Non-nutritive sweeteners (NNS) are broadly incorporated into foods, especially those representing a growing share of the beverage market. NNS are viewed as a noncaloric and desirable alternative to sugar-based sweeteners and are thought to contribute to reducing overall caloric intake. While these compounds have been studied extensively and have long been considered inert, new research has presented a different view and raises new questions about the effects of NNS on human physiology. Namely, the influence on glucose responses, the gastrointestinal epithelium, and the gut microbiome. As the gut microbiome is now recognized as a major mediator of human health and perturbations to this community are generally associated with negative health trajectories or overt disease, interactions between NNS and the gut microbiome are of increasing interest to clinicians and researchers. Several NNS compounds are now hypothesized to affect human physiology by modulating the gut microbiome, though the mechanism for this action remains unclear. The purpose of this review is to discuss the history and current knowledge of NNS, their reported utility and effects on host physiology and the gut microbiome, and describes a model for investigating the underlying mechanism behind reported effects of NNS on the gut microbiome.
Objectives The acute and long-term effects of synthetic sugar substitutes have yet to be fully determined. Importantly, their interactions with the gut epithelium are poorly understood. The objective of this study was to examine the impact of two synthetic sugar substitutes on intestinal epithelial cells in terms of 1) cellular toxicity, 2) effects on cell proliferation, and 3) effects on cellular differentiation. Methods Gut epithelial cells (n = 3/group) were challenged for 3 hours with varying concentrations of saccharin and sucralose, to determine cellular toxicity thresholds, as assessed by MTT assay. Three morphologically distinct epithelial cell lines (HT-29, HT-29MTX, and T84) were also challenged (n = 3/group) with the maximum concentrations of these compounds that did not induce toxicity to evaluate cell proliferation over a 96-hour period. RNA was isolated from synthetic sugar substitute-challenged cells and analyzed for epithelial cell differentiation-related gene expression via CDX2 by qRT-PCR, and normalized to B2M, an epithelial cell reference gene. Results Cellular toxicity assays indicated that 10% w/v sweetener was the maximum level tested that avoided evidence of cellular toxicity. When comparing distinct epithelial cell lines, HT-29MTX and T84 displayed significant differences in cell proliferation when exposed to saccharin (HT29-MTX, P < 0.01) and sucralose (T84, P < 0.01), demonstrating increased cell proliferation, relative to unchallenged controls. Finally, CDX2 expression, a marker of cellular differentiation, was significantly increased in the presence of both saccharin (5% w/v) and sucralose (10% w/v) in HT-29 cells, relative to unchallenged controls (P < 0.05). Conclusions These findings demonstrate that exposure to high concentrations of synthetic sugar substitutes alter proliferation and differentiation of gut epithelial cell lines in vitro, in a cell line-dependent manner. Additional research is necessary to determine whether these interactions also occur in vivo. Funding Sources This work was funded by the University of Nevada, Reno Department of Nutrition, the College of Agriculture, Biotechnology, & Natural Resources, the Vice President for Research and Innovation, and the Nevada Agricultural Experiment Station.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.