Non-caloric Artificial Sweeteners Research Articles

Sucralose: From Sweet Success to Metabolic Controversies-Unraveling the Global Health Implications of a Pervasive Non-Caloric Artificial Sweetener.

Sucralose is a food additive initially used to mitigate glycemic peaks and calorie intake in patients with diabetes and obesity. Although sucralose has been considered safe for human consumption, the World Health Organization (WHO) issued a global alert in 2023 concerning the potential health implications of this artificial sweetener. This review aims to comprehensively explore the effects of sucralose intake on human health by understanding sucralose absorption, metabolism, and excretion. We also outline the role of the sweet taste 1 receptor 3 (T1R3) in mediating sucralose-dependent signaling pathways that regulate satiety, incretin release, and insulin response. Finally, we discuss the impact of sucralose on microbiome dysbiosis, inflammatory response origin, liver damage, and toxicity. Gaining a deeper understanding of the manifold effects of sucralose on human physiology will help promote further studies to ensure its consumption is deemed safe for a broader population, including children, adolescents, and pregnant women.

A potential strategy against clinical carbapenem-resistant Enterobacteriaceae: antimicrobial activity study of sweetener-decorated gold nanoparticles in vitro and in vivo

BackgroundCarbapenem-resistant Enterobacteriaceae (CRE) present substantial challenges to clinical intervention, necessitating the formulation of novel antimicrobial strategies to counteract them. Nanomaterials offer a distinctive avenue for eradicating bacteria by employing mechanisms divergent from traditional antibiotic resistance pathways and exhibiting reduced susceptibility to drug resistance development. Non-caloric artificial sweeteners, commonly utilized in the food sector, such as saccharin, sucralose, acesulfame, and aspartame, possess structures amenable to nanomaterial formation. In this investigation, we synthesized gold nanoparticles decorated with non-caloric artificial sweeteners and evaluated their antimicrobial efficacy against clinical CRE strains.ResultsAmong these, gold nanoparticles decorated with aspartame (ASP_Au NPs) exhibited the most potent antimicrobial effect, displaying minimum inhibitory concentrations ranging from 4 to 16 µg/mL. As a result, ASP_Au NPs were chosen for further experimentation. Elucidation of the antimicrobial mechanism unveiled that ASP_Au NPs substantially elevated bacterial reactive oxygen species (ROS) levels, which dissipated upon ROS scavenger treatment, indicating ROS accumulation within bacteria as the fundamental antimicrobial modality. Furthermore, findings from membrane permeability assessments suggested that ASP_Au NPs may represent a secondary antimicrobial modality via enhancing inner membrane permeability. In addition, experiments involving crystal violet and confocal live/dead staining demonstrated effective suppression of bacterial biofilm formation by ASP_Au NPs. Moreover, ASP_Au NPs demonstrated notable efficacy in the treatment of Galleria mellonella bacterial infection and acute abdominal infection in mice, concurrently mitigating the organism's inflammatory response. Crucially, evaluation of in vivo safety and biocompatibility established that ASP_Au NPs exhibited negligible toxicity at bactericidal concentrations.ConclusionsOur results demonstrated that ASP_Au NPs exhibit promise as innovative antimicrobial agents against clinical CRE.Graphical

The impact of non-caloric artificial sweetener aspartame on female reproductive system in mice model

