The DOI matches its Crossref record; 65 of the 65 references it cites were found in a registry or an index.
Non-caloric artificial sweeteners and the microbiome: findings and challenges
Open accessAbstract
Non-caloric artificial sweeteners (NAS) are common food supplements consumed by millions worldwide as means of combating weight gain and diabetes, by retaining sweet taste without increasing caloric intake. While they are considered safe, there is increasing controversy regarding their potential ability to promote metabolic derangements in some humans. We recently demonstrated that NAS consumption could induce glucose intolerance in mice and distinct human subsets, by functionally altering the gut microbiome. In this commentary, we discuss these findings in the context of previous and recent works demonstrating the effects of NAS on host health and the microbiome, and the challenges and open questions that need to be addressed in understanding the effects of NAS consumption on human health.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
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., 2015
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
An obesity-associated gut microbiome with increased capacity for energy harvest
Turnbaugh, P. J., Ley, R. E., Mahowald, M. A., Magrini, V., Mardis, E. R., & Gordon, J. I. (2006) · Nature · doi:10.1038/nature05414 · Cited by 12,444
Diet rapidly and reproducibly alters the human gut microbiome
David, L. A., Maurice, C. F., Carmody, R. N., Gootenberg, D. B., Button, J. E., Wolfe, B. E., Ling, A. V., Devlin, A. S., Varma, Y., Fischbach, M. A., et al. (2014) · Nature · doi:10.1038/nature12820 · Cited by 10,100
Human gut microbes associated with obesity
Ley, R. E., Turnbaugh, P. J., Klein, S., & Gordon, J. I. (2006) · Nature · doi:10.1038/4441022a · Cited by 8,785
A metagenome-wide association study of gut microbiota in type 2 diabetes
Qin, J., Li, Y., Cai, Z., Li, S., Zhu, J., Zhang, F., Liang, S., Zhang, W., Guan, Y., Shen, D., et al. (2012) · Nature · doi:10.1038/nature11450 · Cited by 6,762
Intestinal microbiota metabolism of l-carnitine, a nutrient in red meat, promotes atherosclerosis
Koeth, R. A., Wang, Z., Levison, B. S., Buffa, J. A., Org, E., Sheehy, B. T., Britt, E. B., Fu, X., Wu, Y., Li, L., et al. (2013) · Nature Medicine · doi:10.1038/nm.3145 · Cited by 4,386
Gut Microbiota from Twins Discordant for Obesity Modulate Metabolism in Mice
Ridaura, V. K., Faith, J. J., Rey, F. E., Cheng, J., Duncan, A. E., Kau, A. L., Griffin, N. W., Lombard, V., Henrissat, B., Bain, J. R., et al. (2013) · Science · doi:10.1126/science.1241214 · Cited by 3,788
The impact of the gut microbiota on human health: an integrative view
Clemente, J. C., Ursell, L. K., Parfrey, L. W., & Knight, R. (2012) · Cell · doi:10.1016/j.cell.2012.01.035 · Cited by 3,710
Gut microbiota composition correlates with diet and health in the elderly
Claesson, M. J., Jeffery, I. B., Conde, S., Power, S. E., O’Connor, E. M., Cusack, S., Harris, H. M. B., Coakley, M., Lakshminarayanan, B., O’Sullivan, O., et al. (2012) · Nature · doi:10.1038/nature11319 · Cited by 3,314
Gut metagenome in European women with normal, impaired and diabetic glucose control
Karlsson, F. H., Tremaroli, V., Nookaew, I., Bergström, G., Behre, C. J., Fagerberg, B., Nielsen, J., & Bäckhed, F. (2013) · Nature · doi:10.1038/nature12198 · Cited by 3,115
Microbiota and SCFA in lean and overweight healthy subjects
Schwiertz, A., Taras, D., Schäfer, K., Beijer, S., Bos, N. A., Donus, C., & Hardt, P. D. (2010) · Obesity · doi:10.1038/oby.2009.167 · Cited by 2,457
Inflammasome-mediated dysbiosis regulates progression of NAFLD and obesity
Henao-Mejia, J., Elinav, E., Jin, C., Hao, L., Mehal, W. Z., Strowig, T., Thaiss, C. A., Kau, A. L., Eisenbarth, S. C., Jurczak, M. J., et al. (2012) · Nature · doi:10.1038/nature10809 · Cited by 2,435
Self-citationArtificial sweeteners induce glucose intolerance by altering the gut microbiota
Suez, J., Korem, T., Zeevi, D., Zilberman-Schapira, G., Thaiss, C. A., Maza, O., Israeli, D., Zmora, N., Gilad, S., Weinberger, A., et al. (2014) · Nature · doi:10.1038/nature13793 · Cited by 2,067 · cited 2×
“This phenotype seemed to be microbiome-related, as 2 different antibiotics regimens, targeting Gram-positive or Gram-negative bacteria, abrogated the NAS-induced glucose intolerance.(53) To further study the possible NAS effects on the microbiome, we focused on saccharin.”
