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

Study information

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Reviewed Marked as Reviewed by Svetlana up on 2025-4-4

study design

randomized controlled trial

Citation

PMID PubMed identifier for scientific articles.

35987213

DOI Digital object identifier for electronic documents.

10.1016/j.cell.2022.07.016

URI

https://pubmed.ncbi.nlm.nih.gov/35987213/

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 CK, Segal E, Elinav E

Journal

Cell

Year

2022

Keywords:

artificial sweeteners, hyperglycemia, metabolic syndrome, metabolomics, metagenomics, microbiome, non-nutritive sweeteners

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.

Experiment 1

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Curated date: 2025/03/27

Curator: Shulamite

Revision editor(s): Shulamite

Subjects

Location of subjects

Israel

Host species Species from which microbiome was sampled. Contact us to have more species added.

Mus musculus

Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology

Feces Cow dung,Cow pat,Droppings,Dung,Excrement,Excreta,Faeces,Fecal material,Fecal matter,Fewmet,Frass,Guano,Matières fécales@fr,Merde@fr,Ordure,Partie de la merde@fr,Piece of shit,Porción de mierda@es,Portion of dung,Portion of excrement,Portion of faeces,Portion of fecal material,Portion of fecal matter,Portion of feces,Portion of guano,Portion of scat,Portionem cacas,Scat,Spoor,Spraint,Stool,Teil der fäkalien@de,Feces,feces

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology

Glucose tolerance test Glucose tolerance test,glucose tolerance test

Group 0 name Corresponds to the control (unexposed) group for case-control studies

Top Responder at Day 21

Group 1 name Corresponds to the case (exposed) group for case-control studies

Bottom Responder at Day 21

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group

The mice were recipients of the bottom sucralose responder human donors at 21 days.

Group 0 sample size Number of subjects in the control (unexposed) group

3

Group 1 sample size Number of subjects in the case (exposed) group

3

Lab analysis

Sequencing type

WMS

16S variable region One or more hypervariable region(s) of the bacterial 16S gene

Not specified

Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance

Illumina

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).

log transformation

Statistical test

Mixed-Effects Regression

Significance threshold p-value or FDR threshold used for differential abundance testing (if any)

0.05

MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?

Yes

Matched on Factors on which subjects have been matched on in a case-control study

age

Signature 1

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Curated date: 2025/03/28

Curator: Shulamite

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Source: Table S7

Description: Linear mixed model test results of top and bottom responders bacteria at day 21 mice (Bottom vs. top day 21 bacteria).

Abundance in Group 1: increased abundance in Bottom Responder at Day 21

NCBI	Quality Control	Links
Alistipes sp. 56_sp_Nov_56_25
Bacteroides neonati
Bacteroides sp. N54.MGS-20
Bacteroides sp. UBA7116
Clostridiales bacterium 1_7_47FAA
Clostridiales bacterium VE202-26
Clostridium perfringens
Clostridium sp. DSM 4029
Coprobacillus sp. 8_2_54BFAA
Fusicatenibacter saccharivorans
Intestinimonas butyriciproducens
Phocaeicola paurosaccharolyticus
[Clostridium] leptum
uncultured Anaerotruncus sp.

Revision editor(s): Shulamite

Signature 2

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Curated date: 2025/03/28

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Source: Table S7

Description: Linear mixed model test results of top and bottom responders bacteria at day 21 mice (Bottom vs. top day 21 bacteria).

Abundance in Group 1: decreased abundance in Bottom Responder at Day 21

NCBI	Quality Control	Links
Africanella massiliensis
Alistipes sp. HGB5
Bacteroides cutis
Culturomica massiliensis
Paraprevotella clara CAG:116
Phocaeicola dorei
Phocaeicola sartorii
Alistipes finegoldii

Revision editor(s): Shulamite

Experiment 2

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Curated date: 2025/03/28

Curator: Shulamite

Revision editor(s): Shulamite

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies

Top Responder at Baseline

Group 1 name Corresponds to the case (exposed) group for case-control studies

Bottom Responder at Baseline

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group

The mice were recipients of the bottom sucralose responder human donors at Baseline.

Lab analysis

Statistical Analysis

Signature 1

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Curated date: 2025/03/29

Curator: Shulamite

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Source: Table S7

Description: Linear mixed model test results of top and bottom responders bacteria at baseline mice (Bottom vs. Top Baseline Bacteria)

Abundance in Group 1: increased abundance in Bottom Responder at Baseline

NCBI	Quality Control	Links
Akkermansia sp. UBA7090
Bacteroides clarus
Bacteroides faecichinchillae
Bacteroides fluxus
Bacteroides fragilis
Bacteroides intestinalis CAG:315
Bacteroides togonis
Bacteroides xylanisolvens
Blautia schinkii
Blautia sp. An249
Blautia sp. CAG:237
Blautia sp. CAG:257
Lachnospiraceae bacterium 1_4_56FAA
Parabacteroides massiliensis

Revision editor(s): Shulamite

Signature 2

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Revision editor(s): Shulamite

Source: Table S7

Description: Linear mixed model test results of top and bottom responders bacteria at baseline mice (Bottom vs. Top Baseline Bacteria)

Abundance in Group 1: decreased abundance in Bottom Responder at Baseline

NCBI	Quality Control	Links
Alistipes senegalensis
Bacteroides ovatus
Bacteroides sp. D1
Bacteroides thetaiotaomicron
Butyricimonas virosa
Coprobacter fastidiosus
Hoylesella timonensis
Parabacteroides merdae
Paraprevotella clara CAG:116
Phocaeicola salanitronis
uncultured Flavonifractor sp.

Revision editor(s): Shulamite