TY - JOUR T1 - Comprehensive assessment of functional effects of commonly used sweeteners on <em>ex vivo</em> human gut microbiome JF - bioRxiv DO - 10.1101/2022.01.15.474735 SP - 2022.01.15.474735 AU - Zhongzhi Sun AU - Wenju Wang AU - Leyuan Li AU - Xu Zhang AU - Zhibin Ning AU - Janice Mayne AU - Krystal Walker AU - Alain Stintzi AU - Daniel Figeys Y1 - 2022/01/01 UR - http://biorxiv.org/content/early/2022/01/16/2022.01.15.474735.abstract N2 - 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 StatementD.F. and A.S. have co-founded MedBiome, a clinical microbiome company. The remaining au-thors declare no competing interests. ER -