BackgroundArtificial sweeteners, used as sugar substitutes have found their ways into almost all the food items due to the notion that they are non-caloric. Aspartame is used in numerous food products throughout the world. The primary users of aspartame include diabetics and calorie conscious people who intend to limit their calorie intake.MethodsFemale Swiss albino mice were divided into three groups (12 mice each) for the duration of 30 and 60 days consecutively. The treatment groups received 40 mg/kg b. w. aspartame orally. Hormone assays using ELISA and tissue histopathology have been performed along with the fertility assay to access the treatment outcomeon the fertility of treated mice in comparison to controls.ResultsPresent study reports that female mice treated with aspartame for 30 and 60 days showed significant reduction in body weight, relative organ weight of (liver and kidney) and gonadosomatic index. These changes were more significantly recorded in 60 days treatment group. Aspartame treated animals for 30 and 60 days showed duration-dependent decrease gonandotropins (follicle stimulating hormone and luteinizing hormone), and steroids (estradiol and progesterone). Moreover, severe histopathological changes, reduction in number of growing follicles, degenerative changes in follicular structure, corona radiata and zonagranulosa were also observed. Besides, histomorphological changes were also observed in the uterine structure including atrophic uterine endometrial glands, contracted endometrial lining, disruption of the endometrial structure and the shapes of blood vessels were also altered.ConclusionNon-nutritive artificial sweeteners including aspartame negatively impact the function of ovaries and feedback mechanism of reproductive hormones by affecting the hypothalamic–pituitary–gonadal axis. In light of present findings the aspartame negatively impacted the reproductive system of female mice. More studies are required to identify the molecular mechanism and the pathways involved.

Non-caloric artificial sweeteners modulate conjugative transfer of multi-drug resistance plasmid in the gut microbiota

ABSTRACT Non-caloric artificial sweeteners have been widely permitted as table sugar substitutes with high intensities of sweetness. They can pass through the intestinal tract without significant metabolization and frequently encounter the gut microbiome, which is composed of diverse bacterial species and is a pool of antibiotic resistance genes (ARGs). However, little is known about whether these sweeteners could accelerate the spread of ARGs in the gut microbiome. Here, we established an in vitro conjugation model by using Escherichia coli that carries chromosome-inserted Tn7 lacIq-pLpp-mCherry and plasmid-encoded gfpmut3b gene as the donor and murine fecal bacteria as the recipient. We found that four commonly used artificial sweeteners (saccharin, sucralose, aspartame, and acesulfame potassium) can increase reactive oxygen species (ROS) production and promote plasmid-mediated conjugative transfer to the gut microbiome. Cell sorting and 16S rRNA gene amplicon sequencing analysis of fecal samples reveal that the tested sweeteners can promote the broad-host-range plasmid permissiveness to both Gram-negative and Gram-positive gut bacteria. The increased plasmid permissiveness was also validated with a human pathogen Klebsiella pneumoniae. Collectively, our study demonstrates that non-caloric artificial sweeteners can induce oxidative stress and boost the plasmid-mediated conjugative transfer of ARGs among the gut microbiota and a human pathogen. Considering the soaring consumption of these sweeteners and the abundance of mobile ARGs in the human gut, our results highlight the necessity of performing a thorough risk assessment of antibiotic resistance associated with the usage of artificial sweeteners as food additives.

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

ABSTRACTThe 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.IMPORTANCE The human gut microbiome is closely related to human health. Sugar substitute sweeteners as commonly used food additives are increasingly consumed and have potential impacts on microbiome functionality. Although many studies have evaluated the effects of a few sweeteners on gut microbiomes using animal models, the direct effect of sugar substitute sweeteners on the human gut microbiome remains largely unknown. Our results revealed that the sweetener-induced metaproteomic responses of individual microbiomes had two major patterns, which were associated with the chemical properties of the sweeteners. This study provided a comprehensive evaluation of the effects of commonly used sugar substitute sweeteners on the human gut microbiome.

Non-caloric artificial sweeteners exhibit antimicrobial activity against bacteria and promote bacterial evolution of antibiotic tolerance

