Suez · Cell 2022 · randomized controlled trial · n=120

Personalized microbiome-driven effects of non-nutritive sweeteners on human glucose tolerance.

Cited 394 times in the scientific literature.

Level 2 - randomized trial

Individual randomized controlled trial

PubMed 35987213 · doi:10.1016/j.cell.2022.07.016 · record verified 2026-08-30

What was done

Researchers conducted a randomized controlled trial in 120 healthy adults who received saccharin, sucralose, aspartame, or stevia sachets for 2 weeks at doses below the acceptable daily intake. These four intervention groups were compared against two control arms: one receiving the vehicle (glucose) and one receiving no supplement. Stool and oral microbiomes, plasma metabolomes, and glycemic responses were measured. Causality and mechanisms were evaluated by transplanting microbiomes from human top and bottom glycemic responders into gnotobiotic mice.

What was found

Each of the four non-nutritive sweeteners distinctly altered the composition of stool and oral microbiomes as well as the plasma metabolome. Saccharin and sucralose significantly impaired glycemic responses in humans, though the abstract reports no numerical effect sizes or confidence intervals. In gnotobiotic mice, fecal transplants reproduced the donor-specific glycemic responses, confirming that the glycemic impairments were microbiome-driven.

Why it matters

This trial demonstrates that non-nutritive sweeteners are not physiologically inert in humans and can drive individualized disruptions in glycemic tolerance via microbiome alterations.

Limits

The abstract provides no exact numerical values, effect sizes, or variance metrics. The intervention lasted only 2 weeks, was restricted to healthy adults, and did not evaluate long-term metabolic outcomes or clinical disease endpoints.

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