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High-intensity sweetener consumption and gut microbiome content and predicted gene function in a cross-sectional study of adults in the United States
Abstract
Purpose To evaluate gut microbiome in relation to recent high-intensity sweetener consumption in healthy adults.Methods Thirty-one adults completed a four-day food record and provided a fecal sample on the fifth day. Bacterial community in the samples was analyzed using multitag pyrosequencing. Across consumers and nonconsumers of aspartame and acesulfame-K, bacterial abundance was compared using nonparametric statistics, and bacterial diversity was compared using UniFrac analysis. Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) was used to predict mean relative abundance of gene function.Results There were seven aspartame consumers and seven acesulfame-K consumers. Three individuals overlapped groups, consuming both sweeteners. There were no differences in median bacterial abundance (class or order) across consumers and nonconsumers of either sweetener. Overall bacterial diversity was different across nonconsumers and consumers of aspartame (P < .01) and acesulfame-K (P = .03). Mean predicted gene abundance did not differ across consumers and nonconsumers of aspartame or acesulfame-K.Conclusions Bacterial abundance profiles and predicted gene function were not associated with recent dietary high-intensity sweetener consumption. However, bacterial diversity differed across consumers and nonconsumers. Given the increasing consumption of sweeteners and the role that the microbiome may have in chronic disease outcomes, work in further studies is warranted.
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“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”
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“Two cross-sectional studies found an association between NAS intake and a microbiome signature in individuals consuming aspartame and/or AceK (N = 31) [97] or high-consumers of any NAS (N = 381) [20], the latter also associated with impaired metabolic health.”
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Food sweeteners: Angels or clowns for human health?
Hong, Q.-Y., Yan, H., Yang, J., Su, L.-T., Dai, Z.-R., & Zhao, C. (2025) · Current Research in Food Science · doi:10.1016/j.crfs.2025.101032 · Cited by 16
“The results show that the overall bacterial diversity of Ace-K consumers and non-consumers is different (Frankenfeld et al., 2015).”
InfluentialTahmouzi, S., Marand, S. A., Tarahi, M., Almasi, H., Morakian, R., Sadrabad, E. K., & Mollakhalili‐Meybodi, N. (2025) · Comprehensive Reviews in Food Science and Food Safety · doi:10.1111/1541-4337.70208 · Cited by 16
Das, S., Banerjee, P., Jana, S., & Mondal, H. (2025) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2025.1623547 · Cited by 21
Mathur, P., & Bakshi, A. (2023) · Nutrition & Food Science · doi:10.1108/nfs-03-2023-0060 · Cited by 14
Impact of artificial sweeteners and rare sugars on the gut microbiome
Lee, C.-Y., So, Y.-S., Yoo, S., Lee, B., & Seo, D. (2024) · Food Science and Biotechnology · doi:10.1007/s10068-024-01597-x · Cited by 12
“…of the functional composition of the gut microbiota of Ace-K consumers and non-consumers using PICRUSt did not reveal any significant differences between the two groups, suggesting that Ace-K intake was not associated with the functional capacity of the gut microbiota (Frankenfeld et al., 2015).”
Impacts of non-nutritive sweeteners on the human microbiome
Crakes, K. R., Questell, L., Soni, S., & Suez, J. (2025) · Immunometabolism · doi:10.1097/in9.0000000000000060 · Cited by 16
“Sucralose 16S Yes Wu et al [55] United States N = 98 (56”
InfluentialRe‐evaluation of acesulfame K (E 950) as food additive
(FAF), E. P. O. F. A. A. F., Castle, L., Andreassen, M., Aquilina, G., Bastos, M. D. L., Boon, P., Fallico, B., FitzGerald, R., Fernández, M. J. F., Grasl‐Kraupp, B., et al. (2025) · EFSA Journal · doi:10.2903/j.efsa.2025.9317 · Cited by 12
Bueno-Hernández, N., Vázquez-Frías, R., y Abreu, A. T. A., Almeda‐Valdés, P., Barajas-Nava, L. A., Carmona-Sánchez, R., Chávez-Sáenz, J. A., Consuelo‐Sánchez, A., Espinosa-Flores, A. J., Hernández-Rosiles, V., et al. (2019) · Revista de Gastroenterología de México · doi:10.1016/j.rgmx.2019.08.001 · Cited by 11
GIDA KATKI MADDELERİNİN MİKROBİYOTA ÜZERİNE ETKİSİ
Bayram, H. M., & Öztürkcan, A. (2020) · GIDA / THE JOURNAL OF FOOD · doi:10.15237/gida.gd20070 · Cited by 10
Hall, L. N., Sanchez, L. R., Hubbard, J. L., Lee, H., Looby, S. E. D., Srinivasa, S., Zanni, M. V., Stanley, T. L., Lo, J., Grinspoon, S. K., et al. (2017) · Open Forum Infectious Diseases · doi:10.1093/ofid/ofx083 · Cited by 9
“In human studies evaluating the effects of aspartame intake in healthy adults, aspartame consumers demonstrated a difference in overall bacterial diversity, although no differences in bacterial abundance or gene diversity were observed [37].”
