Comparison of a Daily Steviol Glycoside Beverage compared with a Sucrose Beverage for Four Weeks on Gut Microbiome in Healthy Adults.

BACKGROUND: Recent studies suggest that some nonnutritive sweeteners (NNS) have deleterious effects on the human gut microbiome (HGM). The effect of steviol glycosides on the HGM has not been well studied. OBJECTIVE: We aimed to evaluate the effects of stevia- compared with sucrose-sweetened beverages on the HGM and fecal short-chain fatty acid (SCFA) profiles. METHODS: Using a randomized, double-blinded, parallel-design study, n = 59 healthy adults [female/male, n = 36/23, aged 31±9 y, body mass index (BMI): 22.6±1.7 kg/m2] consumed 16 oz of a beverage containing either 25% of the acceptable daily intake (ADI) of stevia or 30 g of sucrose daily for 4 weeks followed by a 4-week washout. At weeks 0 (baseline), 4, and 8, the HGM was characterized via shotgun sequencing, fecal SCFA concentrations were measured using ultra-high performance liquid chromatography-tandem mass spectrometry and anthropometric measurements, fasting serum glucose, insulin and lipids, blood pressure, pulse, and 3-d diet records were obtained. RESULTS: There were no significant differences in the HGM or fecal SCFA between the stevia and sucrose groups at baseline (P > 0.05). At week 4 (after intervention), there were no significant differences in the HGM at the phylum, family, genus, or species level between the stevia and sucrose groups and no significant differences in fecal SCFA. At week 4, BMI had increased by 0.3 kg/m2 (P = 0.013) in sucrose compared with stevia, but all other anthropometric and cardiometabolic measures and food intake did not differ significantly (P > 0.05). At week 8 (after washout), there were no significant differences in the HGM, fecal SFCA, or any anthropometric or cardiometabolic measure between the stevia and sucrose groups (P > 0.05). CONCLUSIONS: Daily consumption of a beverage sweetened with 25% of the ADI of stevia for 4 weeks had no significant effects on the HGM, fecal SCFA, or fasting cardiometabolic measures, compared with daily consumption of a beverage sweetened with 30 g of sucrose. TRIAL REGISTRATION: clinicaltrials.gov as NCT05264636.

Comparative In vitro metabolism of purified mogrosides derived from monk fruit extracts.

Mogrosides are the primary components responsible for the sweet taste of Monk fruit which is derived from Siraitia grosvenorii (Swingle), a herbaceous plant native to southern China. Many mogrosides have been identified from Monk fruit extract, but the major sweetness component of Monk fruit by mass is mogroside V, comprising up to 0.5% of the dried fruit weight. Recent pharmacokinetic studies indicate that the parent mogrosides undergo minimal systemic absorption following ingestion and hydrolysis by digestive enzymes and/or intestinal flora and are excreted as mogrol (i.e., the aglycone) and its mono- and diglucosides. The objective of this study was to demonstrate whether individual mogrosides, are metabolized to a common and terminal deglycosylated metabolite, mogrol. An in vitro assay was conducted with pooled human male and female intestinal fecal homogenates (HFH) using mogrosides IIIe, mogroside V, siamenoside I, and isomogroside V at two concentrations over a 48 h period. The results show that various mogrosides that differ in the linkages and number of glucose units attached to a common cucurbitane backbone, share a common metabolic fate, and are metabolized within 24 h to mogrol. Aside from an apparent difference in the initial rate of deglycosylation between mogrosides at higher concentrations, no apparent difference in the rate of deglycosylation was observed between the male and female HFH. Given the similar structures of these mogrosides and a shared metabolic fate to mogrol, the study provides support for a reasonably conservative approach to assess safety based on bridging safety data from an individual mogroside (i.e., Mogroside V) to other mogrosides, and the establishment of a group Acceptable Daily Intake (ADI), rather than individual ADI's for mogrosides.

Metabolic fate in adult and pediatric population of steviol glycosides produced from stevia leaf extract by different production technologies.

