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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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In the citing paper
“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]
In the citing paper
“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 the citing paper
“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]
In the citing paper
“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]
In the citing paper
“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]
In the citing paper
“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]
In the citing paper
“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
In the citing paper
“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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“Artificial sweeteners also influence the intestinal microbiota and alter metabolic function indirectly [95].”
BackgroundMethodLow Calorie Sweeteners Differ in Their Physiological Effects in Humans
Hunter, S., Reister, E. J., Cheon, E., & Mattes, R. D. (2019) · Nutrients · doi:10.3390/nu11112717 · Cited by 85
“[137], there were compositional changes between responders and non-responders prior to consuming saccharin for 7 days, which may reflect different lifestyles between responders and non-responders.”
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Sugar reduction in beverages: Current trends and new perspectives from sensory and health viewpoints
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“…9 and titanium dioxide 10 , as well as ingredients added duringfoodprocessingincluding dietaryemulsi fi ers(polysorbate-80 and carboxy-methylcellulose 11 ) and arti fi cial sweeteners 12 alter the gut microbiome, increase intestinal permeability, decrease mucus barrier thickness, and promote colitis.”
Effect of Non-Nutritive Sweeteners on the Gut Microbiota
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“However, only a few studies have investigated the mechanisms by which gut microbiota can metabolize NNS, showing that they can be used as a carbon source by some strains of gut bacteria, leading to changes in their metabolic activity [70,72].”
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“Previous studies have demonstrated the impact of sweeteners on diversity of gut microbiota [15,19,28].”
BackgroundInfluentialIntestinal Alkaline Phosphatase: A Review of This Enzyme Role in the Intestinal Barrier Function
Santos, G. M., Ismael, S., Morais, J., Araújo, J., Faria, A., Calhau, C., & Marques, C. (2022) · Microorganisms · doi:10.3390/microorganisms10040746 · Cited by 73
Modulation of gut‐microbiota through probiotics and dietary interventions to improve host health
Dasriya, V. L., Samtiya, M., Ranveer, S. A., Dhillon, H. S., Devi, N., Sharma, V., Nikam, P., Puniya, M., Chaudhary, P., Chaudhary, V., et al. (2024) · Journal of the Science of Food and Agriculture · doi:10.1002/jsfa.13370 · Cited by 85
Dysbiotic drift: mental health, environmental grey space, and microbiota
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“The increasing use of artificial sweeteners by socioeconomically disadvantaged and minority communities [305] may also promote dysbiosis [306-308].”
BackgroundGuidelines for Transparency on Gut Microbiome Studies in Essential and Experimental Hypertension
Marques, F. Z., Jama, H. A., Tsyganov, K., Gill, P. A., Rhys-Jones, D. R., Muralitharan, R. R., Muir, J. G., Holmes, A. J., & Mackay, C. R. (2019) · Hypertension · doi:10.1161/hypertensionaha.119.13079 · Cited by 80
“senior author(37)), which can lead to microbial changes on its own.(38) Thus, once or twice daily oral gavage of antibiotics”
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Degradation of chondroitin sulfate by the gut microbiota of Chinese individuals
Shang, Q., Yin, Y., Zhu, L., Li, G., Yu, G., & Wang, X. (2016) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2016.01.055 · Cited by 76
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“In addition, the exposure to saccharin, sucralose, and especially aspartame-promoted alterations of the gut microbiota leading to an impaired glucose tolerance (24, 26).”
Andermann, T. M., Rezvani, A. R., & Bhatt, A. S. (2016) · Current Hematologic Malignancy Reports · doi:10.1007/s11899-016-0302-9 · Cited by 78
Sugar-sweetened beverage consumption and genetic predisposition to obesity in 2 Swedish cohorts
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“However, a recent study in humans suggests that the constitution of the gut microbiota might mediate the association between the consumption of artificial sweeteners and glucose intolerance (23).”
BackgroundThe Role of Bacteria, Probiotics and Diet in Irritable Bowel Syndrome
Harper, A. J., Naghibi, M., & Garcha, D. S. (2018) · Foods · doi:10.3390/foods7020013 · Cited by 82
“Saccharin, sucralose, or aspartame were shown to change the composition and function of the gut microbiota and drive glucose intolerance in both animal and human models [129].”
BackgroundNettleton, J. E., Klančič, T., Schick, A., Choo, A. C., Shearer, J., Borgland, S. L., Chleilat, F., Mayengbam, S., & Reimer, R. A. (2019) · Nutrients · doi:10.3390/nu11061248 · Cited by 87
“For example, Suez and colleagues observed glucose intolerance in lean and obese mice and human participants fed saccharin, and fecal microbiota transplant transferred this adverse phenotype to germ-free mice [17].”
BackgroundMicrobiome and Mental Health, Specifically as It Relates to Adolescents
Simkin, D. R. (2019) · Current Psychiatry Reports · doi:10.1007/s11920-019-1075-3 · Cited by 82
Méndez-García, L. A., Bueno-Hernández, N., Cid-Soto, M. A., León, K. L. D., Mendoza-Martínez, V. M., Espinosa-Flores, A. J., Carrero-Aguirre, M., Esquivel‐Velázquez, M., León-Hernández, M., Viurcos-Sanabria, R., et al. (2022) · Microorganisms · doi:10.3390/microorganisms10020434 · Cited by 75
“Similarly, mice drinking sucralose for eleven weeks show glucose intolerance associated with an increased intestinal abundance of bacteria belonging to the phyla Bacteroidetes and Actinobacteria, such as Bacteroides uniformis and Bifidobacterium longum [2].”