Non-caloric artificial sweeteners are being widely used as safe table sugar substitutes with highly intensive sweetness but low calories. Previous studies have suggested that some of the sweeteners can alter the gut microbiota composition and promote horizontal transfer of antibiotic resistance genes across bacterial genera. However, little is known about whether these sweeteners could show antibiotic-like antimicrobial activity against bacteria, especially gut relevant bacteria. Whether they could affect evolutional trajectory of antibiotic resistance or tolerance in bacteria is also not clear yet. Here we investigated four commonly used artificial sweeteners (saccharin, sucralose, aspartame, and acesulfame potassium) against both Gram-negative (Escherichia coli and Klebsiella pneumoniae) and positive (Bacillus subtilis) strains. Results show that all four sweeteners exhibit antimicrobial effects on these strains. The antimicrobial mechanism is due to increased reactive oxygen species (ROS) and cell envelope damage. Compared to sucrose and glucose, the treatment of artificial sweeteners stimulates bacterial efflux pumps and promotes bacterial evolution of antibiotic tolerance. Collectively, our finding provides insights into roles of artificial sweeteners in the emergence of antibiotic tolerance and calls for a re-evaluation of risks due to their intensive usage.

Effects of non‐caloric artificial sweeteners on naïve and dextran sodium sulfate‐exposed Drosophila melanogaster

AbstractSaccharin and sucralose are worldwide used tabletop non‐caloric artificial sweeteners (NAS), and although they are considered metabolically inert and safe for consumption, recent studies observed an NAS‐mediated modulation of the intestinal microbiota, which may result in the development of intestinal inflammatory diseases. The present study investigated the effects of NAS alone and in combination with dextran sodium sulfate (DSS), a chemical known to induce gut inflammation, on parameters of overall fitness including longevity and climbing ability of female Drosophila melanogaster. DSS‐exposed flies were subjected to saccharin or sucralose, and their effects on survival and the gene expression levels of different antimicrobial peptides (AMPs) were assessed. Saccharin supplementation significantly increased the lifespan of D. melanogaster, while DSS significantly decreased the survival in a dose‐dependent manner. Additionally, DSS exposure of flies resulted in a trend toward an up‐regulation of the mRNA levels of the AMPs, drosocin and metchnikowin. This effect was more pronounced in the NAS‐supplemented group reaching significance. This may indicate that NAS supplementation improves intestinal immune reactions during an inflammatory metabolic state.

Acesulfame potassium induces dysbiosis and intestinal injury with enhanced lymphocyte migration to intestinal mucosa.

The artificial sweetener acesulfame potassium (ACK) is officially approved as safe for intake and has been used in processed foods. However, ACKs have been reported to induce metabolic syndrome, along with alteration of the gut microbiota in mice. In recent years, studies have suggested that this artificial sweetener promotes myeloperoxidase reactivity in Crohn's disease-like ileitis. We aimed to investigate the effect of ACK on the intestinal mucosa and gut microbiota of normal mice. Acesulfame potassium was administered to C57BL/6J mice (8weeks old) via free drinking. Intestinal damage was evaluated histologically, and messenger RNA (mRNA) levels of TNF-α, IFN-γ, IL1-β, MAdCAM-1, GLP1R, and GLP2R were determined with quantitative reverse transcription polymerase chain reaction (qRT-PCR). Immunohistochemistry was performed to examine the expression of MAdCAM-1 in the small intestine. The composition of gut microbiota was assessed using high-throughput sequencing. We performed intravital microscopic observation to examine if ACK altered lymphocyte migration to the intestinal microvessels. Acesulfame potassium increased the expression of proinflammatory cytokines, decreased the expression of GLP-1R and GLP-2R, and induced small intestinal injury with an increase in intestinal permeability, and ACK treatment induced microbial changes, but the transfer of feces alone from ACK mice did not reproduce intestinal damage in recipient mice. ACK treatment significantly increased the migration of lymphocytes to intestinal microvessels. Acesulfame potassium induces dysbiosis and intestinal injury with enhanced lymphocyte migration to intestinal mucosa. Massive use of non-caloric artificial sweeteners may not be as safe as we think.

Phenotyping Aquatic Neurotoxicity Induced by the Artificial Sweetener Saccharin at Sublethal Concentration Levels.