More than 60 naturally occurring steviol glycosides in the Stevia rebaudiana Bertoni plant share a similar molecular structure with an aglycone steviol backbone conjugated with ß- and α-glycosidic bonds to different sugar moieties. These glycosides are naturally produced in different quantities within the stevia leaf. Certain minor glycosides with superior sensory attributes, such as Reb D and Reb M, are found less than 0.1% in traditional stevia leaves. New technologies can now produce better tasting steviol glycosides by using enzymatic conversion of stevioside and Reb A, which are abundant in stevia leaf. Several regulatory authorities recently evaluated steviol glycosides produced by enzymatic conversion of stevia leaf extract and approved them safe for human consumption. Steviol glycosides undergo microbial hydrolysis in the colon to generate steviol, which is absorbed and metabolized into steviol glucuronide, and excreted primarily via human's urine. Previous studies have shown the hydrolysis of highly purified individual steviol glycosides extracted from stevia leaf are converted to steviol in the presence of colonic microbiota of adults. Since colonic microbiota of children may be different from adults, this study investigates the metabolic fate in the colonic microbiota of adults and children of the minor steviol glycosides produced by extraction and enzymatic conversion of major steviol glycosides from stevia leaf. Several in vitro incubation tests were conducted in human fecal homogenates collected from adult and pediatric populations with steviol glycoside test samples comprised of a complex stevia leaf extract, a blend of minor glycosides isolated from stevia extract and two mixtures of steviol glycosides produced by enzymatic conversion of Reb A to larger molecules by attaching glucose units via ß- or α-glycosidic bonds. Results from these studies clearly demonstrate steviol glycosides produced by extraction from stevia leaf, or enzymatic conversion of stevia leaf extract, share the same metabolic fate in the human gut microbiota from adults and children. Considering a common metabolite structure and a shared metabolic fate in all ages, safety data for individual steviol glycosides can be used to support safety of all steviol glycosides produced by extraction and enzymatic conversion of stevia leaf extract.

In vitro metabolism of rebaudioside E under anaerobic conditions: Comparison with rebaudioside A.

The hydrolysis of the steviol glycosides rebaudioside (Reb) A and E, as well as steviolbioside (a metabolic intermediate) to steviol was evaluated in vitro using human fecal homogenates from healthy Caucasian and Asian donors. Incubation of each of the Rebs in both groups resulted in a rapid hydrolysis to steviol. Metabolism of 0.2mg/mL sample was complete within 24h, with the majority occurring within the first 16 h. There were no clear differences in the rate or extent of metabolism of Reb E relative to the comparative control Reb A. The hydrolysis of samples containing 2.0mg/mL of steviol glycosides Reb A and Reb E tended to take slightly longer than 0.2mg/mL samples. Herein, we report for the first time that there were no apparent gender or ethnicity differences in the rate of metabolism of any of the Rebs, regardless of the concentrations tested. Steviolbioside, an intermediate in the hydrolysis of Reb E to steviol was also found to be rapidly degraded to steviol. These results demonstrate Reb E is metabolized to steviol in the same manner as Reb A. These data support the use of toxicology data available on steviol, and on steviol glycosides metabolized to steviol (i.e., Reb A) to underpin the safety of Reb E.

In vitro metabolism of rebaudioside B, D, and M under anaerobic conditions: comparison with rebaudioside A.

The hydrolysis of the steviol glycosides rebaudioside A, B, D, and M, as well as of steviolbioside (a metabolic intermediate) to steviol was evaluated in vitro using human fecal homogenates from healthy donors under anaerobic conditions. Incubation of each of the rebaudiosides resulted in rapid hydrolysis to steviol. Metabolism was complete within 24h, with the majority occurring within the first 8h. There were no clear differences in the rate or extent of metabolism of rebaudioside B, D, or M, relative to the comparative control rebaudioside A. The hydrolysis of samples containing 2.0mg/mL of each rebaudioside tended to take slightly longer than solutions containing 0.2mg/mL. There was no apparent gender differences in the amount of metabolism of any of the rebaudiosides, regardless of the concentrations tested. An intermediate in the hydrolysis of rebaudioside M to steviol, steviolbioside, was also found to be rapidly degraded to steviol. The results demonstrate that rebaudiosides B, D, and M are metabolized to steviol in the same manner as rebaudioside A. These data support the use of toxicology data available on steviol, and on steviol glycosides metabolized to steviol (i.e., rebaudioside A) to substantiate the safety of rebaudiosides B, D, and M.

Specific correction of a splice defect in brain by nutritional supplementation.