BackgroundGut Microbiome: Profound Implications for Diet and Disease
Hills, R. D., Pontefract, B., Mishcon, H. R., Black, C. A., Sutton, S. C., & Theberge, C. R. (2022) · Kompass Nutrition & Dietetics · doi:10.1159/000523712 · Cited by 79
“In humans, the average bacterial-epithelial distance of closest bacteria correlates inversely with BMI, fasting glucose levels, and hemoglobin A1c [271].”
BackgroundInfluentialAntibiotic-perturbed microbiota and the role of probiotics
Szajewska, H., Scott, K. P., de Meij, T. G. J., Forslund, S. K., Knight, R. D., Koren, O., Little, P. S., Johnston, B. C., Łukasik, J., Suez, J., et al. (2024) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-024-01023-x · Cited by 80
“Furthermore, individual drugs (for example, antibiotics and metformin 115 ) or food ingredients (for example, certain artificial sweeteners 116 or emulsifiers 117 ) have been reported to reduce gut microbial diversity, either by epidemiological association in humans or by controlled experiments in…”
Self-citationLi, X., Liu, Y., Wang, Y., Li, X., Liu, X., Guo, M., Tan, Y., Qin, X., Wang, X., & Jiang, M. (2020) · Frontiers in Oncology · doi:10.3389/fonc.2020.00710 · Cited by 76
“Papers published in recent years in Nature showed that food additives such as artificial sweeteners and emulsifiers increased the risk of diabetes, obesity, and colitis through their adverse impact on gut bacteria (20, 21).”
BackgroundEarly Exposure to Nonnutritive Sweeteners and Long-term Metabolic Health: A Systematic Review
Reid, A. E., Chauhan, B. F., Rabbani, R., Lys, J., Copstein, L., Mann, A. S., Abou-Setta, A. M., Fiander, M., MacKay, D., McGavock, J., et al. (2016) · PEDIATRICS · doi:10.1542/peds.2015-3603 · Cited by 76
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“27,30,31,38 Our results differ from previous findings for A. municiphila and suggest that Bacteroides patterns of enrichment or depletion might be species-or strain-specific, warranting further research with deeper resolution.”
BackgroundResultCurrent Innovations in the Development of Functional Gummy Candies
Tarahi, M., Tahmouzi, S., Kianiani, M. R., Ezzati, S., Hedayati, S., & Niakousari, M. (2023) · Foods · doi:10.3390/foods13010076 · Cited by 76
“On the other hand, some studies showed that the consumption of artificial sweeteners (e.g., saccharin, sucralose, aspartame) in food formulations may cause glucose intolerance by inducing compositional and functional changes in the gastrointestinal microbiota [47].”
BackgroundDiet, interleukin-17, and childhood asthma in Puerto Ricans
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“A recent study indicates that noncaloric artificial sweeteners alter microbial metabolic pathways linked to host susceptibility to dysbiosis and glucose intolerance(36); dysregulation of these pathways through diet has been linked to AHR and allergic airway inflammation(7, 37).”
BackgroundApproaches to studying and manipulating the enteric microbiome to improve autism symptoms
Frye, R. E., Slattery, J. M., MacFabe, D. F., Allen‐Vercoe, E., Parker, W., Rodakis, J., Adams, J. B., Krajmalnik‐Brown, R., Bolte, E. R., Kahler, S. G., et al. (2015) · Microbial Ecology in Health and Disease · doi:10.3402/mehd.v26.26878 · Cited by 78
“Other diets empirically attempt to limit refined carbohydrates, foods containing additives, such as the food preservative propionic acid, or artificial sweeteners, which have recently been shown to alter the GM, short-chain fatty acid production, and lipid metabolism (12, 15, 56, 57).”
BackgroundThe growth potential for dairy probiotics
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“This has resulted in multiple studies aimed at manipulating these organisms, through intake of prebiotics, probiotics or specific nutrients, or indeed cessation of products such as artificial sweeteners that induce glucose intolerance (Suez et al., 2014).”
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“(37) demonstrated that artificial sweeteners induced glucose intolerance by altering gut microbiota in mice and that the induced glucose intolerance was abated by treatment with antibiotics.”
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Ecotoxicity and environmental fates of newly recognized contaminants-artificial sweeteners: A review
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“Although, sequencing technologies have been frequently manipulated to understand diet-microbe interactions and its effects on host physiology (Suez et al., 2014) but in CD it needs more advancements.”
BackgroundMeasuring Artificial Sweeteners Toxicity Using a Bioluminescent Bacterial Panel
Harpaz, D., Yeo, L. P., Cecchini, F., Koon, T. H. P., Kushmaro, A., Tok, A. I. Y., Marks, R. S., & Eltzov, E. (2018) · Molecules · doi:10.3390/molecules23102454 · Cited by 72
“To date, diverse methods (e.g., qPCR [63], turbidity [64], selective culturing [65], next-generation sequencing (NGS) [29]) across different species have been used for the determination of potential effects of the artificial sweeteners on microbiome.”
BackgroundMethod
Metadata
- 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
- 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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