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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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Ma, X., Tang, L., Deng, J., Liu, Z., Li, X., Wang, P., & Li, Q. (2021) · Journal of Photochemistry and Photobiology A Chemistry · doi:10.1016/j.jphotochem.2021.113482 · Cited by 30
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Romo-Romo, A., Aguilar-Salinas, C. A., Gómez-Díaz, R. A., Brito-Córdova, G. X., Gómez‐Velasco, D., López-Rocha, M. J., & Almeda‐Valdés, P. (2017) · Revista de investigaci�n Cl�nica · doi:10.24875/ric.17002141 · Cited by 30
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Use of Table Sugar and Artificial Sweeteners in Brazil: National Dietary Survey 2008–2009
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Martínez‐Carrillo, B. E., Rosales-Gómez, C., Ramírez‐Durán, N., Reséndiz‐Albor, A. A., Escoto‐Herrera, J. A., Mondragón-Velásquez, T., Valdés‐Ramos, R., & Castillo-Cardiel, J. A. (2019) · International Journal of Food Science · doi:10.1155/2019/9619020 · Cited by 29
“, in 2014 [36], reported that the consumption of saccharin alters the composition of the intestinal microbiota in mice inducing intolerance to glucose.”
BackgroundLi, Y., Liu, M., Liu, H., Wei, X., Su, X.-H., Li, M., & Yuan, J. (2020) · BioMed Research International · doi:10.1155/2020/9067821 · Cited by 32
Jarmakiewicz-Czaja, S., Sokal-Dembowska, A., & Filip, R. (2020) · Nutrients · doi:10.3390/nu12103073 · Cited by 29
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“These shifts in gut microbiota have been linked to the development of obesity-related glucose intolerance which is transferable to germ-free mice through fecal microbiota transplantation (5, 9, 37).”
BackgroundInfluentialToothpaste ingestion—evaluating the problem and ensuring safety: systematic review and meta-analysis
Petrović, B., Kojić, S., Milić, L., Luzio, A., Perić, T., Marković, E., & Stojanović, G. M. (2023) · Frontiers in Public Health · doi:10.3389/fpubh.2023.1279915 · Cited by 29
“Ingesting large amounts of artificial sweeteners can have laxative effects and may cause gastrointestinal discomfort (9); 4.”
BackgroundSchmidt, M. I., Duncan, B. B., de Castilhos, C. D., Wendland, E., Hallal, P. C., Schaan, B. D., Drehmer, M., Forti, A. C. E., Façanha, C. F. S., & Nunes, M. A. (2016) · BMC Pregnancy and Childbirth · doi:10.1186/s12884-016-0851-x · Cited by 35
“Artificial sweeteners, frequently used in Brazil to sweeten coffee and tea, have been recently shown to drive the development of glucose intolerance in rodents through direct compositional and functional alterations in the intestinal microbiota [46].”
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Combined effect of glyphosphate, saccharin and sodium benzoate on rats
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“Findings from many, but not all, animal studies have suggested an adverse association between high levels of ASBs and glucose intolerance, insulin resistance, and obesity (4, 38, 39).”
ResultMundula, T., Russo, E., Curini, L., Giudici, F., Piccioni, A., Franceschi, F., & Amedei, A. (2022) · Current Medicinal Chemistry · doi:10.2174/0929867329666220430131018 · Cited by 29
Understanding interactions among diet, host and gut microbiota for personalized nutrition
Li, C. (2022) · Life Sciences · doi:10.1016/j.lfs.2022.121265 · Cited by 32
Haldar, S., Jadhav, S. R., Gulati, V., Beale, D. J., Balkrishna, A., Varshney, A., Palombo, E. A., Karpe, A. V., & Shah, R. (2023) · FEMS Microbiology Ecology · doi:10.1093/femsec/fiad103 · Cited by 32
“This is most obvious in the case of antibiotics (Cho et al. 2012 ), but it has also been observed for non-caloric artificial sweeteners (Suez et al. 2014 ) and dietary emulsifiers (Chassaing et al. 2015 ), though the mechanisms by which the latter two influence the microbiota is unknown.”
Fine-tuning of the mucosal barrier and metabolic systems using the diet-microbial metabolite axis
Nagai, M., Obata, Y., Takahashi, D., & Hase, K. (2016) · International Immunopharmacology · doi:10.1016/j.intimp.2016.04.001 · Cited by 28
Impact of Ethanol and Saccharin on Fecal Microbiome in Pregnant and Non-Pregnant Mice
Labrecque, M. T., Malone, D., & Allan, C. A. M. (2015) · Journal of Pregnancy and Child Health · doi:10.4172/2376-127x.1000193 · Cited by 28
“[10] found that Impact of Ethanol and Saccharin on Fecal Microbiome in Pregnant and Non-Pregnant Mice”
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“attributed to the alterations of microbiota in the digestive system [59]; however, the reduction of sweet taste receptor expression in the feeding center may contribute to these problems.”
BackgroundToward a Biopsychosocial Ecology of the Human Microbiome, Brain-Gut Axis, and Health
Maier, K. J., & Al’Absi, M. (2017) · Psychosomatic Medicine · doi:10.1097/psy.0000000000000515 · Cited by 27
“Finally, other than agriculture, the global proliferation of noncaloric artificial sweeteners as the most widely used food additive may functionally modify the gut microbiota and increase susceptibility to metabolic disease consistent with mechanisms of glucose intolerance in humans (98).”
BackgroundAssociations Between Nonnutritive Sweetener Intake and Metabolic Syndrome in Adults
Hess, E. L., Myers, E. A., Swithers, S. E., & Hedrick, V. E. (2018) · Journal of the American College of Nutrition · doi:10.1080/07315724.2018.1440658 · Cited by 28
Learning and memory deficits produced by aspartame are heritable via the paternal lineage
Jones, S. K., McCarthy, D. M., Stanwood, G. D., Schatschneider, C. W., & Bhide, P. G. (2023) · Scientific Reports · doi:10.1038/s41598-023-41213-2 · Cited by 30
“Alternative mechanisms such as changes in oxidative stress and gut microbiome have been proposed as well 26,35,100–104 .”
BackgroundSievenpiper, J. L., Purkayastha, S., Grotz, V. L., Mora, M. R., Zhou, J., Hennings, K., Goody, C. M., & Germana, K. (2025) · Nutrients · doi:10.3390/nu17050793 · Cited by 27
Misra, A., Kumar, A., Kuchay, M. S., Ghosh, A., Gulati, S., Choudhary, N. S., Dutta, D., Sharma, P., Vikram, N. K., Rastogi, A., et al. (2025) · Diabetes & Metabolic Syndrome Clinical Research & Reviews · doi:10.1016/j.dsx.2025.103209 · Cited by 27
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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