Cambridge researchers have shown how commonly used sweeteners slow the growth of certain gut bacteria. One sweetener in particular, isosteviol, when combined with the antidepressant duloxetine, can significantly impair two important gut bacteria involved in regulating blood sugar levels and gut health, and can affect the body’s immune response.
Scientists say more research is needed to understand the actual health effects of this laboratory study. This laboratory study is one of the first to evaluate the direct effects of sweeteners on gut bacteria, particularly when combined with other substances.
Sweeteners are widely used in a variety of foods and beverages, including soft drinks, sweets, desserts, snacks, and cereals. Although marketed as a healthier alternative to sugar, there is growing evidence of links to diseases such as type 2 diabetes, obesity, and cancer.
Despite the widespread use of sweeteners, few studies have investigated the direct interactions between sweeteners and gut bacteria, the vast microbial community that lives in the gastrointestinal tract and plays a key role in maintaining our bodies’ health.
Most of what we know about the potential effects of sweeteners on our health comes from animal or population studies. Although these studies implicate the microbiome in mediating the effects of sweeteners, it is difficult to know how sweeteners act in the body. Is it due to direct interaction with gut bacteria?”
Professor Kiran Patil, Medical Research Council (MRC) Toxicology Unit, University of Cambridge
“The answer is further complicated by the fact that we rarely consume sweeteners on their own. We consume them with drinks, in snacks, or mixed into medicines to mask bitterness,” added the study’s lead author, Dr Sonya Blachet from the MRC Toxicology Unit.
In a study published in molecular systems biologyDr. Blachet and colleagues looked at how low-calorie artificial sweeteners affect the bacteria that live in the gut, and how these effects change when sweeteners are ingested with other common substances such as caffeine, flavorings, and medications.
The researchers cultivated each of 25 types of gut bacteria in the lab, including beneficial, neutral, and potentially harmful bacteria. They then exposed each culture individually to 39 common commercial sweeteners (including both artificial and natural sweeteners) and measured how well the bacteria grew.
About three-quarters of the sweeteners changed the way at least one bacterial species grew. Some sweeteners slow or stop the growth of certain bacteria associated with a healthy gut.
The researchers then tested each sweetener in combination with common compounds such as caffeine, vanillin (vanilla extract), and advantame (artificial sweetener), as well as eight commonly used drugs, to assess whether they affected gut bacteria. They discovered more than 100 interactions in which sweeteners behave differently when combined with other substances. The combination had a stronger effect in 34 patients, and a weaker effect in 68 patients.
Most impressive was the combination of a sweetener called isosteviol, which is widely used in the food and beverage industry, and the antidepressant duloxetine. This combination strongly inhibits Roseburia intestinalis and Parabacteroides meldaetwo gut bacteria that play an important role in maintaining a healthy digestive system. In the United States, more than 4.2 million patients were prescribed duloxetine in 2023.
Because gut bacteria don’t exist alone, but as part of a “community” in the gut, the researchers created a synthetic community that included all 25 types of bacteria. After growing over time, they tested the communities against different sweetener and drug combinations to see which species increased or decreased, and whether overall diversity changed.
By mimicking what can occur in the human gut in this simplistic way, they showed that the combination of isosteviol and duloxetine reduced microbial diversity. A diverse microbiome is thought to be important for gut health. The combination of sweetener and drug also changed which bacterial species grew or decreased.
Further analysis showed that the social effects of the combination of isosteviol and duloxetine increased toxicity to certain host cells and interfered with other cells involved in the body’s inflammatory and immune responses.
Dr. Brachet said, “Sweeteners are often marketed as metabolically neutral, but our study challenges this idea. We found that sweeteners can have a direct impact on gut bacteria, especially when mixed with other compounds such as pharmaceuticals or food additives. These common combinations can have unintended effects on our gut microbiome.”
The researchers stressed that because the experiment was carried out in a laboratory and no human trials have been conducted, further research is needed before concluding that there are direct health effects on humans.
Professor Patil, senior author of the study, added: “Our study suggests that artificial sweeteners do not simply pass through the body passively, but may interact with gut bacteria, and that these effects may be amplified or modified by other substances, such as drugs. These findings will guide new research to understand how sweeteners can affect health in unexpected ways.”
The research was funded by the European Union’s Horizon 2020 program and the UK Medical Research Council.
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Reference magazines:
Brash, S. others. (2026) Common xenobiotics modulate gut bacterial responses to low-calorie sweeteners in vitro. Molecular systems biology. DOI: 10.1038/s44320-026-00225-6. https://link.springer.com/article/10.1038/s44320-026-00225-6
