Inclusion of Oat Polar Lipids in a Solid Breakfast Improves Glucose Tolerance, Triglyceridemia, and Gut Hormone Responses Postprandially and after a Standardized Second Meal: A Randomized Crossover Study in Healthy Subjects.

Previously, it has been indicated that oat polar lipids included in a liquid meal may have the potential to beneficially modulate various cardiometabolic variables. The purpose of this study was to evaluate the effects of oat polar lipids in a solid food matrix on acute and second meal glucose tolerance, blood lipids, and concentrations of gut-derived hormones. The oat polar lipids were consumed at breakfast and effects on the biomarkers were investigated in the postprandial period and following a standardized lunch. Twenty young, healthy subjects consumed in total four different breakfast meals in a crossover study design. The breakfasts consisted of 1. White wheat bread (WWB) with an added 7.5 g of oat polar lipids (PLL); 2. WWB with an added 15 g of oat polar lipids (PLH); 3. WWB with and added 16.6 g of rapeseed oil (RSO) as a representative of commonly consumed oils; and 4. WWB consumed alone, included as a reference. All products with added lipids contained equivalent amounts of fat (16.6 g) and available carbohydrates (50 g). Rapeseed oil was added to the oat polar lipid meals to equal 16.6 g of total fat. The standardized lunch was composed of WWB and meatballs and was served 3.5 h after the breakfast. Test variables (blood glucose, serum insulin, triglyceride (TG), free fatty acids (FFA), ghrelin, GLP-1, PYY, and GIP) were measured at fasting and repeatedly during the 5.5 h after ingestion of the breakfast. After breakfast, PLH substantially lowered postprandial glucose and insulin responses (iAUC 0-120 min) compared with RSO and WWB (p < 0.05). Furthermore, a reduced glycaemic response to lunch (210-330 min) was observed following the PLH breakfast compared to all of the other breakfasts served (p < 0.05). Oat polar lipids (PLH) significantly reduced TG and ghrelin and increased circulating gut hormones GLP-1 and PYY compared to RSO (p < 0.05). The results show that exchanging part of the dietary lipids with oat polar lipids has the potential to improve postprandial blood glucose regulation and gut hormones and thus may have a preventive effect against type 2 diabetes.

Critical review on anti-obesity effects of phytochemicals through Wnt/ß-catenin signaling pathway.

Phytochemicals have been used as one of the sources for the development of anti-obesity drugs. Plants are rich in a variety of bioactive compounds including polyphenols, saponins and terpenes. Phytochemicals inhibit adipocyte differentiation by inhibiting the transcription and translation of adipogenesis transcription factors such as C/EBPα and PPARγ. It has been proved that phytochemicals inhibit the genes and proteins associated with adipogenesis and lipid accumulation by activating Wnt/ß-catenin signaling pathway. The activation of Wnt/ß-catenin signaling pathway by phytochemicals is multi-target regulation, including the regulation of pathway critical factor ß-catenin and its target gene, the downregulation of destruction complex, and the up-regulation of Wnt ligands, its cell surface receptor and Wnt antagonist. In this review, the literature on the anti-obesity effect of phytochemicals through Wnt/ß-catenin signaling pathway is collected from Google Scholar, Scopus, PubMed, and Web of Science, and summarizes the regulation mechanism of phytochemicals in this pathway. As one of the alternative methods of weight loss drugs, Phytochemicals inhibit adipogenesis through Wnt/ß-catenin signaling pathway. More progress in relevant fields may pose phytochemicals as the main source of anti-obesity treatment.

Evaluation of hypoglycemic effect, safety and immunomodulation of Prevotella copri in mice.

The gut bacterium Prevotella copri (P. copri) has been shown to lower blood glucose levels in mice as well as in healthy humans, and is a promising candidate for a next generation probiotic aiming at prevention or treatment of obesity and type 2 diabetes. In this study the hypoglycemic effect of live P. copri was confirmed in mice and pasteurization of P. copri was shown to further enhance its capacity to improve glucose tolerance. The safety of live and pasteurized P. copri was evaluated by a 29-day oral toxicity study in mice. P. copri did not induce any adverse effects on body growth. General examination of the mice, gross pathological and histological analysis showed no abnormalities of the vital organs. Though relative liver weights were lower in the pasteurized (4.574 g ± 0.096) and live (4.347 g ± 0.197) P. copri fed groups than in the control mice (5.005 g ± 0.103) (p = 0.0441 and p = 0.0147 respectively), no liver biochemical marker aberrations were detected. Creatinine serum levels were significantly lower in mice fed with live (p = 0.001) but not pasteurized (p = 0.163) P. copri compared to those of control mice. Haematological parameter analysis and low plasma Lipopolysaccharide Binding Protein (LBP) levels ruled out systemic infection and inflammation. Immunomodulation capacity by P. copri as determined by blood plasma cytokine analysis was limited and gut colonisation occurred in only one of the 10 mice tested. Taken together, no major adverse effects were detected in P. copri treated groups compared to controls.

