Raylene A. Reimer

Low-Dose Aspartame Consumption Differentially Affects Gut Microbiota-Host Metabolic Interactions in the Diet-Induced Obese Rat

Aspartame consumption is implicated in the development of obesity and metabolic disease despite the intention of limiting caloric intake. The mechanisms responsible for this association remain unclear, but may involve circulating metabolites and the gut microbiota. Aims were to examine the impact of chronic low-dose aspartame consumption on anthropometric, metabolic and microbial parameters in a diet-induced obese model. Male Sprague-Dawley rats were randomized into a standard chow diet (CH, 12% kcal fat) or high fat (HF, 60% kcal fat) and further into ad libitum water control (W) or low-dose aspartame (A, 5–7 mg/kg/d in drinking water) treatments for 8 week (n = 10–12 animals/treatment). Animals on aspartame consumed fewer calories, gained less weight and had a more favorable body composition when challenged with HF compared to animals consuming water. Despite this, aspartame elevated fasting glucose levels and an insulin tolerance test showed aspartame to impair insulin-stimulated glucose disposal in both CH and HF, independently of body composition. Fecal analysis of gut bacterial composition showed aspartame to increase total bacteria, the abundance of Enterobacteriaceae and Clostridium leptum. An interaction between HF and aspartame was also observed for Roseburia ssp wherein HF-A was higher than HF-W (P<0.05). Within HF, aspartame attenuated the typical HF-induced increase in the Firmicutes:Bacteroidetes ratio. Serum metabolomics analysis revealed aspartame to be rapidly metabolized and to be associated with elevations in the short chain fatty acid propionate, a bacterial end product and highly gluconeogenic substrate, potentially explaining its negative affects on insulin tolerance. How aspartame influences gut microbial composition and the implications of these changes on the development of metabolic disease require further investigation.

Dietary supplementation of high-performance Canadian athletes by age and gender.

Objective:To determine dietary supplementation practices and opinions, preferred means for dietary supplement (DS) education, and antidoping opinions among elite Canadian athletes varying in age and gender. Design:A descriptive, cross-sectional survey. Setting:Elite athlete training centers in Calgary, Canada and surrounding area. Participants:A total of 582 high-performance athletes (314 male, 268 female). Main Outcome Measures:High-performance athletes representing 27 sports with a mean age of 19.96 ± 3.91 years completed a validated questionnaire assessing DS practices and opinions by recall. Sport categories included varsity, Canadian Sport Centre Calgary (CSCC), and National Sport School (NSS). Results:There was extensive DS use, with 88.4% of participants taking ≥1 DS (mean of 3.08 ± 1.87 DS per user) during the previous 6 months. Overall, sport drinks (22.4%), sport bars (14.0%), multivitamins and minerals (13.5%), protein supplements (9.0%), and vitamin C (6.4%) were most frequently reported. Older athletes were significantly more likely to report greater DS usage; to be advised by teammates, health food store retailers, and magazines; to prefer supplementation education via individual interviews; to claim awareness of anti-doping rules; and to perceive anti-doping compliance. Relative to gender, significant differences were observed for the types of DS reported; supplementation advisors; justifications for DS use; and awareness of anti-doping regulations. Conclusions:Utilization of this validated and reliable questionnaire has the potential for broad use and provides insight into the factors that influence DS use in elite athletes.

Combined effects of oligofructose and Bifidobacterium animalis on gut microbiota and glycemia in obese rats

Prebiotics and probiotics may be able to modify an obesity‐associated gut microbiota. The aim of this study was to examine the individual and combined effects of the prebiotic oligofructose (OFS) and the probiotic Bifidobacterium animalis subsp. lactis BB‐12 (BB‐12) on gut microbiota and host metabolism in obese rats.

The potential role of prebiotic fibre for treatment and management of non-alcoholic fatty liver disease and associated obesity and insulin resistance.

Non‐alcoholic fatty liver disease (NAFLD) and the more severe non‐alcoholic steatohepatitis (NASH) represent a spectrum of diseases involving hepatic fat accumulation and histological features essentially identical to alcoholic liver disease; however, they occur in the absence of excessive alcohol intake. They typically arise in conjunction with one or more features of the metabolic syndrome. Lifestyle mediated weight loss remains the primary mode of therapy for NAFLD and NASH, but this is often ineffective and adjunctive medical and surgical treatments are presently lacking. Prebiotic fibres are a group of non‐digestible carbohydrates that modulate the human microbiota in a manner that is advantageous to host health. Rodent studies suggest that dietary supplementation with prebiotic fibres positively impacts NAFLD by modifying the gut microbiota, reducing body fat, and improving glucoregulation. Future research should focus on placebo‐controlled, human, clinical trials using histological endpoints to address the effects of prebiotics on NAFLD and NASH. The aim of this review is to summarize current knowledge about prebiotics as an emerging therapeutic target for NAFLD.

