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.
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Non-nutritive sweetener consumption induced glucose intolerance in a microbiota-dependent manner in rodents and humans.
“NNS consumption induced glucose intolerance in a microbiota-dependent manner (56).”
From The gut microbiota at the intersection of diet and human health (2018) · cites this paper as [56]
Emulsifiers and artificial sweeteners can promote metabolic syndrome features in mice by modulating the microbiota.
“Emulsifiers and artificial sweeteners have been shown to be involved in the development of metabolic syndrome features through their modulation of the microbiota in mice46,47.”
From Diet–microbiota interactions as moderators of human metabolism (2016) · cites this paper as [47]
In seven people, high-dose artificial sweeteners caused insulin resistance after 7 days.
“In a study in seven people, artificial sweeteners given at high doses resulted in insulin resistance after only 7 days47”
From Diet–microbiota interactions as moderators of human metabolism (2016) · cites this paper as [47]
Chronic non-caloric artificial sweetener consumption in mice impacts gut microbial community structure, increasing Bacteroides and some Clostridiales.
“Chronic NAS consumption in mice was shown to impact gut microbial community structure133, resulting in an increase in abundance of bacteria belonging to the Bacteroides genus and some members of the Clostridiales order.”
From The microbial pharmacists within us: a metagenomic view of xenobiotic metabolism (2016) · cites this paper as [133]
Germ-free mice colonized with gut microorganisms from NAS-treated mice or stool microorganisms exposed to NAS ex vivo develop glucose intolerance.
“germ-free mice colonized with gut microorganisms from NAS-treated mice or stool microorganisms exposed to NAS ex vivo develop glucose intolerance.”
From The microbial pharmacists within us: a metagenomic view of xenobiotic metabolism (2016) · cites this paper as [133]
Consumption of artificial sweeteners in mice and humans leads to deregulation of intestinal microbiota, with altered glycan degradation promoting decreased glucose tolerance, a pre-diabetic condition.
“Consumption of artificial sweeteners in mice and humans has been shown to lead to deregulation of the intestinal microbiota, with altered glycan degradation capacity promoting decreased glucose tolerance, a pre-diabetic condition [58].”
From Antibiotic-Induced Changes in the Intestinal Microbiota and Disease (2016) · cites this paper as [58]
The alteration of gut microbiome composition by noncaloric artificial sweeteners is associated with induction of glucose intolerance in mice.
“Other dietary compounds known to alter the composition of the gut microbiome include noncaloric artificial sweeteners such as saccharin, sucralose, and aspartame (Suez et al., 2015), a feature with functional implications associated with the induction of glucose intolerance in mice (Suez et al., 2014).”
From Gut reactions: Breaking down xenobiotic–microbiome interactions (2019) · cites this paper as Suez et al., 2014
Nonnutritive sweeteners have been linked to detrimental effects on microbial diversity and composition and decreased butyrate concentration, but evidence is inconsistent, with some reports concluding no clear effects or that only some sweeteners impact the microbial profile.
“Although earlier human studies indicated detrimental effects on microbial diversity and composition (99, 100) and a more recent study linked consumption of nonnutritive sweeteners to a “dysbiosis” [an increasingly redundant term in microbiome research (171)] and a decrease in butyrate concentration (172), some reports have concluded that no clear effects of sweeteners on the microbiota can be”
From Diet and the Microbiota–Gut–Brain Axis: Sowing the Seeds of Good Mental Health (2021) · cites this paper as [100]
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BackgroundBeyond gut feelings: how the gut microbiota regulates blood pressure
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BackgroundEndocannabinoids–at the crossroads between the gut microbiota and host metabolism
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“In another study recent study, it has been reported that by altering gut microbiota artificial sweetener induces glucose intolerance (Suez et al., 2014).”
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“Furthermore, Suez et al.109 did not actually measure any parameter of gut microflora composition at any time in animals given commercial formulations of sucralose in drinking water.”
BackgroundMethodInfluentialArtificial sweeteners and cancer risk: Results from the NutriNet-Santé population-based cohort study
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“revealed findings implicating non-caloric artificial sweeteners (saccharin, sucralose, and aspartame) in the modification of gut microbiota (induction of dysbiosis and glucose intolerance in mice and in healthy humans) [57], which in turn might be involved in the development of some cancers [58].”
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BackgroundDietary simple sugars alter microbial ecology in the gut and promote colitis in mice
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“…dietary compounds known to alter the composition of the gut microbiome include noncaloric artificial sweeteners such as saccharin, sucralose, and aspartame (Suez et al., 2015), a feature with functional implications associated with the induction of glucose intolerance in mice (Suez et al., 2014).”
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“145 When saccharin was administered to individuals that normally do not consume NAS, glucose tolerance was affected in a subset of participants who had alterations in their microbiota compo sition after NAS consumption.”
BackgroundInfluentialSweeteners as food additives in the XXI century: A review of what is known, and what is to come
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“We also performed separate studies to investigate the effects of sucralose on metabolic syndrome, given that artificial sugars, and especially saccharin, have been reported to induce glucose intolerance in mice (16).”
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“53 A high fat/high sugar diet is responsible for alterations of the gut microbiota composition and intestinal permeability and promotes low-grade in fl am-mation and metabolic disorders in mice.”
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“Given the fact that transferring the microbiota of HFD-consuming mice to GF mice caused glucose intolerance in 6 days (37) and significant changes in the luminal butyrate concentrations of recipient GF mice at day 7 post-FMT (38), it is interesting to note that the acquired changes in microbiota in…”
Obesity changes the human gut mycobiome
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The nutrition‐gut microbiome‐physiology axis and allergic diseases
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- Authors
- Suez, J., Korem, T., Zeevi, D., Zilberman-Schapira, G., Thaiss, C. A., Maza, O., Israeli, D., Zmora, N., Gilad, S., Weinberger, A., Kuperman, Y., Harmelin, A., Kolodkin-Gal, I., Shapiro, H., Halpern, Z., Segal, E., & Elinav, E.
- Affiliations
- Weizmann Institute of Science (IL)
- Jerusalem Mental Health Center (IL)
- Tel Aviv University (IL)
- Corresponding author
- Segal, Eran
- Elinav, Eran
- ORCID
- Venue
- Nature
- Published
- 2014-09-17
- Volume
- 514
- Issue
- 7521
- Pages
- 181-186
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W1989947363
- Cited by
- 2,067
- References
- 41
- Citations by year
- 2026: 145 · 2025: 182 · 2024: 175 · 2023: 166 · 2022: 218 · 2021: 190 · 2020: 189 · 2019: 182 · 2018: 159 · 2017: 159 · 2016: 153 · 2015: 123 · 2014: 24 · 2012: 1
- FWCI
- 62.77
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Nursing › Nutrition and Dietetics › Biochemical Analysis and Sensing Techniques
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diet, Metabolism, and Disease
- Keywords
- impaired glucose tolerance, gut microbiota, dysbiosis, saccharin, sucralose, aspartame, obesity, fecal microbiota transplantation, germ-free mice, antibiotic therapy, type 2 diabetes, microbial metabolic pathways, food additives
- MeSH terms
- Animals, Anti-Bacterial Agents, Aspartame, Body Weight, Dietary Fats, Feces, Female, Germ-Free Life, Glucose, Humans, Male, Mice, Inbred C57BL, Saccharin, Sucrose, Sweetening Agents, Glucose Intolerance, Metabolic Syndrome, Gastrointestinal Tract, Waist-Hip Ratio, Mice, Diet, High-Fat, Microbiota
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