High doses of artificial sweeteners such as saccharin, sucralose and aspartame can change the population of healthy gut bacteria in mice and in some humans, and those changes can affect how well their bodies metabolize sugar, according to a study published Wednesday in the journal Nature.

“We are by no means prepared to make recommendations about the use and dose of sweeteners, but these results should prompt additional study and debate on the massive use of artificial sweeteners,” said Eran Segal, a computational biologist at the Weizmann Institute of Science in Israel and a senior author of the paper.

Artificial sweeteners are not digested by the human body, which is why they have no calories. However, they still must pass through our gastrointestinal tract, where they encounter the vast ecosystem of bacteria that thrive in our guts. These bacteria, though not technically part of our bodies, still play an important role in our physiology, including how we process glucose and other sugars.

The scientists added saccharine, sucralose or aspartame to the drinking water of different groups of mice. Other mouse groups got the real sugars glucose or sucrose (a combination of glucose and fructose) in their water, and a control group got plain, unsweetened water. After 11 weeks, the mice that received the artificial sweeteners showed higher levels of glucose intolerance compared with the others. (Among other things, this causes blood sugar to be too high, and is often a precursor to Type 2 diabetes).

The researchers saw the same result when the experiment was run on mice that were fed a high-fat diet, a model of what happens when people rely on artificial sweeteners to help them lose weight (or at least gain less weight).