Researchers tested 39 commonly used sweeteners on 25 different types of gut bacteria in laboratory experiments.
Many sweeteners slowed the growth of at least one beneficial bacterial species, though the effects varied widely.
Scientists say the findings are an early step and more research is needed to determine what they mean for human health.
Low- and no-calorie sweeteners have become a common ingredient in everything from diet sodas to sugar-free snacks. They're often promoted as a way to reduce sugar intake without adding calories, but researchers are still learning how these ingredients interact with the body beyond their effects on blood sugar or weight.
Now, scientists at the University of Cambridge have taken a closer look at how a wide variety of commercially available sweeteners affect the bacteria that naturally live in the human gut. Their findings suggest that some sweeteners can directly influence the growth of certain gut microbes in laboratory settings, challenging the idea that these ingredients are biologically inactive once consumed.
The researchers emphasize that this was a lab-based study, not one involving people, so the results should not be interpreted as evidence that sweeteners are harmful in everyday use.
“Most of what we know about the potential impact of sweeteners on our health comes from animal research or from population studies,” researcher Professor Kiran Patil said in a news release.
“While these studies have indicated involvement of the microbiome in mediating the effect of sweeteners, it’s difficult to know how sweeteners act in the body – is it through direct interactions with our gut bacteria?”
How the researchers studied sweeteners and gut bacteria
For the study, the team examined 39 commercially used sweeteners, including both artificial and naturally derived options. They exposed 25 different species of gut bacteria to each sweetener individually to see whether bacterial growth changed.
The researchers also wanted to better reflect how sweeteners are actually consumed, since they're rarely eaten alone. To do that, they tested sweeteners alongside four other commonly encountered compounds: caffeine, vanillin (a flavoring ingredient), advantame, and the antidepressant duloxetine. They then measured how these combinations affected bacterial growth and interactions.
Overall, the experiments generated thousands of measurements, allowing the researchers to identify patterns in how different sweeteners and combinations influenced individual bacterial species. Because the work was conducted under controlled laboratory conditions, it focused on direct interactions between the compounds and bacteria rather than the more complex environment of the human digestive tract.
What the findings could mean for consumers
The researchers found that roughly three-quarters of the sweeteners affected the growth of at least one bacterial species.
In many cases, the sweeteners slowed the growth of bacteria considered important for maintaining a healthy gut microbiome.
“Sweeteners are often marketed as metabolically neutral, but our study challenges this idea,” researcher Dr. Sonja Blasche said in the news release. “We found that they can directly affect gut bacteria, particularly when mixed with other compounds such as medication and food additives. These common combinations could have unintended effects on our gut microbiome.”
One finding stood out: isosteviol, a compound produced from stevia, had a much stronger effect when paired with duloxetine. Together, the combination significantly reduced the growth of two bacterial species associated with blood sugar regulation and gut health, suggesting that some sweeteners may interact with medications in unexpected ways.
Even so, the researchers caution that these results came from laboratory experiments and do not necessarily predict what happens inside the human body. Many factors — including digestion, diet, and the complexity of the gut microbiome — could influence whether similar effects occur in people. The team says additional human studies will be needed before drawing conclusions or making changes to dietary recommendations.
“Sweeteners are often marketed as metabolically neutral, but our study challenges this idea,” Professor Patil said. “We found that they can directly affect gut bacteria, particularly when mixed with other compounds such as medication and food additives. These common combinations could have unintended effects on our gut microbiome."