Just because an artificial sweetener has zero or very few calories doesn't mean there are zero (or very few) health consequences to consuming the sachet.

A randomized controlled trial recently found that regular consumption of sucralose (marketed as Splenda) and saccharin (marketed as Sweet'N Low) can alter microbes in the gut and elevate the body's response to sugar.

These non-nutritive sweeteners are presumed to be chemically inert, but that may not actually be true.

The findings of the recent trial, conducted among 120 participants who identified as strict abstainers from artificial sweeteners of any kind, suggest that regularly consuming some zero-calorie sweeteners has potential downsides for your health – at least in the short term.

Compared to control groups who received a placebo, those participants given daily sachets of saccharin and sucralose for two weeks showed distinct physiological changes in the seven days after the experiment.

Namely, the sweeteners altered their gut microbiome in composition and function, and their glucose tolerance was impaired.

"This seemed to suggest that gut microbes in the human body are rather responsive to each of these sweeteners," explains immunologist Eran Elinav from the Weizmann Institute of Science and the German National Cancer Center.

Meanwhile, other artificial sweeteners – like aspartame (marketed Equal) and stevia (often marketed as Truvia) – did not show the same effects on glucose tolerance.

"When we looked at consumers of non-nutritive sweeteners as groups, we found that two of the non-nutritive sweeteners, saccharin, and sucralose, significantly impacted glucose tolerance in healthy adults," Elinav adds.

"Interestingly, changes in the microbes were highly correlated with the alterations noted in people's glycemic responses."

To further test how some artificial sweeteners change the gut microbiome and the body's response to glucose consumption, researchers turned to mice.

First, researchers created a microbiome based on the changes seen in the randomized-controlled trial. Then, they transplanted this microbiome in the form of stool into a group of sterile mice.

The changes to the animals' blood sugar levels closely mirrored what had been seen in humans, suggesting that artificial sweeteners actually can drive changes in the gut, altering what molecules are secreted into the blood. This, in turn, can influence glucose tolerance.

Given the popularity of artificial sweeteners, the findings are worrisome.

In the human trial, researchers gave participants a daily dose of artificial sweetener well below the recommended daily serving laid out by the United States Food and Drug Administration. Yet there was still a noticeable effect.

Research shows diet can change the make-up of gut microbiomes within a matter of days, but we don't yet know what regular consumption of artificial sweeteners over prolonged times might do.

Everyone's microbiome is structured somewhat differently, which means it's unlikely that everyone will have the same response to artificial sweeteners. That said, the fact that our bodies are responding to these products is worth investigating.

While sugar is known to impact weight gain and glucose tolerance, artificial sweeteners are supposed to slip right through the human body without leaving a trace.

Recent research has found that people who drink diet soda sweetened with aspartame are twice as likely to be obese as those who do not.

Part of the problem might be the very taste of sweetness. Saccharin is over 200 times sweeter than sugar, which means when it interacts with sugar receptors or bacteria in the mouth or gut, it could trigger powerful metabolic effects.

The effects, in turn, could impact our brains, our cravings, and the healthy control of our blood sugar levels.

In recent years, artificial sweeteners have even been connected to dementia and cancer.

"We need to raise awareness of the fact that non-nutritive sweeteners are not inert to the human body as we originally believed," says Elinav.

"With that said, the clinical health implications of the changes they may elicit in humans remain unknown and merit future long-term studies."

In trying to produce a zero-calorie substitute for sugar, we might have ripped open a whole new sachet of problems.

The study was published in Cell.