Artificial sweeteners (ASs) have generally been applied as food additives to improve the taste of sweetness. Thus, their potential toxic effects have received extensive attention. Saccharin (SAC), discovered more than a century ago, has been used as the first noncaloric AS in foods and beverages for over 100 years. Although the toxicological effects such as carcinogenicity of SAC have been controversial for a long time, there is a paucity of knowledge covering its potential behavioral toxicity and neurotoxicity. Methodologically, in current research, adult zebrafish neurobehavioral phenotypic screening approaches were introduced to systematically delineate the potential behavioral and neural toxicity of SAC by phenotyping the comprehensive neuro-behavioral profiles of adult zebrafish, which were chronically (2 months) subject to SAC (0, 1, 10, and 50 mg/L) exposure. Subsequently, a cohort of standard neurobehavioral tests including the light/dark preference (LDP) test, novel tank diving (NTD) test, novel object recognition (NOR) test, social interaction test (SIT), color-associated learning and memory test, and conditional place preference test were applied to delineate the general adverse effect of SAC. Specifically, in a concentration-dependent manner, SAC significantly increased the preference toward the dark side in the LDP test, inhibited exploratory behavior to the top arena in the NTD test, dampened the motivation to explore the novel object in the NOR test, weakened social preference in the SIT, and interfered in the color-based associative learning and memory ability. For example, in the LDP test, SAC remarkably increased the swimming distance of zebrafish in the dark part from 222 ± 34.6 (control group) to 675 ± 35.0 (50 mg/L group). Finally, the quantity of certain key neurotransmitters was further measured to determine the alteration induced by SAC on the brain chemistry. In total, the current research would provide a versatile neurobehavioral phenomics-based strategy to phenotypically screen the neurotoxicity of food additives at the overall animal level and provide a reference for further neurotoxicity exploration at the tissue and molecular level.

Sucralose Stimulates Mitochondrial Bioenergetics in Caco-2 Cells.

Sucralose is a non-caloric artificial sweetener widely used in processed foods that reportedly affects energy homeostasis through partially understood mechanisms. Mitochondria are organelles fundamental for cellular bioenergetics that are closely related to the development of metabolic diseases. Here, we addressed whether sucralose alters mitochondrial bioenergetics in the enterocyte cell line Caco-2. Sucralose exposure (0.5–50 mM for 3–24 h) increased cellular reductive power assessed through MTT assay, suggesting enhanced bioenergetics. Low doses of sucralose (0.5 and 5 mM) for 3 h stimulated mitochondrial respiration, measured through oxygraphy, and elevated mitochondrial transmembrane potential and cytoplasmic Ca2+, evaluated by fluorescence microscopy. Contrary to other cell types, the increase in mitochondrial respiration was insensitive to inhibition of mitochondrial Ca2+ uptake. These findings suggest that sucralose alters enterocyte energy homeostasis, contributing to its effects on organismal metabolism.

Harnessing the gut microbiota to promote metabolic health.

Precision medicine has become the mainstay of modern therapeutics, especially for neoplastic disease, but this paradigm does not commonly prevail in dietary planning. Compelling evidence suggests that individual features, including the structure and function of the gut microbiota, contribute to harvesting and metabolizing energy from food, and thereby modulate the host metabolic phenotype and glucose homeostasis. Here, the concept of precision to dietary planning is highlighted by demonstrating the role of the microbiota in glucose intolerance in response to noncaloric artificial sweeteners, and by linking the microbiota and other host features to postprandial increases in blood glucose. These findings highlight the heterogeneity that exists among humans, which translates into divergent metabolic responses to similar food and warrants the adoption of next-generation sequencing technologies and advanced bioinformatics to revolutionize nutrition studies, laying the groundwork for an individually focused tailor-made practice.

NMR based real-time enzyme kinetics on estimating the inhibitory effect of sucralose in the enzymatic conversion of sucrose

Sucralose, one of the popular non-caloric artificial sweeteners, has been known to influence the enzymatic conversion of sucrose to glucose and fructose by invertase. In continuing the use of real-time NMR experiments and reaction progress curve analysis to measure enzyme kinetics, here we investigate the role of sucralose as an inhibitor. NMR based kinetic experiments were performed as a function of the substrate concentration for a range of sucralose concentrations, and the results were analyzed by fitting the progress curve to the Lambert-W function. The Michaelis-Menten parameters were then used to estimate the inhibitory constant of sucralose. To estimate the extent of sucralose inhibition on the enzymatic production of glucose, control experiments were performed with lactose as the inhibitor under similar experimental conditions. The results show that sucralose is a much more potent inhibitor than lactose, inhibiting the enzymatic conversion at least seven times more.