BackgroundDiet Drives Convergence in Gut Microbiome Functions Across Mammalian Phylogeny and Within Humans
Muegge, B. D., Kuczynski, J., Knights, D., Clemente, J. C., González, A., Fontana, L., Henrissat, B., Knight, R., & Gordon, J. I. (2011) · Science · doi:10.1126/science.1198719 · Cited by 1,988
High-Fat Diet Determines the Composition of the Murine Gut Microbiome Independently of Obesity
Hildebrandt, M. A., Hoffmann, C., Sherrill–Mix, S. A., Keilbaugh, S. A., Hamady, M., Chen, Y., Knight, R., Ahima, R. S., Bushman, F., & Wu, G. D. (2009) · Gastroenterology · doi:10.1053/j.gastro.2009.08.042 · Cited by 1,576
Samuel, B. S., Shaito, A., Motoike, T., Rey, F. E., Backhed, F., Manchester, J. K., Hammer, R. E., Williams, S. C., Crowley, J., Yanagisawa, M., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0808567105 · Cited by 1,564
Gut Microbiota and Metabolic Endotoxemia in Young Obese Mexican Subjects
Radilla-Vázquez, R. B., Parra‐Rojas, I., Martínez-Hernández, N. E., Márquez‐Sandoval, F., Illades‐Aguiar, B., & Castro-Alarcón, N. (2016) · Obesity Facts · doi:10.1159/000442479 · Cited by 1,200
A Trial of Sugar-free or Sugar-Sweetened Beverages and Body Weight in Children
de Ruyter, J. C., Olthof, M. R., Seidell, J. C., & Katan, M. B. (2012) · New England Journal of Medicine · doi:10.1056/nejmoa1203034 · Cited by 814
Raben, A., Vasilaras, T. H., Møller, A. C., & Astrup, A. (2002) · The American Journal of Clinical Nutrition · doi:10.1093/ajcn/76.4.721 · Cited by 667
Ding, M., Bhupathiraju, S. N., Chen, M., van Dam, R. M., & Hu, F. B. (2014) · Diabetes Care · doi:10.2337/dc13-1203 · Cited by 511 · cited 1×
“However, several studies suggested that counterintuitive links may exist between NAS consumption and the same ailments of the metabolic syndrome they are meant to prevent, such as weight gain,(4,5) cardiovascular disease,(6,7) and type II diabetes mellitus.(8,9) Several physiological mechanisms have been suggested for…”
BackgroundFueling the obesity epidemic? Artificially sweetened beverage use and long-term weight gain.