Oat Polar Lipids Improve Cardiometabolic-Related Markers after Breakfast and a Subsequent Standardized Lunch: A Randomized Crossover Study in Healthy Young Adults.

It has been suggested that intake of polar lipids may beneficially modulate various metabolic variables. The purpose of this study was to evaluate the effect of oat polar lipids on postprandial and second meal glycemic regulation, blood lipids, gastrointestinal hormones, and subjective appetite-related variables in healthy humans. In a randomized design, twenty healthy subjects ingested four liquid cereal-based test beverages (42 g of available carbohydrates) containing: i. 30 g of oat oil with a low concentration (4%) of polar lipids (PLL), ii. 30 g of oat oil containing a high concentration (40%) of polar lipids (PLH), iii. 30 g of rapeseed oil (RSO), and iv. no added lipids (NL). The products were served as breakfast meals followed by a standardized lunch. Test variables were measured at fasting and during 3 h after breakfast and two additional hours following a standardized lunch. PLH reduced glucose and insulin responses after breakfast (0-120 min) compared to RSO, and after lunch (210-330 min) compared to RSO and PLL (p < 0.05). Compared to RSO, PLH resulted in increased concentrations of the gut hormones GLP-1 and PYY after the standardized lunch (p < 0.05). The results suggest that oat polar lipids have potential nutraceutical properties by modulating acute and second meal postprandial metabolic responses.

Development of a real-time quantitative PCR method for detection and quantification of Prevotella copri.

BACKGROUND: Since its discovery in 2007, the importance of the human gut bacterium Prevotella copri (P. copri) has been widely recognized with its links to diet and health status and potential as next generation probiotic. Therefore, precise, convenient and cost-effective diagnostic tools for the detection and quantification of P. copri from clinical and environmental samples are needed. RESULTS: In this study, a Sybr Green qPCR protocol for P. copri detection and quantification was developed and tested on P. copri-spiked murine faeces samples targeting both the 16S rRNA gene and P. copri genome specific genes. The use of one 16S rRNA primer pair and 2 genome specific primer pairs resulted in at least 10x higher specificity and sensitivity than the primer-only PCR currently cited in the literature, reaching a sensitivity of 103 CFU/mL. Furthermore, we showed that the new 16S rRNA primer set provided the best balance of detection of a wide range of P. copri strains, while avoiding off-target detection of other Prevotella genus species. The quantification of P. copri in human stool samples using the new 16S rRNA primers also correlated well with 16S rRNA high throughput MiSeq sequencing data (r2 = 0.6604, p = 0.0074). The two genome specific primer pairs on the other hand uniquely detect the DSM18205 reference strain, allowing differential detection of indigenous and experimentally administered P. copri populations. Finally, it was shown that SYBR green qPCR mixes have an influence on sensitivity and specificity, with Biorad SsoAdvanced Universal SYBR Green Supermix performing the best under our test conditions of six commercially available SYBR green master mixes. CONCLUSIONS: This improved qPCR-based method will allow accurate P. copri identification and quantification. Moreover, this methodology can also be applied to identify other bacterial species in complex samples.

Interacting With a Visiting Dog Increases Fingertip Temperature in Elderly Residents of Nursing Homes.

The aim of this study was to investigate whether interacting with a visiting dog influences fingertip temperature and cortisol levels in residents living in nursing homes for the elderly. The study included two groups, the dog group (n = 13) and the control group (n = 11-15) and lasted for 8 weeks for the dog group and 6 weeks for the control group. All participants were residents living at nursing homes for the elderly. The researchers visited small groups of the participants twice weekly during the entire study in both the dog and the control group. The visiting dog and the dog handler accompanied the researchers during weeks 3-6. Fingertip temperature was measured and saliva samples for cortisol determination were collected at 0, 20 and 60 min for the dog group and at 0 and 20 min for the control group. For analysis the study was divided into periods; Period 1 (week 1-2), Period 2 (week 3-4), Period 3 (week 5-6) and Period 4 (week 7-8, only the dog group). Mean values based on all data obtained at 0 and 20 min during period 1-3 were compared between groups. A second, separate analysis for the dog group also included data from 60 min and for period 4. For the dog group fingertip temperature increased significantly between period 1 and 2, 1 and 3 and 1 and 4 (p < 0.05). In addition, fingertip temperature rose significantly between 0 and 20 min and between 0 and 60 min within all periods. For the control group a significant decrease in fingertip temperature was observed between period 1 and 3 (p < 0.05). Fingertip temperature did not differ between the two groups during period 1, but was significantly higher for the dog group than for the control group during periods 2 and 3 (p < 0.05 and p < 0.001, respectively). Cortisol results are only presented descriptively due to that many samples had too low volume of saliva to be analyzed. In the present study interaction between elderly residents and a visiting dog resulted in increased fingertip temperature, probably reflecting a decrease in the activity of the sympathetic nervous system and therefore a decrease in stress levels.