Effect of prebiotic fibre supplementation on hepatic gene expression and serum lipids: a dose-response study in JCR:LA-cp rats.

Prebiotic fibres have been proposed to promote weight loss and lower serum cholesterol; however, the mechanisms are not fully understood. The aim of the present research was to identify possible mechanisms through which prebiotic fibres improve serum lipids. Lean and obese JCR:La-cp rats aged 8 weeks consumed one of three diets supplemented with 0, 10 or 20 % prebiotic fibre for 10 weeks. Rats were anaesthetised and a fasting blood sample was taken for lipid analysis. Real-time PCR was used to determine gene expression for cholesterol and fatty acid regulatory genes in liver tissue. Liver and caecal digesta cholesterol and TAG content were quantified. Both doses of prebiotic fibre lowered serum cholesterol levels by 24 % in the obese hyperlipidaemic rats (P < 0.05). This change was associated with an increase in caecal digesta as well as an up-regulation of genes involved in cholesterol synthesis and bile production. Additionally, there was a 42 % reduction in TAG accumulation in the liver of the obese rats with 10 % prebiotic diet (P < 0.05); however, no change in liver fatty acid synthase (FAS). Prebiotic fibres appear to lower cholesterol levels through increased cholesterol excretion in the form of bile and inhibit the accumulation of TAG in the liver through a mechanism unrelated to FAS. These effects appear to be limited to the obese model and particularly the 10 % dose. The present work is significant as it provides insight into the mechanisms of action for prebiotic fibres on lipid metabolism and furthers the development of dietary treatments for hypercholesterolaemia.

Prebiotic fiber modulation of the gut microbiota improves risk factors for obesity and the metabolic syndrome.

Prebiotic fibers are non-digestible carbohydrates that promote the growth of beneficial bacteria in the gut. Prebiotic consumption may benefit obesity and associated co-morbidities by improving or normalizing the dysbiosis of the gut microbiota. We evaluated the dose response to a prebiotic diet on the gut microbiota, body composition and obesity associated risk factors in lean and genetically obese rats. Prebiotic fibers increased Firmicutes and decreased Bacteroidetes, a profile often associated with a leaner phenotype. Bifidobacteria and Lactobacillus numbers also increased. Changes in the gut microbiota correlated with energy intake, glucose, insulin, satiety hormones, and hepatic cholesterol and triglyceride accumulation. Here we provide a comprehensive analysis evaluating the results through the lens of the gut microbiota. Salient, new developments impacting the interpretation and significance of our data are discussed. We propose that prebiotic fibers have promise as a safe and cost-effective means of modulating the gut microbiota to promote improved host:bacterial interactions in obesity and insulin resistance. Human clinical trials should be undertaken to confirm these effects.Prebiotic fibers are non-digestible carbohydrates that promote the growth of beneficial bacteria in the gut. Prebiotic consumption may benefit obesity and associated co-morbidities by improving or normalizing the dysbiosis of the gut microbiota. We evaluated the dose response to a prebiotic diet on the gut microbiota, body composition and obesity associated risk factors in lean and genetically obese rats. Prebiotic fibers increased Firmicutes and decreased Bacteroidetes, a profile often associated with a leaner phenotype. Bifidobacteria and Lactobacillus numbers also increased. Changes in the gut microbiota correlated with energy intake, glucose, insulin, satiety hormones, and hepatic cholesterol and triglyceride accumulation. Here we provide a comprehensive analysis evaluating the results through the lens of the gut microbiota. Salient, new developments impacting the interpretation and significance of our data are discussed. We propose that prebiotic fibers have promise as a safe and cost-effective means of modulating the gut microbiota to promote improved host:bacterial interactions in obesity and insulin resistance. Human clinical trials should be undertaken to confirm these effects.

Glucose tolerance, lipids, and GLP-1 secretion in JCR:LA-cp rats fed a high protein fiber diet.

Background: We have shown that individually, dietary fiber and protein increase secretion of the anorexigenic and insulinotropic hormone, glucagon‐like peptide‐1 (GLP‐1).

