The sweetener packet you pour into your morning coffee never travels alone. It arrives with caffeine, flavor compounds, and sometimes medication. According to recent research, those companions can change what the sweetener does to your gut.
Sugar has long been blamed for weight gain and illness. Artificial sweeteners, which provide sweetness with few or no calories, were meant to sidestep that problem and were long thought to pass through the body with little effect. Recent research has questioned that assumption.
“Based on the evidence, it may be more helpful to view [artificial] sweeteners as biologically active compounds, not as inert additives that are automatically safer than sugar,” Sonja Blasche, the study’s lead author and a senior research associate at the MRC Toxicology Unit at the University of Cambridge, told The Epoch Times.
Overall, 26 of the 39 sweeteners changed the growth of at least one bacterial species. Isosteviol, a compound derived from stevia, affected four bacterial species, more than any other sweetener tested. Sugar wasn’t a clean bill of health: sucrose and fructose each suppressed one strain, the same number as aspartame, xylitol, and erythritol. Lactose and sucralose had no confirmed effects under the study’s criteria.
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How Common Sweeteners Compared
Direct effects of common sweeteners on 25 gut bacterial strains tested in the lab:
Isosteviol affected more strains than any other sweetener, suppressing three and boosting one. But it is different from steviol glycosides—the sweet-tasting compounds extracted from stevia leaves and used to sweeten foods. Isosteviol can form when steviol glycosides break down under certain processing conditions, but how much people are typically exposed to through food is unclear.
C. symbiosum and L. saccharolytica were especially sensitive, with growth slowed by most of the sweeteners that had any effect. C. symbiosum is considered a commensal bacterium (normal gut resident) but has also been linked to colorectal cancer and inflammatory bowel disease under specific conditions. C. saccharolyticum, now called L. saccharolytica, ferments carbohydrates and can accumulate certain drugs. Still, little is known about the role or abundance of either species in a healthy human gut, Blasche said.
When Sweeteners Meet Other Compounds
People rarely consume sweeteners in isolation, so the researchers also tested what happens when sweeteners are combined with things people typically eat alongside them. They paired each sweetener with another low-calorie sweetener (advantame), caffeine, vanillin (a common flavoring), and duloxetine (antidepressant).
Across 3,900 combinations of sweeteners, compounds, and bacteria, they found 102 significant interactions. Some combinations made the sweetener’s effect on gut bacteria stronger, while others weakened or canceled it out.
For example, vanillin and saccharin had a weaker combined effect than expected, suggesting they partly canceled each other out. Caffeine and advantame also altered some sweeteners’ effects, although no particular pairing stood out.
Duloxetine stood out, significantly slowing the growth of seven of the 25 bacterial strains—more than any individual sweetener. By comparison, isosteviol, the most potent sweetener tested, slowed the growth of three.
One pairing in particular stood out. Together, isosteviol (a stevia-derived compound) and duloxetine (antidepressant) strongly inhibited Roseburia intestinalis and Parabacteroides merdae, two gut bacteria generally associated with a healthy gut. Together, the compounds had a stronger effect than either alone. In Roseburia intestinalis, isosteviol amplified the already substantial effect of duloxetine.
The isosteviol-duloxetine interaction was particularly striking, Blasche said, because “isosteviol alone had essentially no effect on Roseburia intestinalis, the species in which this interaction was identified.”
The finding is notable because certain compounds associated with stevia and antidepressants are already known to affect gut bacteria on their own, said Jotham Suez, assistant professor of molecular microbiology and immunology at the Johns Hopkins Bloomberg School of Public Health, who was not involved in the study.
“It is well established that compounds in stevia can interact with gut bacteria, and that antidepressants are among the pharmaceuticals with the most pronounced effects on the gut microbiome,” Suez told The Epoch Times.
Seeing the two amplify each other, is worth further study, he said, especially because it’s still unclear whether the same thing happens inside the human gut.
From Bacteria to Human Cells
After testing the sweeteners and additives with each of the bacterial strains, researchers then put all 25 gut bacterial species together to see how isosteviol and duloxetine, separately and together, affected the bacterial community.
Together, isosteviol and duloxetine reduced both Roseburia intestinalis and Parabacteroides merdae, lowered microbial diversity, and changed which bacterial species were most abundant.
They then exposed laboratory-grown human cells to the liquid left behind by the treated bacteria. The liquid was more toxic to HeLa cells, a cervical cancer cell line commonly used in laboratory research, suggesting the bacterial byproducts had changed. It also altered how Caco-2 cells, a lab model of the intestinal lining, secreted the immune signaling molecules IL-6 and IL-8, suggesting the changes could affect inflammatory signaling in the gut.
Not a One-Size-Fits-All Risk
The results came from individual bacteria grown in the lab and “may or may not translate to species abundance in microbial communities or the human gut,” Blasche said. The study did not establish whether the changes would be large or lasting enough to affect health, and none of it means every sweetener, or even this combination, poses a risk to everyone.
Approved sweeteners are considered safe within their intake limits, but newer research suggests effects differ by person, particularly for glucose response, appetite regulation, and the microbiome, Kara Siedman, a registered dietitian and vice president of science and partnerships at Resbiotic, a company that sells pre-, pro-, and post-biotic supplements, told The Epoch Times.
“It’s less about finding the ‘perfect’ sweetener and more about supporting a diverse microbiome and a diet built around minimally processed foods.”