Fowler, S. P., Williams, K., Resendez, R. G., Hunt, K. J., Hazuda, H. P., & Stern, M. P. (2008) · Obesity · doi:10.1038/oby.2008.284 · Cited by 464
Sweet taste receptors in rat small intestine stimulate glucose absorption through apical GLUT2
Mace, O. J., Affleck, J. A., Patel, N., & Kellett, G. L. (2007) · The Journal of Physiology · doi:10.1113/jphysiol.2007.130906 · Cited by 453
Tordoff, M. G., & Alleva, A. (1990) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/51.6.963 · Cited by 444
Artificial sweeteners produce the counterintuitive effect of inducing metabolic derangements
Swithers, S. E. (2013) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2013.05.005 · Cited by 434
Palmnäs, M. S. A., Cowan, T., Bomhof, M. R., Su, J., Reimer, R. A., Vogel, H. J., Hittel, D. S., & Shearer, J. (2014) · PLoS ONE · doi:10.1371/journal.pone.0109841 · Cited by 348
Abou-Donia, M. B., EL-Masry, E. M., Abdel-Rahman, A. A., McLendon, R. E., & Schiffman, S. S. (2008) · Journal of Toxicology and Environmental Health · doi:10.1080/15287390802328630 · Cited by 348
Tate, D. F., Turner-McGrievy, G., Lyons, E., Stevens, J., Erickson, K., Polzien, K., Diamond, M., Wang, X., & Popkin, B. (2012) · The American Journal of Clinical Nutrition · doi:10.3945/ajcn.111.026278 · Cited by 345
Interaction between colonic acetate and propionate in humans
Wolever, T. M. S., Spadafora, P., & Eshuis, H. (1991) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/53.3.681 · Cited by 333
Miller, P. E., & Perez, V. (2014) · The American Journal of Clinical Nutrition · doi:10.3945/ajcn.113.082826 · Cited by 313
Nonnutritive Sweeteners: Current Use and Health Perspectives
Gardner, C. D., Wylie‐Rosett, J., Gidding, S. S., Steffen, L. M., Johnson, R. K., Reader, D., & Lichtenstein, A. H. (2012) · Circulation · doi:10.1161/cir.0b013e31825c42ee · Cited by 308
A role for sweet taste: Calorie predictive relations in energy regulation by rats.
Swithers, S. E., & Davidson, T. L. (2008) · Behavioral Neuroscience · doi:10.1037/0735-7044.122.1.161 · Cited by 294
Sucralose metabolism and pharmacokinetics in man
Roberts, A. S., Renwick, A. G. C., Sims, J., & Snodin, D. J. (2000) · Food and Chemical Toxicology · doi:10.1016/s0278-6915(00)00026-0 · Cited by 266
Fagherazzi, G., Vilier, A., Sartorelli, D. S., Lajous, M., Balkau, B., & Clavel‐Chapelon, F. (2013) · American Journal of Clinical Nutrition · doi:10.3945/ajcn.112.050997 · Cited by 260
Sucralose affects glycemic and hormonal responses to an oral glucose load
Pepino, M. Y., Tiemann, C. D., Patterson, B. W., Wice, B. M., & Klein, S. (2013) · Diabetes Care · doi:10.2337/dc12-2221 · Cited by 253
Nonnutritive Sweeteners: Current Use and Health Perspectives
Gardner, C., Wylie-Rosett, J., Gidding, S. S., Steffen, L. M., Johnson, R. K., Reader, D., Lichtenstein, A. H., & on behalf of the American Heart Association Nutrition Committee of the Council on Nutrition, P. A. A. M. (2012) · Diabetes Care · doi:10.2337/dc12-9002 · Cited by 229
Low-calorie sweetener consumption is increasing in the United States
Sylvetsky, A. C., Welsh, J. A., Brown, R. J., & Vos, M. B. (2012) · American Journal of Clinical Nutrition · doi:10.3945/ajcn.112.034751 · Cited by 224
High-intensity sweeteners and energy balance.
Swithers, S. E., Martin, A. A., & Davidson, T. L. (2010) · Physiology & Behavior · doi:10.1016/j.physbeh.2009.12.021 · Cited by 206
Payne, A. N., Chassard, C., & Lacroix, C. (2012) · Obesity Reviews · doi:10.1111/j.1467-789x.2012.01009.x · Cited by 204
Blackburn, G. L., Kanders, B. S., Lavin, P. T., Keller, S. M., & Whatley, J. (1997) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/65.2.409 · Cited by 202
