Measuring Artificial Sweeteners Toxicity Using a Bioluminescent Bacterial Panel.

Dorin Harpaz, Loo Pin Yeo, Francesca Cecchini, Trish H P Koon, Ariel Kushmaro, Alfred I Y Tok, Robert S Marks, Evgeni Eltzov

Journal: Molecules (Basel, Switzerland) 2018;23(10):2454

PMID: 30257473

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Plain Language Summary

The use of artificial sweeteners is a highly controversial topic for both human health and environmental pollution. The purpose of this study was to determine the relative toxicity of six artificial sweeteners that have been approved by both FDA and EU on E. coli as a representation of gut bacteria using a bioluminescent bacterial panel. The bioluminescent bacteria were exposed to various concentrations of artificial sweeteners and toxicity patterns were observed. This study found that different artificial sweeteners evoke specific responses on E coli, and this is speculated to be the case for the gut microbiome, potentially impacting human health. The authors also found that this method of using bacterial responses confirmed previous toxicity studies, highlighting it as a viable and affordable toxicity evaluation tool.

Abstract

Artificial sweeteners have become increasingly controversial due to their questionable influence on consumers' health. They are introduced in most foods and many consume this added ingredient without their knowledge. Currently, there is still no consensus regarding the health consequences of artificial sweeteners intake as they have not been fully investigated. Consumption of artificial sweeteners has been linked with adverse effects such as cancer, weight gain, metabolic disorders, type-2 diabetes and alteration of gut microbiota activity. Moreover, artificial sweeteners have been identified as emerging environmental pollutants, and can be found in receiving waters, i.e., surface waters, groundwater aquifers and drinking waters. In this study, the relative toxicity of six FDA-approved artificial sweeteners (aspartame, sucralose, saccharine, neotame, advantame and acesulfame potassium-k (ace-k)) and that of ten sport supplements containing these artificial sweeteners, were tested using genetically modified bioluminescent bacteria from . The bioluminescent bacteria, which luminesce when they detect toxicants, act as a sensing model representative of the complex microbial system. Both induced luminescent signals and bacterial growth were measured. Toxic effects were found when the bacteria were exposed to certain concentrations of the artificial sweeteners. In the bioluminescence activity assay, two toxicity response patterns were observed, namely, the induction and inhibition of the bioluminescent signal. An inhibition response pattern may be observed in the response of sucralose in all the tested strains: TV1061 (MLIC = 1 mg/mL), DPD2544 (MLIC = 50 mg/mL) and DPD2794 (MLIC = 100 mg/mL). It is also observed in neotame in the DPD2544 (MLIC = 2 mg/mL) strain. On the other hand, the induction response pattern may be observed in its response in saccharin in TV1061 (MLIndC = 5 mg/mL) and DPD2794 (MLIndC = 5 mg/mL) strains, aspartame in DPD2794 (MLIndC = 4 mg/mL) strain, and ace-k in DPD2794 (MLIndC = 10 mg/mL) strain. The results of this study may help in understanding the relative toxicity of artificial sweeteners on , a sensing model representative of the gut bacteria. Furthermore, the tested bioluminescent bacterial panel can potentially be used for detecting artificial sweeteners in the environment, using a specific mode-of-action pattern.

Address: School of Material Science and Engineering, Nanyang Technology University, 50 Nanyang Avenue, Singapore 639798, Singapore. [email protected].; Avram and Stella Goldstein-Goren, Department of Biotechnology Engineering, Faculty of Engineering Sciences, Ben Gurion University of the Negev, Beer-Sheva 84105, Israel. [email protected].; Institute for Sports Research (ISR), Nanyang Technology University and Loughborough University, Nanyang Avenue, Singapore 639798, Singapore. [email protected].; School of Material Science and Engineering, Nanyang Technology University, 50 Nanyang Avenue, Singapore 639798, Singapore. [email protected].; TURVAL Laboratories, Ltd. (Laboratori Turval Italia Srl), via J. Linussio 51, 33100 Udine, Italy. [email protected].; Department of Obstetrics and Gynaecology, KK Women's and Children's Hospital, 100 Bukit Timah Road, Singapore 229899, Singapore. [email protected].; School of Science and Technology, Singapore University of Social Sciences, 463 Clementi Road, Singapore 599494, Singapore. [email protected].; Avram and Stella Goldstein-Goren, Department of Biotechnology Engineering, Faculty of Engineering Sciences, Ben Gurion University of the Negev, Beer-Sheva 84105, Israel. [email protected].; The National Institute for Biotechnology in the Negev, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel. [email protected].; The Ilse Katz Centre for Meso and Nanoscale Science and Technology, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel. [email protected].; School of Material Science and Engineering, Nanyang Technology University, 50 Nanyang Avenue, Singapore 639798, Singapore. [email protected].; Institute for Sports Research (ISR), Nanyang Technology University and Loughborough University, Nanyang Avenue, Singapore 639798, Singapore. [email protected].; Avram and Stella Goldstein-Goren, Department of Biotechnology Engineering, Faculty of Engineering Sciences, Ben Gurion University of the Negev, Beer-Sheva 84105, Israel. [email protected].; The National Institute for Biotechnology in the Negev, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel. [email protected].; The Ilse Katz Centre for Meso and Nanoscale Science and Technology, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel. [email protected].; Agriculture Research Organization (ARO), Volcani Centre, Rishon LeTsiyon 15159, Israel. [email protected].

DOI: 10.3390/molecules23102454