We have been using non-caloric artificial sweeteners for more than a century. Today the food industry is using them in ever-greater quantities in 'diet' foodstuffs and they are recommended for weight loss and for individuals with glucose intolerance and type 2 diabetes mellitus. Eran Elinav and colleagues show that consumption of the three most commonly used non-caloric artificial sweeteners — saccharin, sucralose and aspartame — directly induces a propensity for obesity and glucose intolerance in mice. These effects are mediated by changes in the composition and function of the intestinal microbiota; deleterious metabolic effects can be transferred to germ-free mice by faecal transplantation and can be abrogated by antibiotic treatment. The authors demonstrate that artificial sweeteners can induce dysbiosis and glucose intolerance in healthy human subjects, and suggest that it may be necessary to develop new nutritional strategies tailored to the individual and to variations in the gut microbiota.