Association of Sweetened Beverage Intake with Incident Hypertension
Cohen, L., Curhan, G. C., & Forman, J. P. (2012) · Journal of General Internal Medicine · doi:10.1007/s11606-012-2069-6 · Cited by 123
Laska, M. N., Murray, D. M., Lytle, L. A., & Harnack, L. (2011) · Obesity · doi:10.1038/oby.2011.179 · Cited by 119
Daly, K., Darby, A. C., Hall, N., Nau, A., Bravo, D., & Shirazi‐Beechey, S. P. (2014) · British Journal Of Nutrition · doi:10.1017/s0007114513002274 · Cited by 119
Feijó, F. D. M., Ballard, C. R., Foletto, K. C., Batista, B. A. M., Neves, A. M., Ribeiro, M. F. M., & Bertoluci, M. C. (2012) · Appetite · doi:10.1016/j.appet.2012.10.009 · Cited by 115
Swithers, S. E., Laboy, A. F., Clark, K., Cooper, S., & Davidson, T. L. (2012) · Behavioural Brain Research · doi:10.1016/j.bbr.2012.04.024 · Cited by 112
Swithers, S. E., Baker, C. R., & Davidson, T. L. (2009) · Behavioral Neuroscience · doi:10.1037/a0016139 · Cited by 105
The disposition of saccharin in animals and man—A review
RENWICK, A. G. (1985) · Food and Chemical Toxicology · doi:10.1016/0278-6915(85)90136-x · Cited by 93
Saccharin: A toxicological and historical perspective
Arnold, D. L., Krewski, D. R., & Munro, I. C. (1983) · Toxicology · doi:10.1016/0300-483x(83)90021-5 · Cited by 86
The effect of sodium saccharin in the diet on caecal microflora
Anderson, R. L., & Kirkland, J. J. (1980) · Food and Cosmetics Toxicology · doi:10.1016/0015-6264(80)90188-1 · Cited by 77
Mitsutomi, K., Masaki, T., Shimasaki, T., Gotoh, K., Chiba, S., Kakuma, T., & Shibata, H. (2013) · Metabolism · doi:10.1016/j.metabol.2013.09.002 · Cited by 76
The pharmacokinetics and metabolism of sucralose in the dog
Wood, S. G., John, B. A., & Hawkins, D. R. (2000) · Food and Chemical Toxicology · doi:10.1016/s0278-6915(00)00031-4 · Cited by 73
Gender Dimorphism in Aspartame-Induced Impairment of Spatial Cognition and Insulin Sensitivity
Collison, K. S., Makhoul, N. J., Zaidi, M. Z., Saleh, S. M., Andres, B. L., Inglis, A. L., Al‐Rabiah, R. K., & Al-Mohanna, F. A. (2012) · PLoS ONE · doi:10.1371/journal.pone.0031570 · Cited by 65
Aspartame: Physiology and biochemistry
BIRCH, G. G. (1985) · Food Chemistry · doi:10.1016/0308-8146(85)90085-8 · Cited by 65
The pharmacokinetics and metabolism of sucralose in the mouse
John, B. A., Wood, S. G., & Hawkins, D. R. (2000) · Food and Chemical Toxicology · doi:10.1016/s0278-6915(00)00032-6 · Cited by 64
Appleton, K. M., & Blundell, J. E. (2007) · Physiology & Behavior · doi:10.1016/j.physbeh.2007.04.027 · Cited by 57
The metabolism of saccharin in animals
Lethco, E. J., & Wallace, W. C. (1975) · Toxicology · doi:10.1016/0300-483x(75)90030-x · Cited by 45
Pfeffer, M., Ziesenitz, S. C., & Siebert, G. (1985) · Zeitschrift für Ernährungswissenschaft · doi:10.1007/bf02023668 · Cited by 43
The Influence of Sucralose on Bacterial Metabolism
Young, D. A., & Bowen, W. H. (1990) · Journal of Dental Research · doi:10.1177/00220345900690080601 · Cited by 38
Expert Panel report on a study of Splenda in male rats
Brusick, D., Borzelleca, J. F., Gallo, M. A., Williams, G. M., Kille, J. W., Hayes, A. W., Pi-Sunyer, X., Williams, C., & Burks, W. (2009) · Regulatory Toxicology and Pharmacology · doi:10.1016/j.yrtph.2009.06.013 · Cited by 33
Antihyperglycaemic effect of saccharin in diabetic ob/ob mice
Bailey, C. J., Day, C., Knapper, J. M. E., Turner, S. L., & Flatt, P. R. (1997) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0700871 · Cited by 28
Losada, M. E. O., Loughlin, S. M., Rodríguez-Granillo, G. A., Müller, A., Ottaviano, G., Moriondo, M., Cutrìn, J. C., & Milei, J. (2013) · Cardiovascular Diabetology · doi:10.1186/1475-2840-12-57 · Cited by 28
