title: Artificial sweeteners induce glucose intolerance by altering the gut microbiota.
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.
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Jotham
authors.initials: J
authors.lastname: Suez
authors.affiliation: 1] Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot 76100, Israel [2].
authors.forename: Tal
authors.initials: T
authors.lastname: Korem
authors.affiliation: 1] Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot 76100, Israel [2].
authors.forename: David
authors.initials: D
authors.lastname: Zeevi
authors.affiliation: 1] Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel [2].
authors.forename: Gili
authors.initials: G
authors.lastname: Zilberman-Schapira
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Christoph A
authors.initials: CA
authors.lastname: Thaiss
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Ori
authors.initials: O
authors.lastname: Maza
authors.affiliation: Day Care Unit and the Laboratory of Imaging and Brain Stimulation, Kfar Shaul hospital, Jerusalem Center for Mental Health, Jerusalem 91060, Israel.
authors.forename: David
authors.initials: D
authors.lastname: Israeli
authors.affiliation: 1] Internal Medicine Department, Tel Aviv Sourasky Medical Center, Tel Aviv 64239, Israel [2] Research Center for Digestive Tract and Liver Diseases, Tel Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel [3] Digestive Center, Tel Aviv Sourasky Medical Center, Tel Aviv 64239, Israel.
authors.forename: Niv
authors.initials: N
authors.lastname: Zmora
authors.affiliation: The Nancy and Stephen Grand Israel National Center for Personalized Medicine (INCPM), Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Shlomit
authors.initials: S
authors.lastname: Gilad
authors.affiliation: Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Adina
authors.initials: A
authors.lastname: Weinberger
authors.affiliation: Department of Veterinary Resources, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Yael
authors.initials: Y
authors.lastname: Kuperman
authors.affiliation: Department of Veterinary Resources, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Alon
authors.initials: A
authors.lastname: Harmelin
authors.affiliation: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Ilana
authors.initials: I
authors.lastname: Kolodkin-Gal
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Hagit
authors.initials: H
authors.lastname: Shapiro
authors.affiliation: 1] Research Center for Digestive Tract and Liver Diseases, Tel Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel [2] Digestive Center, Tel Aviv Sourasky Medical Center, Tel Aviv 64239, Israel.
authors.forename: Zamir
authors.initials: Z
authors.lastname: Halpern
authors.affiliation: Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Eran
authors.initials: E
authors.lastname: Segal
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Eran
authors.initials: E
authors.lastname: Elinav
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001218:Aspartame / Q000009:adverse effects; D001835:Body Weight / Q000187:drug effects; D059305:Diet, High-Fat; D004041:Dietary Fats / Q000494:pharmacology; D005243:Feces / Q000382:microbiology; D005260:Female; D041981:Gastrointestinal Tract / Q000187:drug effects* / Q000382:microbiology*; D005856:Germ-Free Life; D005947:Glucose / Q000378:metabolism; D018149:Glucose Intolerance / Q000139:chemically induced* / Q000378:metabolism / Q000382:microbiology*; D006801:Humans; D008297:Male; D024821:Metabolic Syndrome / Q000139:chemically induced / Q000378:metabolism / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D064307:Microbiota / Q000187:drug effects*; D012439:Saccharin / Q000008:administration & dosage / Q000009:adverse effects; D013395:Sucrose / Q000009:adverse effects / Q000031:analogs & derivatives; D013549:Sweetening Agents / Q000009:adverse effects*; D049629:Waist-Hip Ratio
chemical_list: D000900:Anti-Bacterial Agents; D004041:Dietary Fats; D013549:Sweetening Agents; D013395:Sucrose; C026285:trichlorosucrose; D012439:Saccharin; D005947:Glucose; D001218:Aspartame