This study provides evidence of the potential risk of Ace-K consumption based on its metabolism by the human gut microbiome, with dose-dependent effects on gut bacterial composition, butyrate production, and intestinal epithelial barrier integrity.
Key Findings
Results
Acesulfame K caused dose-dependent increases in specific gut bacterial taxa in a dynamic gut simulator using children's gut microbiota.
Taxa showing dose-dependent increases included Anaerostipes, Coprococcus, Subdoligranulum, Blautia, Sutterella wadsworthensis, Alistipes, and Bacteroides thetaiotaomicron.
Effects were evaluated using metataxonomics, metagenomics, and metabolic activity analyses.
The gut microbiota was developed in a dynamic gut simulator modeling children's gut conditions.
Effects were characterized as dose-dependent, implying multiple Ace-K concentrations were tested.
Results
Butyrate production showed a dose-response increase correlated with Ace-K consumption, suggesting microbial metabolism of the sweetener.
Butyrate increase correlated with Ace-K dose, suggesting the sweetener itself serves as a substrate for microbial metabolism.
Species such as Anaerostipes hadrus and Intestinimonas were identified as capable of metabolizing Ace-K degradation products to produce butyrate.
Butyrate production was linked to the butanoyl-CoA pathway.
The proposed degradation pathway involves Ace-K breakdown releasing sulfamate and acetoacetate, which are then metabolized to butyrate.
Results
Gut bacteria showing increased abundance possessed sulfatase and amidase enzymatic activities potentially capable of degrading Ace-K.
Increasing bacterial taxa were found to encode sulfatase and amidase activities based on metagenomic analysis.
These enzymatic activities are proposed to cleave Ace-K, releasing sulfamate and acetoacetate as degradation products.
This represents a mechanistic explanation for how gut bacteria metabolize the sweetener.
Findings were supported by both metagenomic and metabolic activity data.
Results
Ace-K–microbiome interaction led to a dose-dependent decrease in Caco-2 epithelial cell integrity.
Caco-2 cells, a model of intestinal epithelial barrier function, showed reduced integrity in response to Ace-K-microbiome interaction products.
The effect was dose-dependent, increasing with higher Ace-K concentrations.
The decrease in epithelial integrity was attributed possibly to the release of sulfated metabolites produced during Ace-K microbial degradation.
This finding suggests a potential mechanism by which Ace-K consumption could damage the intestinal barrier.
Background
Knowledge about the Ace-K–gut microbiota interaction was previously limited prior to this study.
Acesulfame K is described as a commonly consumed sweetener.
The study was designed to address this gap by evaluating dose-dependent effects on metataxonomics, metagenomics, and metabolic activity.
Children's gut microbiota was specifically used as the model system.
The study represents a comprehensive multi-omics approach to characterizing the Ace-K–microbiome interaction.
Results
The study proposes a complete microbial degradation pathway for Ace-K leading to butyrate production via sulfamate and acetoacetate intermediates.
The proposed pathway involves initial cleavage of Ace-K by bacterial sulfatase and amidase enzymes.
This releases sulfamate and acetoacetate as intermediate metabolites.
Acetoacetate is then metabolized by species including Anaerostipes hadrus and Intestinimonas via the butanoyl-CoA pathway to produce butyrate.
Sulfated metabolites released in this process are proposed as the likely cause of intestinal barrier damage observed in Caco-2 cells.
What This Means
This research suggests that acesulfame K (Ace-K), an artificial sweetener widely used in foods and beverages, is not simply passed through the body unchanged — instead, bacteria living in the human gut can actually break it down. Using a laboratory system that simulates the gut environment of children, researchers found that increasing doses of Ace-K led to growth of specific gut bacteria and increased production of a compound called butyrate, which is normally considered beneficial. The findings point to a specific chain of events: gut bacteria use enzymes called sulfatases and amidases to split Ace-K into smaller pieces, which are then further converted into butyrate by bacteria such as Anaerostipes hadrus and Intestinimonas.
However, the breakdown of Ace-K also appears to release sulfur-containing (sulfated) metabolites that may be harmful to the intestinal lining. When researchers exposed intestinal epithelial cells (Caco-2 cells, a standard laboratory model of the gut lining) to the products of this microbial Ace-K metabolism, they observed dose-dependent reductions in the integrity of the cell layer — meaning the protective barrier of the gut appeared to be damaged more as Ace-K doses increased. This raises questions about whether regular Ace-K consumption could compromise gut barrier function.
This research suggests that the interaction between Ace-K and gut microbiota is more complex than previously understood and may carry potential risks, particularly related to intestinal barrier health. The findings are especially relevant given that Ace-K is commonly consumed by children, whose gut microbiomes were specifically studied here. Further research in living subjects would be needed to confirm these effects, but this study highlights the importance of understanding how artificial sweeteners are processed by the trillions of bacteria that inhabit the human gut.
Bellanco A, Yépez-Notario C, Lozano M, Martínez-Cuesta M, Requena T. (2026). Human Gut Microbiome Can Degrade the Sweetener Acesulfame K with Potential Damaging Effects in the Intestinal Barrier Function.. Journal of agricultural and food chemistry. https://doi.org/10.1021/acs.jafc.5c16498