“Personalized Microbiome-Driven Effects of Non-Nutritive Sweeteners on Human Glucose Tolerance”, Jotham Suez, Yotam Cohen, Rafael Valdés-Mas, Uria Mor, Mally Dori-Bachash, Sara Federici, Niv Zmora, Avner Leshem, Melina Heinemann, Raquel Linevsky, Maya Zur, Rotem Ben-Zeev Brik, Aurelie Bukimer, Shimrit Eliyahu-Miller, Alona Metz, Ruthy Fischbein, Olga Sharov, Sergey Malitsky, Maxim Itkin, Noa Stettner, Alon Harmelin, Hagit Shapiro, Christoph K. Stein-Thoeringer, Eran Segal, Eran Elinav2022-09 (microbiome, QS)⁠:

• Randomized-controlled trial on the effects of non-nutritive sweeteners in humans

• Sucralose and saccharin supplementation impairs glycemic response in healthy adults

• Personalized effects of non-nutritive sweeteners on microbiome and metabolome

• Impacts on the microbiome are causally linked to elevated glycemic response

[commentary] Non-nutritive sweeteners (NNS) are commonly integrated into human diet and presumed to be inert; however, animal studies suggest that they may impact the microbiome and downstream glycemic responses.

We causally assessed NNS impacts in humans and their microbiomes in a randomized-controlled trial encompassing 120 healthy adults, administered saccharin, sucralose, aspartame, and stevia sachets for 2 weeks in doses lower than the acceptable daily intake, compared with controls receiving sachet-contained vehicle glucose or no supplement.

As groups, each administered NNS distinctly altered stool and oral microbiome and plasma metabolome, whereas saccharin and sucralose statistically-significantly impaired glycemic responses. Importantly, gnotobiotic mice conventionalized with microbiomes from multiple top and bottom responders of each of the 4 NNS-supplemented groups featured glycemic responses largely reflecting those noted in respective human donors, which were preempted by distinct microbial signals, as exemplified by sucralose.

Collectively, human NNS consumption may induce person-specific, microbiome-dependent glycemic alterations, necessitating future assessment of clinical implications.

[Keywords: microbiome, non-nutritive sweeteners, artificial sweeteners, metabolic syndrome, hyperglycemia, metagenomics, metabolomics]