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Comprehensive assessment of functional effects of commonly used sweeteners on ex vivo human gut microbiome

Zhongzhi Sun, Wenju Wang, Leyuan Li, Xu Zhang, Zhibin Ning, Janice Mayne, Krystal Walker, Alain Stintzi, Daniel Figeys
doi: https://doi.org/10.1101/2022.01.15.474735
Zhongzhi Sun
aSchool of Pharmaceutical Sciences, Faculty of Medicine, University of Ottawa, Ottawa, ON, K1H 8M5, Canada
bShanghai Institute of Materia Medica-University of Ottawa Joint Research Center in Systems and Personalized Pharmacology and Ottawa Institute of Systems Biology, University of Ottawa, Ottawa, ON, K1H 8M5, Canada
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Wenju Wang
aSchool of Pharmaceutical Sciences, Faculty of Medicine, University of Ottawa, Ottawa, ON, K1H 8M5, Canada
bShanghai Institute of Materia Medica-University of Ottawa Joint Research Center in Systems and Personalized Pharmacology and Ottawa Institute of Systems Biology, University of Ottawa, Ottawa, ON, K1H 8M5, Canada
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Leyuan Li
aSchool of Pharmaceutical Sciences, Faculty of Medicine, University of Ottawa, Ottawa, ON, K1H 8M5, Canada
bShanghai Institute of Materia Medica-University of Ottawa Joint Research Center in Systems and Personalized Pharmacology and Ottawa Institute of Systems Biology, University of Ottawa, Ottawa, ON, K1H 8M5, Canada
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Xu Zhang
aSchool of Pharmaceutical Sciences, Faculty of Medicine, University of Ottawa, Ottawa, ON, K1H 8M5, Canada
bShanghai Institute of Materia Medica-University of Ottawa Joint Research Center in Systems and Personalized Pharmacology and Ottawa Institute of Systems Biology, University of Ottawa, Ottawa, ON, K1H 8M5, Canada
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Zhibin Ning
aSchool of Pharmaceutical Sciences, Faculty of Medicine, University of Ottawa, Ottawa, ON, K1H 8M5, Canada
bShanghai Institute of Materia Medica-University of Ottawa Joint Research Center in Systems and Personalized Pharmacology and Ottawa Institute of Systems Biology, University of Ottawa, Ottawa, ON, K1H 8M5, Canada
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Janice Mayne
aSchool of Pharmaceutical Sciences, Faculty of Medicine, University of Ottawa, Ottawa, ON, K1H 8M5, Canada
bShanghai Institute of Materia Medica-University of Ottawa Joint Research Center in Systems and Personalized Pharmacology and Ottawa Institute of Systems Biology, University of Ottawa, Ottawa, ON, K1H 8M5, Canada
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Krystal Walker
aSchool of Pharmaceutical Sciences, Faculty of Medicine, University of Ottawa, Ottawa, ON, K1H 8M5, Canada
bShanghai Institute of Materia Medica-University of Ottawa Joint Research Center in Systems and Personalized Pharmacology and Ottawa Institute of Systems Biology, University of Ottawa, Ottawa, ON, K1H 8M5, Canada
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Alain Stintzi
aSchool of Pharmaceutical Sciences, Faculty of Medicine, University of Ottawa, Ottawa, ON, K1H 8M5, Canada
cDepartment of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON, K1H 8M5, Canada
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Daniel Figeys
aSchool of Pharmaceutical Sciences, Faculty of Medicine, University of Ottawa, Ottawa, ON, K1H 8M5, Canada
bShanghai Institute of Materia Medica-University of Ottawa Joint Research Center in Systems and Personalized Pharmacology and Ottawa Institute of Systems Biology, University of Ottawa, Ottawa, ON, K1H 8M5, Canada
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  • For correspondence: dfigeys@uottawa.ca
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Abstract

The gut microbiome composition and function are associated with health and diseases. Sweeteners are widely used food additives, although many studies using animal models have linked sweetener consumption to gut microbial changes and health issues. Whether sweeteners directly change the human gut microbiome functionality remains largely unknown. In this study, we systematically investigated the responses of five human gut microbiomes to 21 common sweeteners, using an approach combining high-throughput ex vivo microbiome culturing and metaproteomics to quantify functional changes in different taxa. Hierarchical clustering based on metaproteomic responses of individual microbiomes resulted in two clusters. The first cluster was composed of non-caloric artificial sweeteners (NAS) and two sugar alcohols with shorter carbon backbones (4-5 carbon atoms), and the second cluster was composed of sugar alcohols with longer carbon backbones. The metaproteomic functional responses of the second cluster were similar to the prebiotic fructooligosaccharides and kestose, indicating that these sugar alcohol-type sweeteners have potential prebiotic functions. This study provides a comprehensive evaluation of the direct effects of commonly used sweeteners on the functions of the human gut microbiome using a functional metaproteomics approach, improving our understanding of the roles of sweeteners on microbiome-associated human health and disease issues.

Competing Interest Statement

D.F. and A.S. have co-founded MedBiome, a clinical microbiome company. The remaining au-thors declare no competing interests.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted January 16, 2022.
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Comprehensive assessment of functional effects of commonly used sweeteners on ex vivo human gut microbiome
Zhongzhi Sun, Wenju Wang, Leyuan Li, Xu Zhang, Zhibin Ning, Janice Mayne, Krystal Walker, Alain Stintzi, Daniel Figeys
bioRxiv 2022.01.15.474735; doi: https://doi.org/10.1101/2022.01.15.474735
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Comprehensive assessment of functional effects of commonly used sweeteners on ex vivo human gut microbiome
Zhongzhi Sun, Wenju Wang, Leyuan Li, Xu Zhang, Zhibin Ning, Janice Mayne, Krystal Walker, Alain Stintzi, Daniel Figeys
bioRxiv 2022.01.15.474735; doi: https://doi.org/10.1101/2022.01.15.474735

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