Revisited: Assessing the in vivo data on low/no-calorie sweeteners and the gut microbiota

Schiffman, Susan S.; Nagle, H. Troy

doi:10.1016/j.fct.2019.110692

Cited by 23 publications

(15 citation statements)

References 51 publications

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“…The oral administration of saccharin in rats (200–220 g weight), inhibited the growth of 6 bacterial strains (3 Lactobacillus species and 3 Escherichia coli strains) at doses of 107.0 mg and avoided the fermentation of glucose in the gut of these animals [19] . Interestingly, the oral administration of sucralose during a period of 12 weeks in the same murine model dramatically reduced the number of viable bifidobacteria, lactobacilli, clostridia and enterobacteria at 5 mg/kilogram/day [20] . Our findings suggested that hernandulcin is lesser toxic that saccharin and sucralose at least under in vitro conditions.…”

Section: Resultsmentioning

confidence: 99%

Hernandulcin Production in Cell Suspensions of Phyla Scaberrima: Exploring Hernandulcin Accumulation through Physical and Chemical Stimuli

Villa‐Ruano

Castro-Juárez

Lozoya‐Gloria

et al. 2021

Chemistry & Biodiversity

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Hernandulcin (HE) is a non‐caloric sweetener synthesized by the Mexican medicinal plant Phyla scaberrima. Herein we present the results of HE production through cell suspensions of P. scaberrima as well as the influence of pH, temperature, biosynthetic precursors and potential elicitors to enhance HE accumulation. The incorporation of mevalonolactone (30–400 mg L−1) farnesol (30–400 mg L−1), AgNO3 (0.025–0.175 M), cellulase (5–60 mg L−1; 0.3 units/mg), chitin (20–140 mg L−1) and (+)‐epi‐α‐bisabolol (300‐210 mg L−1) to the cell suspensions, resulted in a differential accumulation of HE and biomass. Among elicitors assayed, chitin, cellulase and farnesol increased HE production from 93.2 to ∼160 mg L−1 but, (+)‐epi‐α‐bisabolol (obtained by a synthetic biology approach) increased HE accumulation up to 182.7 mg L−1. HE produced by the cell suspensions was evaluated against nine strains from six species of gastrointestinal bacteria revealing moderate antibacterial activity (MIC, 214–465 μg mL−1) against Staphylococcus aureus, Escherichia coli and Helicobacter pylori. Similarly, HE showed weak toxicity against Lactobacillus sp. and Bifidobacterium bifidum (>1 mg mL−1), suggesting a selective antimicrobial activity on some species of gut microbiota. According to our results, chitin and (+)‐epi‐α‐bisabolol were the most effective molecules to enhance HE accumulation in cell suspensions of P. scaberrima.

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Section: Resultsmentioning

confidence: 99%

Hernandulcin Production in Cell Suspensions of Phyla Scaberrima: Exploring Hernandulcin Accumulation through Physical and Chemical Stimuli

Villa‐Ruano

Castro-Juárez

Lozoya‐Gloria

et al. 2021

Chemistry & Biodiversity

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“…A similar individual-specific response was also observed for sucralose (SUC), which has been shown by others to alter the composition of the gut microbiota in a rat model. 13,14 Although several sweeteners significantly changed the metaproteome of the gut microbiome, most sweeteners had limited effects on the biomass of the microbiome. Only ISO and thaumatin at 2 mg/ml (THA2) led to a biomass increase in all five microbiomes (Supplementary Figure S2).…”

Section: Discussionmentioning

confidence: 99%

“…demonstrated saccharin-induced glucose intolerance in healthy volunteers, and that these effects were transferable to germ-free mice through fecal transplantation. 11 To date, there have been no systematic studies on sweeteners for their effects on the microbiome Most of the studies were conducted using animal models and only focused on a few sweeteners, 11,13,14 and comparison across small-scale studies is challenging due to the variation of experimental approaches.…”

Section: Introductionmentioning

confidence: 99%

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

Sun

Wang

et al. 2022

Preprint

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The gut microbiome composition and function are associated with health and diseases. Sweeten-ers 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 sys-tematically 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 func-tional metaproteomics approach, improving our understanding of the roles of sweeteners on mi-crobiome-associated human health and disease issues.

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“…4 However, recent studies showed that sucralose may be metabolized under certain conditions. 5,6 Long-term sucralose consumption was even reported to induce weight loss, thus reducing the risk of diabetes, obesity, and other metabolic syndromes. 2,4,7 Therefore, accepted daily intake (ADI) of sucralose is currently 5 mg/kg body weight/day in the human according to Food and Drug Administration (FDA).…”

Section: ■ Introductionmentioning

confidence: 99%

“…Previously, sucralose was generally considered to be safe because most of it directly pass through the gastrointestinal tract . However, recent studies showed that sucralose may be metabolized under certain conditions. , Long-term sucralose consumption was even reported to induce weight loss, thus reducing the risk of diabetes, obesity, and other metabolic syndromes. ,, Therefore, accepted daily intake (ADI) of sucralose is currently 5 mg/kg body weight/day in the human according to Food and Drug Administration (FDA) . Nevertheless, the safe use of sucralose was rather unclear, especially regarding its use in foods and food processing.…”

Section: Introductionmentioning

confidence: 99%

Gut Microbiota and Its Metabolite Deoxycholic Acid Contribute to Sucralose Consumption-Induced Nonalcoholic Fatty Liver Disease

Shi

Chen

Cao

et al. 2021

J. Agric. Food Chem.

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As important signal metabolites within enterohepatic circulation, bile acids (BAs) play a pivotal role during the occurrence and development of diet-induced nonalcoholic fatty liver disease (NAFLD). Here, we evaluated the functional effects of BAs and gut microbiota contributing to sucralose consumption-induced NAFLD of mice. The results showed that sucralose consumption significantly upregulated the abundance of intestinal genera Bacteroides and Clostridium, which produced deoxycholic acid (DCA) accumulating in multiple biological matrixes including feces, serum, and liver of mice. Subsequently, elevated hepatic DCA, one of the endogenous antagonists of the farnesol X receptor (Fxr), inhibited hepatic gene expression including a small heterodimer partner (Shp) and Fxr leading to sucralose-induced NAFLD in mice. Dietary supplements with fructo-oligosaccharide or metformin markedly restored genera Bacteroides and Clostridium abundance and the DCA level of sucralose-consuming mice, which eventually ameliorated NAFLD. These findings highlighted the effects of gut microbiota and its metabolite DCA on sucralose-induced NAFLD of mice.

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Revisited: Assessing the in vivo data on low/no-calorie sweeteners and the gut microbiota

Cited by 23 publications

References 51 publications

Hernandulcin Production in Cell Suspensions of Phyla Scaberrima: Exploring Hernandulcin Accumulation through Physical and Chemical Stimuli

Hernandulcin Production in Cell Suspensions of Phyla Scaberrima: Exploring Hernandulcin Accumulation through Physical and Chemical Stimuli

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

Gut Microbiota and Its Metabolite Deoxycholic Acid Contribute to Sucralose Consumption-Induced Nonalcoholic Fatty Liver Disease

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