Sucralose consumption modifies glucose homeostasis, gut microbiota, Curli protein, and related metabolites in healthy individuals: A randomized placebo-controlled, triple-blind trial.

BACKGROUND & AIMS: Sucralose consumption has been associated with a reduction in insulin sensitivity, potentially through changes in gut microbiota, induction of low-grade inflammation and other pathophysiologic mechanisms, thus the aim of this study was to evaluate the effect of sucralose consumption on glucose tolerance, insulin sensitivity, postprandial glucagon-like peptide 1 (GLP-1), gut microbiota composition, Curli protein, and related metabolites. METHODS: Randomized placebo-controlled triple blind trial including healthy lean individuals assigned to consume 30 % of the sucralose acceptable daily intake or placebo for 30 days. A mixed meal tolerance test (MMTT) was performed before and after intervention to evaluate the postprandial changes in the main outcomes. Insulin sensitivity was estimated with the Matsuda index. Gut microbiota was assessed by sequencing the 16 S rRNA gene. Serum biochemical parameters, branched chain amino acids (BCAA), fatty acid profile, and inflammatory markers were measured. RESULTS: Glucose, insulin and GLP-1 areas under the curve increased after the MMTT, along with a significant decrease in insulin sensitivity after sucralose consumption. A reduction in α-diversity of the gut microbiota was observed. Additionally, proinflammatory markers, BCAA, acetate, and fecal Curli protein increased, whereas serum glutamic acid and fecal butyrate, decreased after sucralose consumption. CONCLUSION: The consumption of sucralose in healthy lean individuals for 30 days caused a 20.3 % significant decrease in insulin sensitivity. This might be mediated by changes in gut microbiota composition associated with related metabolites potentially leading to a pro-inflammatory environment that can affect insulin signaling pathways. CLINICAL TRIAL REGISTRY NUMBER AND WEBSITE WHERE IT WAS OBTAINED: ClinicalTrials.gov Identifier: NCT06094894.