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  • Artificial sweeteners induce glucose intolerance by altering the gut microbiota.

Artificial sweeteners induce glucose intolerance by altering the gut microbiota.

Nature (2014-09-19)
Jotham Suez, Tal Korem, David Zeevi, Gili Zilberman-Schapira, Christoph A Thaiss, Ori Maza, David Israeli, Niv Zmora, Shlomit Gilad, Adina Weinberger, Yael Kuperman, Alon Harmelin, Ilana Kolodkin-Gal, Hagit Shapiro, Zamir Halpern, Eran Segal, Eran Elinav
ABSTRACT

Non-caloric artificial sweeteners (NAS) are among the most widely used food additives worldwide, regularly consumed by lean and obese individuals alike. NAS consumption is considered safe and beneficial owing to their low caloric content, yet supporting scientific data remain sparse and controversial. Here we demonstrate that consumption of commonly used NAS formulations drives the development of glucose intolerance through induction of compositional and functional alterations to the intestinal microbiota. These NAS-mediated deleterious metabolic effects are abrogated by antibiotic treatment, and are fully transferrable to germ-free mice upon faecal transplantation of microbiota configurations from NAS-consuming mice, or of microbiota anaerobically incubated in the presence of NAS. We identify NAS-altered microbial metabolic pathways that are linked to host susceptibility to metabolic disease, and demonstrate similar NAS-induced dysbiosis and glucose intolerance in healthy human subjects. Collectively, our results link NAS consumption, dysbiosis and metabolic abnormalities, thereby calling for a reassessment of massive NAS usage.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Saccharin, ≥99%
Sigma-Aldrich
Sucralose, ≥98.0% (HPLC)
Sigma-Aldrich
D-Glucose-12C6, 16O6, 99.9 atom % 16O, 99.9 atom % 12C
Sigma-Aldrich
D-(+)-Glucose, BioUltra, anhydrous, ≥99.5% (sum of enantiomers, HPLC)
Sigma-Aldrich
Saccharin, ≥98%
Sigma-Aldrich
Sodium propionate, ≥99.0%
Sigma-Aldrich
D-(+)-Glucose, Hybri-Max, powder, BioReagent, suitable for hybridoma
Sigma-Aldrich
D-(+)-Glucose, ≥99.5% (GC)
Sigma-Aldrich
D-(+)-Glucose, suitable for mouse embryo cell culture, ≥99.5% (GC)
Sigma-Aldrich
D-(+)-Glucose, ACS reagent
Sigma-Aldrich
D-(+)-Glucose, powder, BioReagent, suitable for cell culture, suitable for insect cell culture, suitable for plant cell culture, ≥99.5%
Sigma-Aldrich
Metronidazole, BioXtra
Supelco
Saccharin, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
D-(+)-Glucose, tested according to Ph. Eur.
Supelco
Sucralose, analytical standard
Sigma-Aldrich
D-(+)-Glucose, ≥99.5% (GC), BioXtra
Saccharin, European Pharmacopoeia (EP) Reference Standard
Supelco
D-(+)-Glucose, analytical standard
USP
Saccharin, United States Pharmacopeia (USP) Reference Standard
Sigma-Aldrich
D-(+)-Glucose, Vetec, reagent grade, ≥99.5% (HPLC)
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Vancomycin hydrochloride, Ready Made Solution, 100 mg/mL in DMSO
Supelco
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USP
Sucralose, United States Pharmacopeia (USP) Reference Standard
Sucralose, European Pharmacopoeia (EP) Reference Standard
Sigma-Aldrich
Sodium butyrate, ≥98.5% (GC)
Sigma-Aldrich
L-(−)-Glucose, ≥99%
Sigma-Aldrich
Asp-Phe methyl ester, ≥98%
Sigma-Aldrich
Sucrose, ACS reagent
Sigma-Aldrich
D-(+)-Glucose solution, 100 g/L in H2O, sterile-filtered, BioXtra, suitable for cell culture
Supelco
D-(+)-Glucose solution, 1 mg/mL in 0.1% benzoic acid, standard for enzymatic assay kits GAGO20, GAHK20, STA20, analytical standard