Recent studies emphasize the importance of mRNA splicing in human genetic disease, as 20-30% of all disease-causing mutations are predicted to result in mRNA splicing defects. The plasticity of the mRNA splicing reaction has made these mutations attractive candidates for the development of therapeutics. Familial dysautonomia (FD) is a severe neurodegenerative disorder, and all patients have an intronic IVS20+6T>C splice site mutation in the IKBKAP gene, which results in tissue-specific skipping of exon 20 and a corresponding reduction in ikappaB kinase complex associated protein (IKAP) levels. We created transgenic mouse lines using a human IKBKAP bacterial artificial chromosome (BAC) into which we inserted the IKBKAP splice mutation (FD BAC) and have shown that the transgenic mice exhibit the same tissue-specific aberrant splicing patterns as seen in FD patients. We have previously demonstrated that the plant cytokinin kinetin can significantly improve the production of wild-type IKBKAP transcripts in FD lymphoblast cell lines by improving exon inclusion. In this study, we tested the ability of kinetin to alter IKBKAP splicing in the transgenic mice carrying the FD BAC and show that it corrects IKBKAP splicing in all major tissues assayed, including the brain. The amount of wild-type IKBKAP mRNA and IKAP protein was significantly higher in the kinetin-treated mice. These exciting results prove that treatment of FD, as well as other mechanistically related splicing disorders, with kinetin holds great promise as a potential therapeutic aimed at increasing normal protein levels, which may, in turn, slow disease progression.

Self-Reported Differences in Personality, Emotion Control, and Presence Between Pre-Military and Non-Military Groups in a Pilot Study Using the Stress Resilience in Virtual Environments (STRIVE) System.

Mental health disorders are the signature wounds of war resulting from extended U.S. Military conflicts in the Middle East [1]. In an effort to abate the number of Service Members that develop mental health disorders in these conflicts, USC-ICT has created the Stress Resilience in Virtual Environments (STRIVE) project, a set of highly realistic virtual reality combat scenarios and resilience-building sessions designed for pre-deployed military personnel. This short-paper looks at self-reported differences in personality, emotion control, and presence between two different groups, pre-military and non-military, of pilot subjects that tested a prototype of the first four modules of STRIVE.

Expansion of a VR Exposure Therapy System for Combat-Related PTSD to Medics/Corpsman and Persons Following Military Sexual Trauma.

The stressful experiences that have been characteristic of the combat environments in Iraq and Afghanistan have produced significant numbers of returning service members at risk for developing posttraumatic stress disorder and other psychosocial/behavioral health conditions. This paper describes a set of projects that are expanding the content for inclusion in a newly updated "Virtual Iraq/Afghanistan" Virtual Reality system for the delivery of exposure therapy (VRET) for PTSD with Service Members and Veterans. In addition to the complete rebuilding of this VRET system using the latest version of the Unity Game Engine, the system's content and functionality has been expanded to now support the use of VRET with combat medics/corpsmen and persons who have experienced military sexual trauma (MST). The focus of this paper is to present the rationale and general overview of the progress on these projects that will provide new relevant and customizable options for conducting VRET with a wider range of trauma experiences.

Who does well in life? Conscientious adults excel in both objective and subjective success.

This article investigates how personality and cognitive ability relate to measures of objective success (income and wealth) and subjective success (life satisfaction, positive affect, and lack of negative affect) in a representative sample of 9,646 American adults. In cross-sectional analyses controlling for demographic covariates, cognitive ability, and other Big Five traits, conscientiousness demonstrated beneficial associations of small-to-medium magnitude with all success outcomes. In contrast, other traits demonstrated stronger, but less consistently beneficial, relations with outcomes in the same models. For instance, emotional stability demonstrated medium-to-large associations with life satisfaction and affect but a weak association with income and no association with wealth. Likewise, extraversion demonstrated medium-to-large associations with positive affect and life satisfaction but small-to-medium associations with wealth and (lack of) negative affect and no association with income. Cognitive ability showed small-to-medium associations with income and wealth but no association with any aspect of subjective success. More agreeable adults were worse off in terms of objective success and life satisfaction, demonstrating small-to-medium inverse associations with those outcomes, but they did not differ from less agreeable adults in positive or negative affect. Likewise, openness to experience demonstrated small-to-medium inverse associations with every success outcome except positive affect, in which more open adults were slightly higher. Notably, in each of the five models predicting objective and subjective success outcomes, individual differences other than conscientiousness explained more variance than did conscientiousness. Thus, the benefits of conscientiousness may be remarkable more for their ubiquity than for their magnitude.