Human Gut Microbiome Can Degrade the Sweetener Acesulfame K with Potential Damaging Effects in the Intestinal Barrier Function

Acesulfame K (Ace-K) is a commonly consumed sweetener, although knowledge about the Ace-K-gut microbiota interaction remains limited. This study evaluates dose-dependent effects of Ace-K on metataxonomics, metagenomics, and metabolic activity of children gut microbiota developed in a dynamic gut simulator. An Ace-K-dose dependent increase in <i>Anaerostipes</i>, <i>Coprococcus</i>, <i>Subdoligranulum</i>, <i>Blautia</i>, <i>Sutterella wadsworthensis</i>, <i>Alistipes,</i> and <i>Bacteroides thetaiotaomicron</i> was observed. Butyrate showed a dose-response increase that correlated with Ace-K consumption, suggesting its microbial metabolism. Increasing bacterial taxa showed sulfatase and amidase activities potentially capable of degrading Ace-K, releasing sulfamate and acetoacetate, which species such as <i>Anaerostipes hadrus</i> and <i>Intestinimonas</i> can metabolize to produce butyrate via the butanoyl-CoA pathway. Furthermore, the Ace-K-microbiome interaction led to a dose-dependent decrease in Caco-2 epithelial integrity, possibly due to the release of sulfated metabolites. This study provides evidence of the potential risk of Ace-K consumption based on its metabolism by the human gut microbiome.