BackgroundAn Overview of Current Knowledge of the Gut Microbiota and Low-Calorie Sweeteners
Hughes, R., Davis, C. D., Lobach, A. R., & Holscher, H. D. (2021) · Nutrition Today · doi:10.1097/nt.0000000000000481 · Cited by 9
Diet-Induced Alterations in Gut Microbiota Composition and Function
Rinninella, E., Cintoni, M., Raoul, P. C., Ianiro, G., Laterza, L., Ponziani, F. R., Pulcini, G., Gasbarrini, A., & Mele, M. C. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-819265-8.00035-8 · Cited by 9
Potential Effects of Low-Calorie Sweeteners on Human Health
Chen, H.-P., Kao, Y., Lin, M., Lee, C., Wu, H., & Kuo, H. (2025) · Nutrients · doi:10.3390/nu17172726 · Cited by 7
“AceK is rapidly absorbed and excreted unchanged in urine; however, a human study found no significant differences in gut microbiota between AceK consumers and non-consumers [112].”
Dysregulated microbiota-gut-brain axis
Choudhary, A. K., & Lee, Y. Y. (2017) · Nutrition & Food Science · doi:10.1108/nfs-03-2017-0034 · Cited by 7
Analytical difficulties for determination of acesulfame K in chocolate products
Petrova, S., & Christova-Bagdassarian, V. L. (2020) · Pharmacia · doi:10.3897/pharmacia.67.e55257 · Cited by 7
“A recent study in the United States (Frankenfeld et al. 2015), based on four days of food intake, found that healthy people who did not consume and those who consumed synthetic sweeteners (acesulfame K and aspartame) showed a difference in bacterial diversity.”
BackgroundMechanistic Insights into Aspartame-induced Immune Dysregulation
Choudhary, A. K., & Lee, Y. Y. (2018) · Current Nutrition & Food Science · doi:10.2174/1573401314666181016124250 · Cited by 6
Wei, Y., & Ji, B. (2023) · Eco-Environment & Health · doi:10.1016/j.eehl.2023.05.003 · Cited by 6
“However, some contradictory results have been observed, especially in human studies [14 – 19].”