Saccharin Supplementation Inhibits Bacterial Growth and Reduces Experimental Colitis in Mice.

Non-caloric artificial sweeteners are frequently discussed as components of the “Western diet”, negatively modulating intestinal homeostasis. Since the artificial sweetener saccharin is known to depict bacteriostatic and microbiome-modulating properties, we hypothesized oral saccharin intake to influence intestinal inflammation and aimed at delineating its effect on acute and chronic colitis activity in mice. In vitro, different bacterial strains were grown in the presence or absence of saccharin. Mice were supplemented with saccharin before or after induction of acute or chronic colitis using dextran sodium sulfate (DSS) and the extent of colitis was assessed. Ex vivo, intestinal inflammation, fecal bacterial load and composition were studied by immunohistochemistry analyses, quantitative PCR, 16 S RNA PCR or next generation sequencing in samples collected from analyzed mice. In vitro, saccharin inhibited bacterial growth in a species-dependent manner. In vivo, oral saccharin intake reduced fecal bacterial load and altered microbiome composition, while the intestinal barrier was not obviously affected. Of note, DSS-induced colitis activity was significantly improved in mice after therapeutic or prophylactic treatment with saccharin. Together, this study demonstrates that oral saccharin intake decreases intestinal bacteria count and hence encompasses the capacity to reduce acute and chronic colitis activity in mice.

Effects of Chronic Artificial Sweetener Consumption on Type 1 Diabetes Susceptibility

As the diabetes epidemic grows worldwide, there is a heightened awareness of how modern day diets may contribute to the increased incidence of disease. To combat the dietary intake of sugar, there has been a drastic increase in the daily consumption of non‐caloric artificial sweeteners (NCAS). However, a number of studies suggest that NCAS cause counterintuitive metabolic derangements that may contribute to negative health outcomes. Conversely, there are limited duration studies focused on weight management suggesting the opposite, thus creating controversy. The impact of chronic NCAS consumption in type 1 diabetes (T1D) patients or those with a high genetic susceptibility for T1D is also unknown. T1D has a strong genetic basis; however, environmental factors likely underlie the rapid increase in T1D incidence in the past few decades. Children with T1D frequently consume NCAS as a way of managing postprandial hyperglycemia and insulin doses. Increased availability of NCAS within the home likely also translates to more NCAS consumption by non‐diabetic siblings with a higher risk to develop T1D. Our study aimed to test the effects of chronic consumption of NCAS subtypes on high T1D susceptibility backgrounds. To test this, we supplemented the diet of T1D susceptible BioBreeding DR+/+ rats with aspartame (metabolized) and acesulfame potassium (Ace‐K+, not metabolized) for three weeks in their drinking water. DR+/+ rats consuming NCAS water had a significant increase in blood glucose versus normal water controls. Metabolomics analysis of plasma from these rats revealed alterations in lipid and energy metabolism, with a greater effect resulting from Ace‐K+. Using a novel mass spectrometry‐based quantification assay we developed, we found that Ace‐K+ also accumulated in the plasma these DR+/+ rats (21+10 μM; N=6) following chronic consumption. Further follow‐up was performed in vitro using rat cardiac microvascular endothelial cells (RCMVECs) to measure cardiometabolic effects. The RCMVECs were treated with an Ace‐K+ dose‐response for three weeks and they exhibited impairment during in vitro tube formation and cell viability tests (p<0.05; N=3). Gene expression analysis of the RCMVECs displayed significant differences in insulin signaling, glucose metabolism, and inflammatory regulation (p<0.05; N=4). In further tests, we also observed that chronic Ace‐K+ consumption accelerated the rate of type 1 diabetes onset in DRlyp/lyp rats. Overall, these results suggest that the accumulation of absorbed intact NCAS subtypes, like Ace‐K+, have the potential to lead to metabolic flux that may be important in pre‐ and post‐onset T1D, whereas the metabolized aspartame caused less fluctuation. We are now focused on translating these studies to a pediatric T1D population and are implementing a novel NCAS food frequency questionnaire and plasma quantification test to better measure consumption clinically.Support or Funding InformationSupport for this project was provided by the Medical College of Wisconsin Clinical and Translational Science Institute, the Mayo Clinic Metabolomics Resource Core (pilot award provided by the U24DK100469 grant to BRH), and the Children’s Research Institute (CRI19301 to MH).

