Sucralose Exposure During Pregnancy Elevates Gestational Diabetes Risk via Gut Microbiota-Metabolic Axis in Mice

Sucralose, a widely used nonnutritive artificial sweetener, has gained increasing popularity during pregnancy due to its low-calorie properties. The influence of sucralose on gestational diabetes mellitus (GDM) risk via alterations in gut microbiota composition is not yet well understood. This study sought to explore how gestational sucralose exposure influences GDM development in mice through gut microbiota dysbiosis, impaired intestinal barrier, and metabolic disorders. As an exploratory extension, we also preliminarily assessed early growth in offspring. In our experimental design, pregnant mice were administered sucralose solution to evaluate GDM incidence. Fecal samples were collected for 16S rRNA sequencing and untargeted metabolomic analysis. To establish causality, gut microbiota from sucralose-exposed pregnant mice was transplanted into control pregnant mice to assess subsequent GDM development and alterations in fecal 16S rRNA profiles. Additionally, we monitored postpartum glucose metabolism in sucralose-treated pregnant mice and tracked offspring body weight changes. Our results demonstrated that sucralose exposure significantly increased GDM incidence, accompanied by higher glucose levels and diminished insulin sensitivity. Furthermore, sucralose administration caused significant gut microbiota imbalance. It reduced beneficial taxa like Prevotellaceae UCG-001 and Lachnospiraceae UCG-001 while increasing the proinflammatory taxon Parasutterella. These changes strongly correlated with key fecal metabolites, including 5-aminopentanoic acid. Notably, maternal sucralose consumption during pregnancy also affected offspring body weight. These findings collectively indicate that gestational sucralose exposure elevates GDM risk in mice through the gut microbiota-metabolism axis, providing critical scientific evidence regarding the safety of low-calorie sweeteners in clinical applications during pregnancy.