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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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 [99]
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“In humans, aspartame might not alter the abundance but the diversity of fecal microbiota [15,16].”
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“106 Stevioside, sugar alcohols, aspartame and acesulfame-K 112 were reported to influence gut bacteria 112 and bacterial metabolites.”
BackgroundImpacts of food additives on gut microbiota and host health
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Non-nutritive sweeteners and their impacts on the gut microbiome and host physiology
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Not-so-healthy sugar substitutes?
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NIH Workshop Report: sensory nutrition and disease
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“, (164, 165)], perhaps reshaping it over generations.”
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“(55) found gut microbiome differences between people who use nonnutritive sweeteners and those who do not.”
BackgroundNon-nutritive Sweeteners and Glycaemic Control
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Gut microbiome-based medical methodologies for early-stage disease prevention
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“43 However, several other human studies did not find significant differences in stool microbial composition in subjects consuming aspartame, 50 various other NSS, 47,51,52 or artificially sweetened beverages.”
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Trakman, G., Lin, W. Y., Wilson-O'Brien, A. L., Stanley, A., Hamilton, A. L., Tang, W., Or, L., Ching, J. Y. L., Morrison, M., Yu, J. Q., et al. (2020) · Nutrients · doi:10.3390/nu12030812 · Cited by 19 · see citing works
“These include the thickener Maltodextrin [16,40] (not covered by CODEX), three emulsifiers and/or thickeners (carrageenan [41], carboxymethylcellulouse [11], polysorbate-80 [15]), three artificial sweeteners (aspartame [42], saccharin [43], sucralose [44]), two nanoparticles (the coloring agent titanium dioxide [30,45…”
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Non/Low-Caloric Artificial Sweeteners and Gut Microbiome: From Perturbed Species to Mechanisms
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The complex relationship between metabolic syndrome and sweeteners
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Interactions of Non-Nutritive Artificial Sweeteners with the Microbiome in Metabolic Syndrome
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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?
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“The results show that the overall bacterial diversity of Ace-K consumers and non-consumers is different (Frankenfeld et al., 2015).”
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Impact of artificial sweeteners and rare sugars on the gut microbiome
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“…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 12 · see citing works
“Sucralose 16S Yes Wu et al [55] United States N = 98 (56”
InfluentialRe‐evaluation of acesulfame K (E 950) as food additive
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GIDA KATKI MADDELERİNİN MİKROBİYOTA ÜZERİNE ETKİSİ
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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 · see citing works
Diet-Induced Alterations in Gut Microbiota Composition and Function
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Potential Effects of Low-Calorie Sweeteners on Human Health
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“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
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“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
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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 · see citing works
Potential Health Risks of Artificial Sweeteners
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Synthetic sweeteners and their impact on the gut microbiota - current state of knowledge
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The Microbiome, Metabolism, and Networks in Precision Nutrition
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Artificial sweeteners and their impact on human health
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- 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 · 2012: 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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