Associations of diet soda and non-caloric artificial sweetener use with markers of glucose and insulin homeostasis and incident diabetes: the Strong Heart Family Study.

Background/Objectives:Non-caloric artificial sweeteners (NAS) are marketed as healthier alternatives to sugar, but the relationship between consumption of NAS and development of diabetes is unclear. This study assessed the associations of diet soda and NAS consumption with: (1) early markers of insulin and glucose homeostasis (cross-sectionally); and (2) incident diabetes (over an average of 8 years of follow-up) among American Indians, a population with high rates of obesity.Subjects/Methods:The study population included Strong Heart Family Study participants without cardiovascular disease or diabetes who participated in the 2007-2009 study exam (n=1,359). Diet soda and NAS consumption were assessed using a Block food frequency questionnaire and supplemental NAS questionnaire at the study exam. Fasting plasma glucose and insulin were measured during the study exam after a 12-hour overnight fast. Participants were followed for incident diabetes through December 2017 using a single phone interview and medical record review; diabetes was identified by self-report and confirmed by documentation in medical records. Associations of diet soda and NAS consumption with fasting insulin, glucose and incident diabetes were assessed using generalized estimating equations (fasting insulin and glucose analyses) and parametric survival models with Weibull distributions (incident diabetes analyses).Results:Just under half of participants reported regularly consuming diet soda (40%) or using NAS to sweeten their beverages (41%). During an average 8 years of follow-up, we identified 98 cases of incident diabetes. After correction for multiple comparisons, there were no statistically significant associations of reported diet soda and NAS consumption with fasting insulin, fasting glucose, or incident diabetes.Conclusions:Although reported consumption of diet soda and NAS were high, neither were associated with diabetes risk.

Stability of individual differences in sucralose taste preference.

Outbred rats display variable preferences for bittersweet solutions, expressed as preference or avoidance of high concentrations of artificial sweeteners over water. This may reflect individual differences in appetitive/aversive conflict processing that may have predictive validity for disorders of motivation. Here we use a homecage two-bottle choice procedure to examine the test/retest stability and between-tastant consistency in sucralose preference to determine the reliability of bittersweet taste preference. Sucralose is a non-caloric artificial sweetener that is preferred by some rats and avoided by others. We sought to determine whether sucralose preference is consistent with preference of sucrose/quinine solutions that have known sweet and bitter taste qualities, respectively. We give fluid restricted rats 45-minutes homecage access to water and ascending concentrations of sucralose (SUCRA; 0.0025-10mM) or a compound solution of sucrose (116mM) + quinine (0.002-2mM) (SQ). We use a within-subject counterbalanced design (SUCRA or SQ testing) to determine preference of each bittersweet solution relative to water. We observed individual variability in preference for SUCRA and SQ, such that some rats preferred bittersweet solutions over water (preferring) while other rats preferred water over bittersweet solutions (avoiding). Within tastant, this preference remained stable across repeated testing. Between solutions, SUCRA preference scores correlated with SQ scores, suggesting consistent taste conflict processing for both bittersweet solutions. Population level analyses confirmed that preference generalizes across bittersweet solutions, and that rats’ preferences for bittersweet solutions relative to water are stable over time. The test/retest and between-tastant reliability of this taste conflict screening procedure support the potential utility of this model for exploring individual variability in appetitive/aversive conflict processes mediating motivated behavior.