ResultNon-Nutritive Sweeteners and their Effects on Human Health and the Gut Microbiome
Khan, T. A., Ayoub‐Charette, S., Sievenpiper, J. L., & Comelli, E. M. (2019) · Encyclopedia of Gastroenterology · doi:10.1016/b978-0-12-801238-3.62162-1 · Cited by 6
Potential Health Risks of Artificial Sweeteners
Effenberger, M., & Tilg, H. (2025) · Annual Review of Medicine · doi:10.1146/annurev-med-043024-012626 · Cited by 5
An effect of food additives on microbiome
Kornienko, V. Y., & Minaev, M. Y. (2021) · Theory and practice of meat processing · doi:10.21323/2414-438x-2021-6-3-259-268 · Cited by 5
Zhu, X., Sylvetsky, A. C., McCullough, M. L., Welsh, J. A., Hartman, T. J., Ferranti, E. P., & Um, C. Y. (2025) · Journal of Nutrition · doi:10.1016/j.tjnut.2025.02.022 · Cited by 4
Use of bulk liquid membranes for the removal of aspartame from aqueous media
Diaconu, I., Pârvulescu, O. C., Badea, G. I., Rotaru, M., Orbeci, C., & Cernica, G. (2024) · Journal of Molecular Liquids · doi:10.1016/j.molliq.2024.125456 · Cited by 4
Sweeteners: Sensory properties, digestion, consumption trends, and health effects
Mattes, R. D., Tan, S., & Tucker, R. M. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-821848-8.00014-7 · Cited by 6
The impact of artificial sweeteners on bacterial physiology and the microbiome
Staber, C., Krawiel, D., & McCarthy, R. R. (2026) · Trends in Microbiology · doi:10.1016/j.tim.2026.01.010 · Cited by 3
Bellanco, A., Yépez-Notario, C., Lozano, M., Martínez‐Cuesta, M. C., & Requena, T. (2026) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.5c16498 · Cited by 3
Synthetic sweeteners and their impact on the gut microbiota - current state of knowledge
Wąsik, K., Tomaszuk, S., & Wojtuś, M. (2023) · Journal of Education Health and Sport · doi:10.12775/jehs.2023.13.03.004 · Cited by 4
Visualized sensing of erythritol using a simple enzyme-free catechol-based hydrogel film
Zhang, X., Wu, S. Z., Feng, T., Yan, Y., Wu, S., Chen, Y., Wang, Y., Wang, Q., Hu, N., & Wang, L. (2024) · Analytical Methods · doi:10.1039/d3ay02131a · Cited by 3
The Microbiome, Metabolism, and Networks in Precision Nutrition
Mensah, G. E., Maseng, M. G., Allard, S., & Gilbert, J. A. (2024) · Precision Nutrition · doi:10.1016/b978-0-443-15315-0.00011-0 · Cited by 2
Artificial sweeteners and their impact on human health
Szyca, M., Wawrzeńczyk, M., Jędrzejewska, B., Przeradzki, J., Kotulska, M., Borycka, A., & Lichman, M. (2023) · Medycyna Ogólna i Nauki o Zdrowiu · doi:10.26444/monz/176080 · Cited by 3
“…another study demonstrated that in stool samples collected from healthy adults who consumed aspartame or acesulfame-K for four days, the quantity and relative proportion of major gut microbiota species remained unchanged, but slight alterations were observed in the overall species diversity [25].”
BackgroundYin, X., Shi, Y., Sheng, T., & Ji, C. (2024) · Nutrition Reviews · doi:10.1093/nutrit/nuae140 · Cited by 4
Koester, L. R., Anderson, C. J., Tibbs‐Cortes, B. W., Lyte, M., & Schmitz‐Esser, S. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.05.22.110429 · Cited by 2
Metadata
- Authors
- Frankenfeld, C. L., Sikaroodi, M., Lamb, E., Shoemaker, S., & Gillevet, P. M.
- Affiliations
- George Mason University (US)
- Corresponding author
- Frankenfeld, Cara L.
- Venue
- Annals of Epidemiology
- Publisher
- Elsevier BV
- Published
- 2015-10
- Volume
- 25
- Issue
- 10
- Pages
- 736-742.e4
- ISSN
- 1047-2797 (ISSN-L)
- OpenAlex
- W1823483046
- Cited by
- 123
- References
- 57
- Citations by year
- 2026: 8 · 2025: 11 · 2024: 16 · 2023: 14 · 2022: 10 · 2021: 18 · 2020: 15 · 2019: 10 · 2018: 5 · 2017: 6 · 2016: 8 · 2015: 1
- FWCI
- 2.89
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annals of Epidemiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- George Mason University Microbiome Analysis Center
- 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 › Dentistry › Periodontics › Oral microbiology and periodontitis research
- Keywords
- high-intensity sweeteners, gut microbiota, aspartame, acesulfame-K, bacterial diversity, bacterial abundance, healthy adults
- MeSH terms
- Gastrointestinal Microbiome, Aspartame, Energy Intake, Cross-Sectional Studies, Dietary Carbohydrates, Dose-Response Relationship, Drug, Feces, Female, Humans, Male, Sweetening Agents, Thiazines, United States, Diet Records, Body Mass Index
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