Prebiotic Fiber Increases Hepatic Acetyl CoA Carboxylase Phosphorylation and Suppresses Glucose-Dependent Insulinotropic Polypeptide Secretion More Effectively When Used with Metformin in Obese Rats

Independently, metformin (MET) and the prebiotic, oligofructose (OFS), have been shown to increase glucagon-like peptide (GLP-1) secretion. Our objective was to determine whether using OFS as an adjunct with MET augments GLP-1 secretion in obese rats. Male, diet-induced obese Sprague Dawley rats were randomized to: 1) high-fat/-sucrose diet [HFHS; control (C); 20% fat, 50% sucrose wt:wt]; 2) HFHS+10% OFS (OFS); 3) HFHS + MET [300 mg/kg/d (MET)]; 4) HFHS+10% OFS+MET (OFS+MET). Body composition, glycemia, satiety hormones, and mechanisms related to dipeptidyl peptidase 4 (DPP4) activity in plasma, hepatic AMP-activated protein kinase (AMPK; Western blots), and gut microbiota (qPCR) were examined. Direct effects of MET and SCFA were examined in human enteroendocrine cells. The interaction between OFS and MET affected fat mass, hepatic TG, secretion of glucose-dependent insulinotropic polypeptide (GIP) and leptin, and AMPKα2 mRNA and phosphorylated acetyl CoA carboxylase (pACC) levels (P < 0.05). Combined, OFS and MET reduced GIP secretion to a greater extent than either treatment alone (P < 0.05). The hepatic pACC level was increased by OFS+MET by at least 50% above all other treatments, which did not differ from each other (P < 0.05). OFS decreased plasma DPP4 activity (P < 0.001). Cecal Bifidobacteria (P < 0.001) were markedly increased and C. leptum decreased (P < 0.001) with OFS consumption. In human enteroendocrine cells, the interaction between MET and SCFA affected GLP-1 secretion (P < 0.04) but was not associated with higher GLP-1 than the highest individual doses. In conclusion, the combined actions of OFS and MET were associated with important interaction effects that have the potential to improve metabolic outcomes associated with obesity.

Changes in satiety hormones and expression of genes involved in glucose and lipid metabolism in rats weaned onto diets high in fibre or protein reflect susceptibility to increased fat mass in adulthood

Risk of developing obesity and diabetes may be influenced by the nutritional environment early in life. We examined the effects of high fibre or protein diets on satiety hormones and genes involved in glucose and lipid metabolism during postnatal development and on adult fat mass. At 21 days of age, Wistar rat pups were weaned onto control (C), high fibre (HF) or high protein (HP) diet. Tissue and blood were collected at 7, 14, 21, 28 and 35 days after birth. A second group of rats consumed the weaning diets until 4 months when they were switched to a high fat–high sugar diet for 6 weeks, after which body and fat mass and plasma glucose were determined. In young rats, HF diet increased plasma glucagon‐like peptide (GLP‐1) compared to C and HP and decreased leptin compared to C at postnatal days 28 and 35. Hepatic fatty acid synthase mRNA was down‐regulated by HF and HP compared to C at days 28 and 35. In brown adipose tissue, HF increased uncoupling protein‐3 mRNA whereas HP increased mRNA of the inflammatory cytokine interleukin‐6. Body weight, fat mass and glycaemia in adult males and fat mass in females were greater after the high fat challenge in rats that consumed the HP diet from weaning. Increasing fibre or protein in postnatal diets causes rapid change in satiety hormone secretion and genes involved in glucose and lipid metabolism which appear to influence fat mass and glycaemia in adulthood, high protein being associated with increased susceptibility to obesity.

Chronic coffee consumption in the diet-induced obese rat: impact on gut microbiota and serum metabolomics.

Epidemiological data confirms a strong negative association between regular coffee consumption and the prevalence of type 2 diabetes. Coffee is initially absorbed in the stomach and small intestine but is further fermented in the colon by gut microbiota. The bioavailability, production and biological activity of coffee polyphenols is modulated, in part, by gut microbiota. The purpose of this study was to determine if chronic coffee consumption could mitigate negative gut microbiota and metabolomic profile changes induced by a high-fat diet. Male Sprague-Dawley rats were randomized to chow (12% kcal fat) or high-fat (60% kcal fat) diet. Each group was further divided into water or caffeinated coffee for 10 weeks. Coffee consumption in high-fat-fed rats was associated with decreased body weight, adiposity, liver triglycerides and energy intake. Despite a more favorable body composition, rats displayed profound systemic insulin resistance, likely due to caffeine. Coffee consumption attenuated the increase in Firmicutes (F)-to-Bacteroidetes (B) ratio and Clostridium Cluster XI normally associated with high-fat feeding but also resulted in augmented levels of Enterobacteria. In the serum metabolome, coffee had a distinct impact, increasing levels of aromatic and circulating short-chain fatty acids while lowering levels of branched-chain amino acids. In summary, coffee consumption is able to alter gut microbiota in high-fat-fed rats although the role of these changes in reducing diabetes risk is unclear given the increased insulin resistance observed with coffee in this study.