mice and people can be altered by eating the artificial sweetener saccharin and may prompt metabolic problems. Weizmann Institute of Science
Then the scientists gave the saccharin-fed mice antibiotics to wipe out their intestinal bacteria. The mice’s glucose metabolism recovered, suggesting that gut microbes might play an important role in glucose metabolism. So the researchers transplanted fecal microbes from saccharin-fed mice into the guts of mice with microbe-free intestines that then, in turn, developed impaired glucose metabolism.

Genetic analyses of the microbes in the mice’s intestines revealed major differences in the microbial groups present in saccharin-fed mice compared with mice eating a regular diet.

“This is the home run experiment,” says immunologist Cathryn Nagler of the University of Chicago. “It’s telling you that it is some change in the bacterial community that is detrimental.”

Why the bacterial community shifts is still unknown. Perhaps some bacteria thrive on saccharin and outcompete their neighbors, or maybe the sweetener kills off other bacteria. The mechanisms that disrupt glucose metabolism also remain mysterious. But it’s clear that saccharin doesn’t pass silently through the mouse intestine with no effect.

It also doesn’t pass through people silently, Segal and Elinav’s team suggests. When the researchers looked at 40 people who reported eating artificial sweeteners and compared them to 236 people who did not, the sweetener-eaters were more likely to have had metabolic problems, including impaired glucose metabolism.

And when seven healthy volunteers ate the Food and Drug Administration’s maximum acceptable daily dose of saccharin for a week, four of them developed off-kilter glucose metabolism . Transferring feces from two of these four people into mice induced the same problems in the rodents, suggesting that gut microbes were to blame.

There is much more work to be done to replicate the finding with more people and figure out which bacterial species matter. But, says Nagler, the results are consistent with a bigger picture suggesting that some amenities of the relatively microbe-free modern Western society — such as heavy antibiotic use and cesarean sections — may actually promote disease.

“We have to respect the power of the microbiota,” she says, “We need to step back and see what we are doing.” 

Editor’s Note: This article was updated September 19, 2014, to correct the type of diet (high-fat) that mice were on when they performed the five-week saccharin experiments and the number of people (two) with impaired glucose tolerance whose feces were transferred to mice.

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