Laboratory research from the University of Cambridge found that several commercially used sweeteners directly affected gut bacteria, with one sweetener showing stronger effects when combined with the antidepressant duloxetine.
Artificial and low-calorie sweeteners commonly used in foods, beverages and medicines may directly alter the growth of important gut bacteria, according to a laboratory study by researchers at the University of Cambridge. The findings suggest that one sweetener, isosteviol, had a particularly strong effect when combined with the antidepressant duloxetine, although researchers stressed that the results do not establish health effects in humans.
The study, published in Molecular Systems Biology, addresses a longstanding gap in understanding how sweeteners interact with the gut microbiome, the community of microorganisms that plays a key role in digestion, metabolism and immune function. The researchers said the findings could help guide future studies on the health effects of sweeteners, particularly when they are consumed alongside medicines and other food additives.
Sweeteners directly affected gut bacteria in laboratory tests
Sweeteners are widely used in soft drinks, desserts, snacks, cereals and other processed foods. They are often promoted as alternatives to sugar, although previous animal and population studies have linked them to conditions including type 2 diabetes, obesity and cancer.
However, few studies have examined whether sweeteners directly interact with gut bacteria.
To investigate this, researchers from the Medical Research Council (MRC) Toxicology Unit at the University of Cambridge grew 25 species of gut bacteria in the laboratory, representing beneficial, neutral and potentially harmful microbes. Each bacterial species was exposed individually to 39 commercially used sweeteners, including both artificial and naturally derived compounds.
The team found that around three-quarters of the sweeteners altered the growth of at least one bacterial species. Some slowed or completely inhibited the growth of bacteria associated with maintaining a healthy gut.
“Most of what we know about the potential impact of sweeteners on our health comes from animal research or from population studies,” said Professor Kiran Patil from the MRC Toxicology Unit. “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?”
Drug combinations changed the effects
The researchers also examined how sweeteners behaved when combined with substances that people commonly consume or take as medicines. These included caffeine, vanillin, advantame and eight widely used drugs.
More than 100 interactions were identified. In 34 cases, the combinations strengthened the effects of sweeteners on gut bacteria, while in 68 cases the effects became weaker.
The most notable finding involved isosteviol, a sweetener widely used in the food and beverage industry, and duloxetine, an antidepressant. Together, they strongly suppressed Roseburia intestinalis and Parabacteroides merdae, two bacterial species that contribute to digestive health.
To better reflect the complexity of the human gut, the researchers then created a synthetic microbial community containing all 25 bacterial species. When exposed to combinations of sweeteners and drugs, the isosteviol-duloxetine combination reduced overall microbial diversity and changed which bacterial species became more or less abundant.
A diverse gut microbiome is generally considered important for maintaining gut health.
Possible implications for immune function
Further laboratory analysis suggested that the isosteviol-duloxetine combination increased toxicity towards certain host cells and interfered with cells involved in inflammation and immune responses.
“Sweeteners are often marketed as metabolically neutral, but our study challenges this idea,” said Dr Sonja Blasche, lead author of the study at the MRC Toxicology Unit. “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.”
Gut bacteria influence digestion, metabolism, immune responses and overall gut health. Changes in the composition or diversity of the microbiome may affect these biological processes, although this study did not evaluate health outcomes in people.
Human studies still needed
The researchers emphasised that all experiments were conducted in laboratory conditions rather than in humans. They said further research is needed before concluding whether the observed changes in gut bacteria translate into measurable health effects.
“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,” Professor Patil said. “These findings can help guide new studies towards understanding how sweeteners might influence health in unexpected ways.”
The researchers said future human studies will be needed to determine whether these laboratory findings have implications for people who regularly consume sweeteners through foods, beverages or medicines.
