Evidence continues to accumulate that sugar is a sweet road to obesity, diabetes, Alzheimer’s, and other maladies. As the dangers of sugar have unfolded there has been an increase in the production and consumption of sugar substitutes, five of which are currently FDA-approved. A recent study published in Nature adds to a growing set of concerns about these artificial sweeteners by presenting evidence that they, like sugar, can cause diabetes as well. The Israel-based research team presented evidence that artificial sweeteners cause this outcome by disrupting the balance of microbes that live in the body’s gut.

This isn’t the first study implicating sugar substitutes with metabolic issues. Research at Purdue University found that saccharin consumption can lead to weight gain in mice by interfering with their ability to control their appetites. Multiple studies have shown that some artificial sweeteners can mess with the body’s endocrine system, and lead to insulin resistance. Many links between the consumption of artificial sweeteners and type 2 diabetes have been uncovered as well, and studies have also shown that consumption of artificial sweeteners can change the way the body deals with food that contains actual calories.

The link between artificial sweeteners, gut bacteria and obesity has been charted as well, in a Duke University study that found that Splenda (sucralose) reduces the amount of ”good bacteria” in the intestines, increases the intestinal pH level, and leads to increased body weight.

The new Nature study moves this ball of research forward by demonstrating that several artificial sweeteners, not just sucralose, can mess with our gut bacteria, and that this disruption is directly responsible for glucose intolerance—at least in mice. The researchers added three different artificial sweeteners (AS)—saccharin, sucralose and aspartame—to the drinking water of mice. After 10 weeks, all three groups of artificial sweetener-consuming mice showed glucose intolerance. Saccharin showed the most pronounced effect.

As the Duke study had shown that sucralose causes changes in the gut microbiota in mice, the Israeli researchers used antibiotics to wipe out the microbes in the mice that had been made glucose intolerant from consuming artificial sweeteners. Eliminating the microbial community in the mice with antibiotics eliminated their glucose intolerance as well.

The researchers then preformed fecal transplants to make doubly sure that the changing character of the mice gut microbes was behind their changing tolerance of glucose. Poop from mice with AS-caused glucose intolerance was inserted into the colons of mice whose AS-induced glucose intolerance had been removed by treatment with antibiotics. After receiving fecal transplants, the mice’s glucose intolerance returned.

The team then turned its attention to humans, examining dietary data and health metrics from non-diabetic people that had been gathered in in an unrelated, ongoing nutritional study. They found correlations between AS consumption and increased ratio of waist to hip, higher blood glucose, and other metabolic markers associated with pre-diabetics.

What’s tricky about looking at this kind of human data in these cases is that those who are drinking diet sodas might very well be doing so because they are already at risk for obesity or diabetes. In other words, instead of demonstrating that artificial sweeteners make you fat, you might instead be observing that fat people are more likely to use sugar substitutes. So while interesting, this correlation in and of itself could be misleading.

To address this issue the researchers assembled a group of seven healthy volunteers who don’t normally consume artificial sweeteners. For one week, the subjects consumed the maximum FDA allotment of Saccharin. After only one week, four out of the seven volunteers began showing glucose intolerance. Those that did also showed a marked shift in their gut microbial profiles, while the microbial profiles of the subjects that did not show glucose intolerance did not show this change.

The fact that only seven subjects were studied, and for only one week, won’t impress many statisticians. And the authors of the study are quick to point out that their results should not be taken as a call for anyone to change their diet, but rather as a signal that more studies along these lines are warranted. To this end, the National Institute of Health is conducting a large, long-term study on what happens when healthy, non-AS using subjects begin consuming sucralose.

The emerging understanding of the connection between diseases like diabetes and the gut’s microbiota opens up the intriguing possibility of treating disease by manipulating gut microbes. Using antibiotics to wipe out the microbial ecosystem in glucose-intolerant mice is one example of how this might work, but there are other ways as well—and don’t worry, fecal transplants aren’t the only other means. Taking probiotic supplements is another way, but the most important avenue, and easiest, might simply be dietary changes.

Altering one’s diet can be difficult, in part it turns out, because the bacteria in your gut are controlling what you want to eat, according to an article published by the University of California. The paper reviews some recent studies that suggest gut bacteria influence the brain and endocrine system via the vagus nerve, which connects the brain and gut.

“Microbes have the capacity to manipulate behavior and mood through altering the neural signals in the vagus nerve, changing taste receptors, producing toxins to make us feel bad, and releasing chemical rewards to make us feel good,” explained Athena Aktipis, co-founder of the Center for Evolution and Cancer with the Helen Diller Family Comprehensive Cancer Center at UCSF, as quoted in the article.

One example of how gut microbe populations tailor themselves to a particular diet, a bacterium that’s particularly proficient at digesting seaweed is common in the bellies of Japanese people. This begs the question, do Japanese people eat so much seaweed because their microbiome is telling them to, or are seaweed-friendly Japanese microbiomes the result of so much seaweed eating? Probably a bit of both. We can exert control over our microbiomes, but they can control us as well.

As Carlo Maley, director of the UCSF Center for Evolution and Cancer, explained, “There is a diversity of interests represented in the microbiome, some aligned with our own dietary goals, and others not.”

In the coming years, the relationship between diet, gut microbes and health will be further teased apart by scientists, and the role that artificial sweeteners play in this dynamic will surely be more clear. But science moves at a slow, cautious pace. Even if we don’t know exactly how artificial sweeteners can cause us harm, it’s becoming increasingly clear that they do. Consume accordingly.