Comprehensive Assessment of Functional Effects of Commonly Used Sugar Substitute Sweeteners on Ex Vivo Human Gut Microbiome

Sun, Zhongzhi, Wang, Wenju, Li, Leyuan, Zhang, Xu, Ning, Zhibin, Mayne, Janice, Walker, Krystal, Stintzi, Alain and Figeys, Daniel (2022) Comprehensive Assessment of Functional Effects of Commonly Used Sugar Substitute Sweeteners on Ex Vivo Human Gut Microbiome. Microbiology Spectrum, 10 (4). ISSN 2165-0497

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Abstract

The composition and function of the human gut microbiome are often associated with health and disease status. Sugar substitute sweeteners are widely used food additives, although many studies using animal models have linked sweetener consumption to gut microbial changes and health issues. Whether sugar substitute 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 sugar substitute sweeteners, using an approach combining high-throughput in vitro microbiome culturing and metaproteomic analyses to quantify functional changes in different taxa. Hierarchical clustering based on metaproteomic responses of individual microbiomes resulted in two clusters. The noncaloric artificial sweetener (NAS) cluster was composed of NASs and two sugar alcohols with shorter carbon backbones (4 or 5 carbon atoms), and the carbohydrate (CHO) cluster was composed of the remaining sugar alcohols. The metaproteomic functional responses of the CHO cluster were clustered with those of the prebiotics fructooligosaccharides and kestose. The sugar substitute sweeteners in the CHO cluster showed the ability to modulate the metabolism of Clostridia. This study provides a comprehensive evaluation of the direct effects of commonly used sugar substitute sweeteners on the functions of the human gut microbiome using a functional metaproteomic approach, improving our understanding of the roles of sugar substitute sweeteners on microbiome-associated human health and disease issues.

Item Type:	Article
Additional Information:	Data availability. All raw data from the LC-MS/MS analyses have been deposited with the ProteomeXchange Consortium (http://www.proteomexchange.org) via the PRIDE partner repository (PXD030458).
Uncontrolled Keywords:	gut microbiome,metaproteomics,sugar substitute sweetener,physiology,ecology,immunology and microbiology(all),genetics,microbiology (medical),cell biology,infectious diseases ,/dk/atira/pure/subjectarea/asjc/1300/1314
Faculty \ School:	Faculty of Medicine and Health Sciences > Norwich Medical School
UEA Research Groups:	Faculty of Medicine and Health Sciences > Research Centres > Metabolic Health
Related URLs:	http://www.scopus.com/inward/record.url?...
Depositing User:	LivePure Connector
Date Deposited:	20 Mar 2026 15:30
Last Modified:	20 Mar 2026 15:30
URI:	https://ueaeprints.uea.ac.uk/id/eprint/102515
DOI:	10.1128/spectrum.00412-22

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