Scientists tested 39 artificial sweeteners and found that at least one intestinal bacteria was most affected

We all know the problem of eating too much sugar. Therefore, millions of people are looking for alternatives. Whether it’s diet drinks, protein bars, gum, or countless other “sugar-free” foods, sugar substitutes have become a huge industry.

But how much do we actually understand what these alternatives do once they reach the gut? In particular, how they interact with our health Gut bacteria?

In a new laboratory study, scientists tested 39 commercially used sweeteners against 25 types of sweeteners Human gut bacteria. They found that nearly three-quarters affected the growth of at least one bacterial strain. But the biggest surprise came when the researchers mixed the sweeteners with other compounds that people commonly consume: more than 100 new interactions emerged, including one in which the sweetener ingredient and a widely used antidepressant became inactivated together.

Not sugar

Sugar substitutes can come in different forms. They include extremely sweet compounds such as aspartame and sucralose, plant-derived stevia compounds, and sugar alcohols such as erythritol and xylitol. Some can provide sweetness with far fewer calories than sugar, and many are hundreds or even thousands of times sweeter, meaning manufacturers only need small amounts. That’s why it’s so attractive.

But replacing sugar doesn’t automatically make a food healthier.

The World Health Organization advises against relying on non-sugary sweeteners for long-term weight control, saying available evidence does not show lasting benefits for reducing body fat. In addition, there’s another question that researchers are just beginning to solve: What happens when these compounds reach the intestines along with everything else we consume?

This is where the new Cambridge study comes in.

Instead of just looking at individual sweeteners, the researchers tested 39 sweeteners and sugar substitutes against 25 gut bacterial strains, then began combining them with compounds like caffeine, vanillin, and the antidepressant duloxetine. These combinations produced effects that the individual components alone cannot always predict.

The researchers first tested the sweeteners one by one. From 975 pairs of bacteria with sweeteners, they confirmed 30 cases in which the sweetener changed bacterial growth. Isosteviol stood out: it inhibited three bacterial strains while encouraging others.

Then the researchers started putting things together.

They combined the sweeteners with four compounds people might encounter alongside them: caffeine, vanilla flavor, Advantam sweetener, and duloxetine, a commonly prescribed antidepressant. This expanded the experiment to include 3,900 combinations of sweetener compounds and bacteria.

They found 102 significant interactions including nine Bacterial species. Of these, 68 groups weakened each other’s effects. But 34 of them did the opposite: Together, the compounds produced a stronger effect than the researchers expected from either one alone.

One group stood out.

Sweetener and antidepressant compound

Isosteviol, a compound related to the sweetener Stevia, became particularly effective when researchers paired it with the antidepressant duloxetine.

Together, the two blocked forcefully Roseburia intestinalisThese are intestinal bacteria that previous research has linked to glucose regulation and protection against intestinal infections. They were also affected Parabacteroides miradayanother common member of the able-bodied Gut microbiome. The University of Cambridge highlighted this association when announcing the study in July.

Essentially, the sweetener and antidepressant compound, when used together in the laboratory, make it more difficult for some naturally beneficial gut bacteria to grow.

The main idea is not that people should stop using sweeteners or stop taking duloxetine. This was a laboratory study, not a human trial. What it shows is that the compounds we consume together can affect our gut bacteria in ways that are difficult to predict by studying each individually.

The broader message is that our guts are exposed to a mixture of food additives, medications, caffeine, flavorings and sweeteners all at once. The study indicates that these groups deserve more attention. Researchers now need to test whether the same interactions occur in real people, in real doses, and whether they actually affect health.

Journal reference: Sonia Blash et al. Common xenobiotics modulate gut microbial responses to low-calorie sweeteners in vitro. Molecular systems biology2026; Digital ID: 10.1038/s44320-026-00225-6