Degradation of Aspartame in Yogurt Related to Microbial Growth
Keller, S. E., NEWBERG, S. S., KRIEGER, T. M., & Shazer, W. H. (1991) · Journal of Food Science · doi:10.1111/j.1365-2621.1991.tb07965.x · Cited by 19
Losada, M. E. O., Cao, G., Loughlin, S. M., Rodríguez-Granillo, G. A., Ottaviano, G., & Milei, J. (2014) · PLoS ONE · doi:10.1371/journal.pone.0089838 · Cited by 17
Aspartame as a source of essential phenylalanine for the growth of oral anaerobes
Wyss, C. (1993) · FEMS Microbiology Letters · doi:10.1111/j.1574-6968.1993.tb06111.x · Cited by 13
Rettig, S., Tenewitz, J. E., Ahearn, G., & Coughlin, C. (2014) · The FASEB Journal · doi:10.1096/fasebj.28.1_supplement.1118.1 · Cited by 11
Association of soda consumption with subclinical cardiac remodeling in the Framingham heart study
Andersson, C., SULLIVAN, L. M., Benjamin, E. J., Aragam, J. R., Jacques, P. F., Cheng, S. C., & Vasan, R. S. (2014) · Metabolism · doi:10.1016/j.metabol.2014.10.009 · Cited by 10
Cowan, T., Palmnäs, M. S. A., Reimer, R. A., Ardell, K., Yang, J. J., Vogel, H. J., & Shearer, J. (2013) · The FASEB Journal · doi:10.1096/fasebj.27.1_supplement.224.7 · Cited by 8
Research works printed but not linked: 6
- Andersson C, 2014, Metabolism
- de Matos Feijjóa F, 2013, Appetite
- David LA, 2014, Nature
- Cowan TE, 2013, FASEB J, 27, 224
- Oldacay M, 2000, Turk Mikrobiyol Cem Derg, 30, 35
- 10.1177/0022034-5900690080601 · DOI
Cited by
Sorted by citations
You are what you eat: Diet, health and the gut microbiota
Zmora, N., Suez, J., & Elinav, E. (2019) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-018-0061-2 · Cited by 1,792
Cuevas-Sierra, A., Ramos-Lopez, O., Riezu-Boj, J. I., Milagro, F. I., & Martinez, J. A. (2019) · Advances in Nutrition · doi:10.1093/advances/nmy078 · Cited by 523
Effects of Sweeteners on the Gut Microbiota: A Review of Experimental Studies and Clinical Trials
Ruiz‐Ojeda, F. J., Plaza‐Díaz, J., Sáez‐Lara, M. J., & Gil, Á. (2018) · Advances in Nutrition · doi:10.1093/advances/nmy037 · Cited by 470
Flandroy, L., Poutahidis, T., Berg, G., Clarke, G. A., Dao, M. C., Decaestecker, E., Furman, E., Haahtela, T., Massart, S., Plovier, H., et al. (2018) · The Science of The Total Environment · doi:10.1016/j.scitotenv.2018.01.288 · Cited by 417
The Influence of the Gut Microbiome on Host Metabolism Through the Regulation of Gut Hormone Release
Martin, A. M., Sun, E. W. L., Rogers, G. B., & Keating, D. J. (2019) · Frontiers in Physiology · doi:10.3389/fphys.2019.00428 · Cited by 402
Metadata
- Authors
- Suez, J., Korem, T., Zilberman-Schapira, G., Segal, E., & Elinav, E.
- Affiliations
- Weizmann Institute of Science (IL)
- Corresponding author
- Segal, Eran
- Elinav, Eran
- Venue
- Gut Microbes
- Publisher
- Informa UK Limited
- Published
- 2015-03-04
- Volume
- 6
- Issue
- 2
- Pages
- 149-155
- ISSN
- 1949-0976 (ISSN-L)
- 1949-0984
- PMC
- PMC4615743
- OpenAlex
- W1499229679
- Cited by
- 217
- References
- 65
- Citations by year
- 2026: 10 · 2025: 20 · 2024: 25 · 2023: 19 · 2022: 19 · 2021: 20 · 2020: 37 · 2019: 23 · 2018: 27 · 2017: 10 · 2016: 7
- FWCI
- 1.88
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Gut Microbes (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Biochemical Analysis and Sensing Techniques
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diet, Metabolism, and Disease
- Keywords
- gut microbiota, impaired glucose tolerance, metabolic disorders, weight gain, diabetes mellitus, host-microbiome interactions, sweetener safety, human health effects
- MeSH terms
- Gastrointestinal Microbiome, Animals, Diet, Humans, Sweetening Agents, Glucose Intolerance, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review