Sucrose and saccharin differentially modulate depression and anxiety-like behavior in diabetic mice: exposures and withdrawal effects.

Sugar has addictive potential owing to increase in monoaminergic-transmission at pleasure and reward centers of brain. Insulin dysfunction triggered synaptic monoamine deficit is associated with sugar overeating and craving-related psychological changes in diabetic patients. Sugar-substitute (saccharin) is non-caloric artificial sweetener that may alleviate brain disorders in diabetes. In present study, effects of sucrose and sugar-substitute (saccharin) exposures and withdrawal on depression and anxiety-like behavior in type 2 diabetic mice were assessed. Swiss albino mice were injected with streptozotocin (135mg/kg). After induction of diabetes, mice were exposed to a two-bottle water-water, 10% sucrose-water, or 10% saccharin-water choice paradigm for 28days. Separate groups were employed to assess withdrawal effect of sucrose or saccharin in diabetic mice. Monoamine oxidase (MAO), corticosterone, thiobarbituric acid reactive substances (TBARS), and reduced glutathione (GSH) were quantified after behavioral tests. Diabetic mice manifested preference towards 10% sucrose or saccharin over water. Sucrose-overeating by diabetic mice amplified symptoms of depression and anxiety; however, withdrawal further exaggerated these behavioral abnormalities. Substitution of sucrose by 10% saccharin attenuated the depressive and anxiety-like behavior in comparison to diabetic mice that were exposed separately to water-water or sucrose-water alone, and with respect to normal mice. Although withdrawal from saccharin resurfaced behavioral anomalies in diabetic mice, however, these were significantly low in comparison with withdrawal from sucrose or normal group. Reinstatement of exposure to saccharin mitigated symptoms of depression and anxiety in diabetic mice. Preference of sucrose overeating augments while saccharin mitigates depressive and anxiety behavior during diabetes.

A Single 48 mg Sucralose Sip Unbalances Monocyte Subpopulations and Stimulates Insulin Secretion in Healthy Young Adults.

Sucralose is a noncaloric artificial sweetener that is widely consumed worldwide and has been associated with alteration in glucose and insulin homeostasis. Unbalance in monocyte subpopulations expressing CD11c and CD206 hallmarks metabolic dysfunction but has not yet been studied in response to sucralose. Our goal was to examine the effect of a single sucralose sip on serum insulin and blood glucose and the percentages of classical, intermediate, and nonclassical monocytes in healthy young adults subjected to an oral glucose tolerance test (OGTT). This study was a randomized, placebo-controlled clinical trial. Volunteers randomly received 60 mL water as placebo (n = 20) or 48 mg sucralose dissolved in 60 mL water (n = 25), fifteen minutes prior to an OGTT. Blood samples were individually drawn every 15 minutes for 180 minutes for quantifying glucose and insulin concentrations. Monocyte subsets expressing CD11c and CD206 were measured at -15 and 180 minutes by flow cytometry. As compared to controls, volunteers receiving sucralose exhibited significant increases in serum insulin at 30, 45, and 180 minutes, whereas blood glucose values showed no significant differences. Sucralose consumption caused a significant 7% increase in classical monocytes and 63% decrease in nonclassical monocytes with respect to placebo controls. Pearson's correlation models revealed a strong association of insulin with sucralose-induced monocyte subpopulation unbalance whereas glucose values did not show significant correlations. Sucralose ingestion decreased CD11c expression in all monocyte subsets and reduced CD206 expression in nonclassical monocytes suggesting that sucralose does not only unbalance monocyte subpopulations but also alter their expression pattern of cell surface molecules. This work demonstrates for the first time that a 48 mg sucralose sip increases serum insulin and unbalances monocyte subpopulations expressing CD11c and CD206 in noninsulin-resistant healthy young adults subjected to an OGTT. The apparently innocuous consumption of sucralose should be reexamined in light of these results.

