It is not known whether consuming sugar substitutes while taking antibiotics changes gut health. The human studies available examine sweeteners and the gut microbiome generally; they do not answer what happens when people use sweeteners during a prescribed antibiotic course. There is no evidence-based reason from these studies to switch sweeteners, stop one, or add a probiotic. If you have a concern about your antibiotic or diet, ask your prescriber or pharmacist.
What the evidence can—and cannot—tell us
Sweeteners and antibiotics have each been studied in relation to gut bacteria, but the specific combination has not been tested in the human evidence identified here. That means the effect of using a sweetener during antibiotic treatment is unresolved—not that an effect has been ruled out.
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Findings from laboratory or animal experiments cannot establish what a person should eat while taking a prescribed antibiotic. Nor does a study of diet during antibiotic treatment establish that sugar substitutes have the same effect as sugar.
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“Sugar substitute” covers different ingredients
Non-sugar sweeteners (NSS) include substances such as aspartame, sucralose, saccharin, acesulfame K, stevia and stevia derivatives. WHO distinguishes these from sugar alcohols, also called polyols, which are sugar derivatives containing calories and are outside the scope of its NSS recommendation. A product labeled a sugar substitute may also combine several ingredients, so findings about a single, pure ingredient cannot automatically be applied to a retail blend.
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What human studies have found
A small trial of aspartame and sucralose
A 2020 randomized, double-blinded crossover trial from a University of Manitoba research team enrolled 17 healthy adults aged 18–45 with a BMI of 20–25. Participants received pure aspartame or sucralose during separate 14-day periods, with a four-week washout between them. The tested daily amounts were 0.425 g of aspartame (14% of the acceptable daily intake) and 0.136 g of sucralose (20% of the acceptable daily intake). The trial was small and short, involved healthy volunteers rather than people taking antibiotics, and therefore does not answer whether either sweetener affects gut health during antibiotic treatment.
A review found mixed results
A 2023 review of human clinical trials and cross-sectional studies reported significant changes in microbiota composition in two of the five clinical trials of non-nutritive sweeteners it examined. The authors also noted limitations in the available polyol trials and called for larger studies, longer interventions, realistic doses and attention to participants’ baseline microbiota. These findings do not support a blanket claim that all sugar substitutes either harm or improve the gut.
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Why experimental findings do not answer the treatment question
A 2014 Nature paper reported microbiome-mediated effects on glucose tolerance in experimental work and a limited human component. Its antibiotic-related finding concerned experimental abrogation of sweetener-associated effects by antibiotic treatment. That is different from studying whether people should consume or avoid sweeteners while taking prescribed antibiotics.
A 2026 Nature report examined sugar-rich foods in patients undergoing allogeneic hematopoietic cell transplantation who received broad-spectrum antibiotics. It concerns a different dietary exposure and a specific transplant setting, so it cannot establish that sugar substitutes have the same effects.
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Does WHO’s sweetener guidance apply to antibiotics?
No. WHO’s 2023 conditional recommendation against using non-sugar sweeteners for weight control and prevention of diet-related disease is not guidance about antibiotic treatment or gut health. WHO says the recommendation is not based on toxicological assessments of individual sweeteners and does not replace safe-intake guidance from JECFA or other authoritative bodies. WHO’s accompanying statement says the recommendation applies generally, with an exception for people with pre-existing diabetes, and does not address diabetes management.
WHO Director for Nutrition and Food Safety Francesco Branca said: “People need to consider other ways to reduce free sugars intake, such as consuming food with naturally occurring sugars, like fruit, or unsweetened food and beverages.” That statement concerns long-term weight control, not what to eat during an antibiotic course.
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Can I use artificial sweetener while taking antibiotics?
The evidence discussed here does not establish that you need to stop or change a sweetener during treatment, or that any particular sweetener is a better choice for your gut. It also does not establish that a sweetener protects the gut. If you are unsure about a specific antibiotic, dietary restriction or health condition, check with your prescriber or pharmacist rather than changing treatment or adding a supplement based on these studies.
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