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That guilt-free treat may not be as innocent as it seems.
A new study suggests that alternative sweeteners commonly found in sugar-free and low-calorie foods and beverages may interfere with the growth of bacteria that help keep the gut healthy.
But the effects aren’t always straightforward. Researchers found more than 100 cases where these ingredients behaved differently when combined with other substances — including one widely used antidepressant.
That could be significant, given the gut microbiome’s far-reaching influence throughout the body.
The complex community of bacteria and other microorganisms living in your intestines plays a key role in digestion, immunity, metabolism and even mental health.
When the makeup of that ecosystem changes, the effects can be wide-reaching. Research has linked an imbalance in the gut microbiome to a higher risk of several chronic conditions, including obesity, heart disease, diabetes, depression and even some cancers.
To investigate how increasingly popular sugar alternatives might affect these microscopic organisms, scientists at the University of Cambridge grew 25 different bacterial species in a lab. The cultures included microbes considered beneficial, neutral or potentially harmful to the gut.
The team then exposed the bacteria to 39 natural and artificial sweeteners and tracked how quickly the organisms multiplied.
They found that about three-quarters of the sweeteners affected the growth of at least one bacterial species. Several slowed down or completely stopped the growth of bacteria linked to a healthy digestive system.
“Sweeteners are often marketed as metabolically neutral, but our study challenges this idea,” Dr. Sonja Blasche, a lead author of the study, said in a press release.
Blasche and her colleagues then took the experiment a step further, pairing the sweeteners with other substances, including caffeine, vanilla extract and eight commonly used drugs.
After all, these sugar alternatives are rarely consumed alone.
“We take them with drinks, in snacks or even in medication to mask bitterness,” Blasche said. “These common combinations could have unintended effects on our gut microbiome.”
The researchers ended up finding more than 100 instances in which a sweetener’s impact on the gut changed when another compound was present.
In 34 cases, the combination became stronger, while in 68 cases, it became weaker.
The biggest surprise involved isosteviol, the sweet compound naturally found in stevia leaves, and duloxetine, an antidepressant commonly sold under the brand name Cymbalta.
When scientists combined the two, they found that the pairing strongly suppressed the growth of Roseburia intestinalis and Parabacteroides merdae.
Both bacteria are considered important members of the gut microbiome and have been linked to digestive health and metabolic regulation.
The finding stands out because duloxetine is widely used for depression, generalized anxiety and chronic pain management. In 2023, more than 4.2 million US patients were prescribed the drug.
The researchers then built a mini version of the gut microbiome in the lab, combining all 25 bacterial species into one community. They tested what happened when that ecosystem was exposed to isosteviol and duloxetine together.
The team found that the combination reduced microbial diversity — a feature often linked to a healthier, more resilient gut. It also reshaped the microbial community, allowing some bacteria to multiply while others declined.
The ripple effects went beyond the microbes themselves. Additional experiments suggested the changes increased toxicity toward certain host cells and disrupted the activity of cells involved in inflammation and immune responses.
“Our study suggests that artificial sweeteners don’t just pass through the body passively — they can interact with gut microbes, and these effects can be amplified or altered by other substances like medications,” said Professor Kiran Patil, the study’s senior author.
Still, the research doesn’t prove that sweeteners or the combinations tested directly cause harm in people.
Instead, it adds to a growing list of questions about how sweeteners may influence the body — especially as researchers continue investigating possible connections between sweetener consumption and conditions such as type 2 diabetes, obesity and cancer.
“These findings can help guide new studies towards understanding how sweeteners might influence health in unexpected ways,” Patil said.
Looking ahead, researchers say the next step is finding out whether these interactions happen in people, what amounts are needed to trigger them and whether changes in gut bacteria actually affect health.
For now, these alternatives aren’t going anywhere.
As Americans search for ways to cut calories and food companies reformulate products to meet changing demands, the use of sweeteners continues to climb.
Today, they’re a fixture of the modern diet, with about 40% of Americans regularly consuming sugar substitutes.
