BackgroundRecent studies suggest that some nonnutritive sweeteners (NNS) have deleterious effects on the human gut microbiome (HGM). The effect of steviol glycosides on the HGM has not been well studied. ObjectiveWe aimed to evaluate the effects of stevia- compared with sucrose-sweetened beverages on the HGM and fecal short-chain fatty acid (SCFA) profiles. MethodsUsing a randomized, double-blinded, parallel-design study, n = 59 healthy adults [female/male, n = 36/23, aged 31±9 y, body mass index (BMI): 22.6±1.7 kg/m2] consumed 16 oz of a beverage containing either 25% of the acceptable daily intake (ADI) of stevia or 30 g of sucrose daily for 4 weeks followed by a 4-week washout. At weeks 0 (baseline), 4, and 8, the HGM was characterized via shotgun sequencing, fecal SCFA concentrations were measured using ultra-high performance liquid chromatography-tandem mass spectrometry and anthropometric measurements, fasting serum glucose, insulin and lipids, blood pressure, pulse, and 3-d diet records were obtained. ResultsThere were no significant differences in the HGM or fecal SCFA between the stevia and sucrose groups at baseline (P > 0.05). At week 4 (after intervention), there were no significant differences in the HGM at the phylum, family, genus, or species level between the stevia and sucrose groups and no significant differences in fecal SCFA. At week 4, BMI had increased by 0.3 kg/m2 (P = 0.013) in sucrose compared with stevia, but all other anthropometric and cardiometabolic measures and food intake did not differ significantly (P > 0.05). At week 8 (after washout), there were no significant differences in the HGM, fecal SFCA, or any anthropometric or cardiometabolic measure between the stevia and sucrose groups (P > 0.05). ConclusionsDaily consumption of a beverage sweetened with 25% of the ADI of stevia for 4 weeks had no significant effects on the HGM, fecal SCFA, or fasting cardiometabolic measures, compared with daily consumption of a beverage sweetened with 30 g of sucrose. Trial registrationclinicaltrials.gov as NCT05264636
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