For many years, the use of artificial (non-nutritive) sweeteners has been widespread across the globe. A source of profit for the food industry, sweeteners have been considered as an essential alternative to the excessive use of sugar — considered harmful on account of its association with cardiometabolic pathologies, cancers and poor dental health. Sweeteners can be consumed directly and are available in a range of options with different sweetening power, but these supposedly inert and calorie-free compounds can also be found in many foodstuffs. The description of the health risks potentially associated with their regular use is the subject of regular controversy, whether for artificial sweeteners (saccharin, sucralose, aspartame) or for natural sweeteners such as steviol glycosides. In a recent issue of Cell, Suez et al. report results of a randomized controlled trial performed in 120 healthy participants, which shows that non-nutritive sweeteners induce perturbations of glucose tolerance in a proportion of healthy individuals, which might be mediated by compositional and functional changes in the gut microbiome.