Effect of sweeteners and sweetness enhancers on health, obesity and gut microbiota composition - a multicentre, randomised, controlled SWEET project.

The role of sweeteners and sweetness enhancers (S&SEs) in body weight regulation and gut microbiota composition remains debated. Here, we investigate their prolonged effects on weight loss maintenance, gut microbial composition, and secondarily on cardiometabolic health. This 1-year multicentre SWEET randomized controlled trial (RCT) includes 341 adults and 38 children with overweight or obesity. Adults follow a 2-months low-energy diet for 5% weight loss, followed by a 10-months healthy ad libitum diet with <10 energy-% from sugars. One group replaces sugar-rich products with S&SEs products (S&SEs group), while the other does not (Sugar group). We show that the S&SEs group, compared to the Sugar group, maintains greater weight loss at 1-year (1.60.7 kg, P=0.029) and exhibits distinct gut microbiota shifts, with increased short-chain fatty acid (SCFA) and methane (CH4)-producing taxa (q<0.05). No significant differences are observed in cardiometabolic markers (p>0.05) and in children. Our findings indicate beneficial effects of S&SEs in a healthy diet to support weight loss maintenance and distinct gut microbiota shift in adults without affecting metabolic health.