Effects of single and combined toxic exposures on the gut microbiome: Current knowledge and future directions

Human populations are chronically exposed to mixtures of toxic chemicals. Predicting the health effects of these mixtures require a large amount of information on the mode of action of their components. Xenobiotic metabolism by bacteria inhabiting the gastrointestinal tract has a major influence on human health. Our review aims to explore the literature for studies looking to characterize the different modes of action and outcomes of major chemical pollutants, and some components of cosmetics and food additives, on gut microbial communities in order to facilitate an estimation of their potential mixture effects.We identified good evidence that exposure to heavy metals, pesticides, nanoparticles, polycyclic aromatic hydrocarbons, dioxins, furans, polychlorinated biphenyls, and non-caloric artificial sweeteners affect the gut microbiome and which is associated with the development of metabolic, malignant, inflammatory, or immune diseases.Answering the question ‘Who is there?’ is not sufficient to define the mode of action of a toxicant in predictive modeling of mixture effects. Therefore, we recommend that new studies focus to simulate real-life exposure to diverse chemicals (toxicants, cosmetic/food additives), including as mixtures, and which combine metagenomics, metatranscriptomics and metabolomic analytical methods achieving in that way a comprehensive evaluation of effects on human health.

Immobilization of enzymes into nanofiber membranes via electrospinning and its application in natural sweetener production

Non-caloric artificial sweeteners (NAS) are currently the world's most widely used food additives, which are considered safe and contributed to good health. But recent research shows that there are still controversies. Therefore, natural sweeteners had gained much attention as NAS substitutes. Recently, the fastest growing market of natural sweetener is the sweeteners made from monk fruit, because its extracts are highest in sweetness among various natural sweeteners and parts of the sweetness compounds have significant anti-diabetic activity. However, one of the components in monk fruit extracts called Siamenoside I (S I), which found to be the most sweetness compound and taste most closely to sucrose, are relatively low in contents. In addition, the Mogroside III E (MG III E), which is lower in sweetness compared to S I but with significant anti-diabetic properties, are also low in contents in the natural monk fruit extracts. As the results, the developing of methods to enrich the contents of S I and MG III E in monk fruit extracts and related products are the goals for the current natural sweetener manufacturers. The bitter tastes and flavors of saponins containing functional foods and related beverages are still the issues to be addressed. For example, the modification of glycoside linkage patterns of saponins including oleuropeins, ginsenosides, and momordicosides could achieve the debittering purpose and meet the consumers' preferences. Therefore, the goals of this research are to immobilize specific enzymes using electrospinning. Together with the high throughput microreactor, and the continuous packed-bed column, we suppose that we could obtain a fair amount of S I and MG III E through enzyme transformation of MG V and improve the taste of monk fruit extracts as natural sweeteners. Support or Funding Information This research was supported by the by the National Science Council of Taiwan (NSC Grant 106-2218-E-029-002-MY2). The screening of yeast transformants having its exg1Δ::kanMX4 replaced by DbExg1-His-URA3 cassette which has S I bioconversion activity A. Ura− and G418 resistance selection. B. The genotype confirmation of yeast transformants. Successful transformants have 3523 b.p product. Numbers represent candidates relative to candidates in A. C. Screening of transformants with siamenoside I production specificity. Peak 1, mogroside V; 2, siamenoside I; 3, mogroside IV; 4, mogroside IIIE. SEM images and size distribution of electrospun nanofibrous membrane: (Upper panel) PVA; (Lower panel) cross-lined PVA. SEM images and size distribution of electrospun nanofibrous membrane: (Upper panel) PVA with 0.5% of the enzyme; (Lower panel) cross-lined PVA with 0.5% of the enzyme. SEM images and size distribution of electrospun nanofibrous membrane: (Upper panel) PVA with 2.0 % of the enzyme; (Lower panel) cross-lined PVA with 2.0% of the enzyme. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.