Intestinal Nutrient Sensing Group & Centre of Research Excellence in Translating Nutritional Science to Good Health, Adelaide Medical School, The University of Adelaide, South Australia
Nutrition, Diabetes & Gut Health Program, Lifelong Health, South Australian Health & Medical Research Institute
Background: Epidemiological studies indicate that a habitual high intake of non-nutritive sweeteners (NNS) increases the risk of developing type 2 diabetes, but the mechanisms are unknown. NNS activate intestinal sweet taste receptors to trigger gut hormone release, increase intestinal glucose absorption and trigger gut dysbiosis in animals. However, it unknown whether NNS exerts these effects in humans, and if so, whether postprandial glycaemia is adversely affected.
Methods: 36 healthy subjects (aged 29 ± 2 years, 16 female) were randomised in double-blind manner to supplementation with NNS capsules (containing 92 mg sucralose + 52 mg acesulfame-K, N=19) or placebo (hydroxypropyl methylcellulose, N=17) taken three times daily over two-weeks. Subjects underwent non-sedated endoscopy incorporating a 30 min intraduodenal glucose infusion (3 kcal/min, including 3g of the glucose analogue 3-O-methyl glucose, 3‑OMG) with biopsy and stool collection, before and after intervention. Glucose absorption (serum 3‑OMG), plasma glucose and gut peptides were measured, and incremental areas under the curve (iAUC, over 120 min) compared by ANCOVA. Microbiome changes were assessed by shotgun sequencing; taxonomic and functional characteristics were determined using MetaPhlAn2 and HUMAnN2 abundance.
Results: NNS supplementation augmented glucose absorption (15% P ≤ 0.05) as well as glycaemic responses to enteral glucose (56% P ≤ 0.001) and reduced release of glucagon-like peptide-1 (GLP-1, 32% P ≤ 0.1). NNS broadly reduced the relative abundance of multiple potentially beneficial bacteria (i.e., Subdoligranulum, Roseburia, Lachnospiracaea, Bifidobacterium). Changes in microbiome composition and function due to NNS correlated with host glycaemic responses, while shifts in Ruminococcus obeum significantly moderated NNS effects on GLP-1 iAUC0-120 (P < 0.001).
Conclusion: Our findings show that two-week NNS supplementation disrupts gut microbiome composition and impairs control of postprandial glycaemia in healthy humans by dysregulating glucose uptake. This highlights the clinical relevance of dietary NNS to overall glycaemic control.