Compounds like saccharin are potent sweeteners, but new research suggests they could be a bitter pill for some gut microbes.

Compounds like saccharin are potent sweeteners, but new research suggests they could be a bitter pill for some gut microbes.


Artificial sweeteners may contribute to diabetes, controversial study finds

When it comes to the sweet stuff, science often turns sour. Almost every study that has linked sugar to problems such as tooth decay, diabetes, obesity, or even childhood violence has come under heavy fire. Nonetheless, the World Health Organization released draft guidelines earlier this year that halved the recommended maximum sugar intake.

Now, new research is suggesting that synthetic sweeteners like saccharin might not be a great alternative. They could have a negative effect on gut microbes and thus lead to a higher risk of diabetes, researchers say. But other scientists say the results fly in the face of previous research and may be wrong. “It would be unfortunate if this data were to influence public policy,” says endocrinologist Stephen O’Rahilly, who heads the metabolic research laboratories at the University of Cambridge in the United Kingdom.

Scientists are only beginning to understand what role the billions of microbial cells colonizing the human gut play in diet and disease. Some microbial boarders are known to be crucial in breaking down nutrients in our diet. Studies have also shown that overweight people tend to have different bacteria in their intestines than slim people, but it is not clear what exactly the link is and whether the bacteria somehow cause obesity or diabetes.

Scientists at the Weizmann Institute of Science in Rehovot, Israel, started by feeding mice with water that contained either sugar or one of three noncaloric sweeteners: aspartame, sucralose, or saccharin. After 11 weeks, the mice fed with artificial sweeteners showed an unusually high spike in blood glucose levels when given a glucose meal, a condition called glucose intolerance that is seen as an early stage in the development of diabetes. But when the mice were given antibiotics for 4 weeks, glucose intolerance didn't occur, indicating that gut microbes may play a role.

The researchers also found that certain types of gut microbes were more common in mice fed saccharin. By transferring the intestinal bacteria from these mice to germ-free mice, the researchers also transferred their glucose intolerance. They even took gut bacteria from healthy mice, cultured them in the laboratory with saccharin, and then transferred them into germ-free mice and showed that these mice, too, developed glucose intolerance. Molecules produced by some of the bacteria may increase glucose production in the body and push blood glucose levels out of balance, the researchers suggest.

To confirm that their findings are relevant to humans as well, the researchers followed seven individuals given a high dose of saccharin—5 milligrams per kilogram of body weight, the Food and Drug Administration’s maximum acceptable daily intake—on 6 consecutive days. Four of these individuals also began showing signs of glucose intolerance, the researchers report online today in Nature, suggesting that artificial sweeteners "may have directly contributed to enhancing the exact [diabetes] epidemic that they themselves were intended to fight.”

It’s "really fascinating work," writes Peter Turnbaugh, a microbiologist at Harvard University, in an e-mail. "There have been some hints in the literature that sweeteners may alter the gut microbiota, but this is by far the most in-depth analysis I've seen to date.” Still, he adds, "there's a lot more basic biology that will need to be worked out to fully appreciate the mechanisms that cause sweeteners to alter gut microbial community composition and function, and how in turn this shapes host metabolism.”

Michael Blaut, a microbiologist at the German Institute of Human Nutrition in Potsdam, Germany, says the mouse data are "believable and remarkable,” but says he has a hard time imagining a mechanism that would account for three compounds as chemically different as aspartame, saccharin, and sucralose leading to the same changes in the gut microbiome.

Others, however, are much more critical. “On this evidence, I'd agree that lab mice shouldn't have lots of sweeteners in their drinking water,” writes Catherine Collins, a dietitian at St. George’s Hospital in London,  in a statement distributed by the Science Media Centre. Lab mice get a much lower part of their calories from carbohydrates than humans do, she points out. “Our naturally higher carbohydrate intake has generated bowel bacteria happily digesting whatever we swallow, and their symbiotic relationship with our bowel cells and beyond is testimony to this.”

The data on humans, from just seven people, of which four show an effect, are far from convincing, O’Rahilly says. "If this had been sent to a clinical research journal there would have been a lot of questions.” Previous research also seems to point in a different direction. A large epidemiological study involving tens of thousands of people published last year found a connection between sugar-sweetened beverages and diabetes, but not between artificially sweetened soft drinks and diabetes.

"We are the first to admit that the human arm in the study has only preliminary results on a small subset of individuals,” says computational biologist Eran Segal, one of the study authors. But some studies in the past also found an association between artificial sweeteners and risk of diabetes, he says. "The lack of conclusive data and a mechanism in such an important subject was at the basis of us looking into this subject."

One possible explanation for the discrepancy with large-scale epidemiological studies is that the new study centers on saccharin, a sweetener not used in any of the major soft drinks. In early studies, the researchers also tested aspartame—by far the most widely used soft drink sweetener—but the observed effect was smaller, and they dropped it. "The authors are confounding their conclusions by addressing all these noncaloric artificial sweeteners together,” says Brian Ratcliffe, a nutrition researcher at Robert Gordon University in Aberdeen, U.K. That's why the title of the paper, “Artificial sweeteners induce glucose intolerance by altering the gut microbiota,” is misleading, he says. "I cannot believe the journal allowed that title.” Still, he says, the data "certainly does suggest that there is something more that needs to be explored about saccharin."

In the meantime, the study shouldn't keep people from lowering their sugar intake by choosing artificially sweetened beverages, says Jim Mann, a researcher at the University of Otago, Dunedin, in New Zealand. "We have always known that artificial sweeteners don’t help everybody lose weight, but they are certainly helpful for some people,” he says. And Mann has another tip: "Water is a very useful way of quenching thirst.”