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

Suez, Jotham, Cohen, Yotam, Valdés-Mas, Rafael, Mor, Uria, Dori-Bachash, Mally, Federici, Sara, Zmora, Niv, Leshem, Avner, Heinemann, Melina, Linevsky, Raquel, Zur, Maya, Ben-Zeev Brik, Rotem, Bukimer, Aurelie, Eliyahu-Miller, Shimrit, Metz, Alona, Fischbein, Ruthy, Sharov, Olga, Malitsky, Sergey, Itkin, Maxim, Stettner, Noa, Harmelin, Alon, Shapiro, Hagit, Stein-Thoeringer, Christoph K., Segal, Eran, Elinav, Eran·2022·Cell
DOI 10.1016/j.cell.2022.07.016
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Abstract

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 significantly impaired glycemic responses. Importantly, gnotobiotic mice conventionalized with microbiomes from multiple top and bottom responders of each of the four 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.

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  • Emerging evidence in humans shows links between exposure to additives, including non-sugar sweeteners, emulsifiers, colorants, and nitrates/nitrites, and detrimental health outcomes.

    “emerging evidence in humans shows links between exposure to additives, including non-sugar sweeteners, emulsifiers, colorants, and nitrates/nitrites, and detrimental health outcomes.”

    From Ultra-processed food exposure and adverse health outcomes: umbrella review of epidemiological meta-analyses (2024) · cites this paper as [62]

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Metadata

Authors
Suez, J., Cohen, Y., Valdés-Mas, R., Mor, U., Dori-Bachash, M., Federici, S., Zmora, N., Leshem, A., Heinemann, M., Linevsky, R., Zur, M., Ben-Zeev Brik, R., Bukimer, A., Eliyahu-Miller, S., Metz, A., Fischbein, R., Sharov, O., Malitsky, S., Itkin, M., Stettner, N., Harmelin, A., Shapiro, H., Stein-Thoeringer, C. K., Segal, E., & Elinav, E.
Venue
Cell
Publisher
Elsevier BV
Published
2022-09
Volume
185
Issue
18
Pages
3307-3328.e19
ISSN
0092-8674
DOI
10.1016/j.cell.2022.07.016
Cited by
423
References
21
Language
en
Licence

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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