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Results of a phase Ib study of SB-121, an investigational probiotic formulation, a randomized controlled trial in participants with autism spectrum disorder.
Schmitt, LM, Smith, EG, Pedapati, EV, Horn, PS, Will, M, Lamy, M, Barber, L, Trebley, J, Meyer, K, Heiman, M, et al
Scientific reports. 2023;(1):5192
Abstract
Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by core impairments in social communication as well as restricted, repetitive patterns of behavior and/or interests. Individuals with ASD, which includes about 2% of the US population, have challenges with activities of daily living and suffer from comorbid medical and mental health concerns. There are no drugs indicated for the core impairments of ASD. As such, there is a significant need for the development of new medication strategies for individuals with ASD. This first-in-human placebo-controlled, double-blind, crossover study investigated the safety (primary objective) and efficacy of oral SB-121, a combination of L. reuteri, Sephadex® (dextran microparticles), and maltose administered once daily for 28 days in 15 autistic participants. SB-121 was safe and well tolerated. SB-121-associated directional improvements in adaptive behavior measured by Vineland-3 and social preference as measured with eye tracking were noted. These results provide support for further clinical evaluation of SB-121 as a treatment in autistic patients. To evaluate the safety and tolerability of multiple doses of SB-121 in subjects with autism spectrum disorder. Single-center, randomized, placebo-controlled, double-blind, crossover trial. 15 patients with autism spectrum disorder were randomized and analyzed. Daily dosing of SB-121 or placebo for 28 days, followed by approximately a 14 day washout, then 28 days of dosing with other treatment. Incidence and severity of adverse events, presence of Limosilactobacillus reuteri and Sephadex® in stool, and incidence of bacteremia with positive L. reuteri identification. Additional outcomes include changes from baseline on cognitive and behavior tests as well as biomarker levels. Adverse event rates were similar between SB-121 and placebo, with most reported as mild. There were no severe or serious adverse events. No participants had features of suspected bacteremia or notable changes in vital signs, safety laboratory, or ECG parameters from baseline. There was a statistically significant increase from baseline in the Vineland-3 Adaptive Behavior Composite score (p = 0.03) during SB-121 treatment. There was a trend for increased social/geometric viewing ratio following SB-121 treatment compared to placebo. SB-121 was safe and well tolerated. SB-121-associated directional improvements in adaptive behavior measured by Vineland-3 and social preference as measured with eye tracking were noted.Trial registration: clinicaltrials.gov Identifier: NCT04944901.
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Gastrointestinal microbiome modulator improves glucose tolerance in overweight and obese subjects: A randomized controlled pilot trial.
Rebello, CJ, Burton, J, Heiman, M, Greenway, FL
Journal of diabetes and its complications. 2015;(8):1272-6
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Abstract
OBJECTIVE The objective of this study was to examine the effects of a gastrointestinal microbiome modulator (GIMM) containing inulin, β-glucan, blueberry anthocyanins, and blueberry polyphenols on metabolic parameters, fecal markers of gut microbiota, and satiety. DESIGN AND METHODS Thirty overweight or obese individuals aged 18 to 70years, were enrolled in a randomized controlled trial. Participants consumed the test product or placebo daily for four weeks. Stool samples were collected and blood was drawn at baseline and week four for assessments of gut microbiota, satiety hormones, glucose control, and lipid measures. Subjective satiety was assessed weekly. Linear models were used to compare differences from baseline to week four. RESULTS GIMM consumption improved blood glucose tolerance (p=0.008), and increased satiety (p=0.03). There were no statistically significant differences in insulin sensitivity, fecal markers of gut microbiota, plasma satiety hormones, or serum lipid concentrations between the groups. However, plasma satiety hormones and fecal short chain fatty acid concentrations increased in the test group compared to the placebo. CONCLUSIONS GIMM consumption for four weeks, increases satiety, and improves glucose tolerance possibly through insulin-independent pathways.
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Dietary fructose reduces circulating insulin and leptin, attenuates postprandial suppression of ghrelin, and increases triglycerides in women.
Teff, KL, Elliott, SS, Tschöp, M, Kieffer, TJ, Rader, D, Heiman, M, Townsend, RR, Keim, NL, D'Alessio, D, Havel, PJ
The Journal of clinical endocrinology and metabolism. 2004;(6):2963-72
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Abstract
Previous studies indicate that leptin secretion is regulated by insulin-mediated glucose metabolism. Because fructose, unlike glucose, does not stimulate insulin secretion, we hypothesized that meals high in fructose would result in lower leptin concentrations than meals containing the same amount of glucose. Blood samples were collected every 30-60 min for 24 h from 12 normal-weight women on 2 randomized days during which the subjects consumed three meals containing 55, 30, and 15% of total kilocalories as carbohydrate, fat, and protein, respectively, with 30% of kilocalories as either a fructose-sweetened [high fructose (HFr)] or glucose-sweetened [high glucose (HGl)] beverage. Meals were isocaloric in the two treatments. Postprandial glycemic excursions were reduced by 66 +/- 12%, and insulin responses were 65 +/- 5% lower (both P < 0.001) during HFr consumption. The area under the curve for leptin during the first 12 h (-33 +/- 7%; P < 0.005), the entire 24 h (-21 +/- 8%; P < 0.02), and the diurnal amplitude (peak - nadir) (24 +/- 6%; P < 0.0025) were reduced on the HFr day compared with the HGl day. In addition, circulating levels of the orexigenic gastroenteric hormone, ghrelin, were suppressed by approximately 30% 1-2 h after ingestion of each HGl meal (P < 0.01), but postprandial suppression of ghrelin was significantly less pronounced after HFr meals (P < 0.05 vs. HGl). Consumption of HFr meals produced a rapid and prolonged elevation of plasma triglycerides compared with the HGl day (P < 0.005). Because insulin and leptin, and possibly ghrelin, function as key signals to the central nervous system in the long-term regulation of energy balance, decreases of circulating insulin and leptin and increased ghrelin concentrations, as demonstrated in this study, could lead to increased caloric intake and ultimately contribute to weight gain and obesity during chronic consumption of diets high in fructose.