Taxogenomic assessment and genomic characterisation of Weissella cibaria strain 92 able to metabolise oligosaccharides derived from dietary fibres.

The importance of the gut microbiota in human health has led to an increased interest to study probiotic bacteria. Fermented food is a source of already established probiotics, but it also offers an opportunity to discover new taxa. Four strains of Weissella sp. isolated from Indian fermented food have been genome sequenced and classified into the species W. cibaria based on whole-genome phylogeny. The genome of W. cibaria strain 92, known to utilise xylooligosaccharides and produce lactate and acetate, was analysed to identify genes for oligosaccharide utilisation. Clusters including genes involved in transportation, hydrolysis and metabolism of xylooligosaccharides, arabinooligosaccharides and ß-glucosides were identified. Growth on arabinobiose and laminaribiose was detected. A 6-phospho-ß-glucosidase clustered with a phosphotransferase system was found upregulated during growth on laminaribiose, indicating a mechanism for laminaribiose utilisation. The genome of W. cibaria strain 92 harbours genes for utilising the phosphoketolase pathway for the production of both acetate and lactate from pentose and hexose sugars but lacks two genes necessary for utilising the pentose phosphate pathway. The ability of W. cibaria strain 92 to utilise several types of oligosaccharides derived from dietary fibres, and produce lactate and acetate makes it interesting as a probiotic candidate for further evaluation.

Abundance of gut Prevotella at baseline and metabolic response to barley prebiotics.

PURPOSE: We previously showed that short-term intervention with barley kernel bread (BKB) improved glucose tolerance. However, glucose tolerance was not improved in a subset of individuals (non-responders) who were characterized by a low Prevotella/Bacteroides ratio. The purpose of the present study was to investigate if the baseline Prevotella/Bacteroides ratio can be used to stratify metabolic responders and non-responders to barley dietary fiber (DF). METHODS: Fecal samples were collected from 99 healthy humans with BMI < 28 kg/m2 between 50 and 70 years old. The abundance of fecal Prevotella and Bacteroides was quantified with 16S rRNA quantitative PCR. 33 subjects were grouped in three groups: subjects with highest Prevotella/Bacteroides ratios, "HP", n = 12; subjects with lowest Prevotella/Bacteroides ratios, "LP", n = 13; and subjects with high abundance of both measured bacteria, HPB, n = 8. A 3-day randomized crossover intervention with BKB and white wheat bread (control) was performed. Cardiometabolic test variables were analyzed the next day following a standardized breakfast. RESULTS: The BKB intervention lowered the blood glucose responses to the breakfast independently of Prevotella/Bacteroides ratios (P < 0.01). However, independently of intervention, the HP group displayed an overall lower insulin response and lower IL-6 concentrations compared with the LP group (P < 0.05). Furthermore, the groups HP and HPB showed lower hunger sensations compared to the LP group (P < 0.05). CONCLUSIONS: Here we show that the abundance of gut Prevotella and Bacteroides at baseline did not stratify metabolic responders and non-responders to barley DF intervention. However, our results indicate the importance of gut microbiota in host metabolic regulation, further suggesting that higher Prevotella/Bacteroides ratio may be favorable. CLINICALTRIALS. GOV ID: NCT02427555.

Impact of rye-based evening meals on cognitive functions, mood and cardiometabolic risk factors: a randomized controlled study in healthy middle-aged subjects.

BACKGROUND: Whole grain (WG) intake is associated with reduced risk of obesity, type 2 diabetes and cardiovascular disease, whereas type 2 diabetes increases the risk of cognitive decline and dementia. The purpose of this study was to investigate the effects of short-term intervention with WG rye on cognitive functions, mood and cardiometabolic risk markers in middle-aged test subjects. METHOD: Rye-based breads were provided to 38 healthy test subjects (aged 52-70y) during three consecutive days in a crossover study design, using white wheat flour bread (WWB) as a reference. The rye-based bread consisted of a WG rye kernel/flour mixture (1:1 ratio) supplemented with resistant starch type 2 (RS2) (RB + RS2). The last bread portion was ingested at 2100 h, and cognitive function, mood and cardiometabolic risk markers were determined the following morning, 11 - 14 h post intake. RESULTS: In comparison to WWB, the RB + RS2 product increased ratings of mood parameters (valance, P < 0.001; activation P < 0.05). No differences were seen in the cognitive tests depending on intervention (P > 0.05). RB + RS2 increased insulin sensitivity (P < 0.05), fasting levels of gut hormones (PYY, P < 0.05; GLP-2, P < 0.01) and fasting concentrations of plasma acetate, butyrate and total SCFA (P < 0.001). In contrast, fasting levels of IL - 1ß were decreased (P < 0.05). Insulin sensitivity was positively correlated with working memory test performance (P < 0.05). CONCLUSIONS: This study display novel findings regarding effects of WG rye products on mood, and glucose and appetite regulation in middle-aged subjects, indicating anti-diabetic properties of WG rye. The beneficial effects are suggested to be mediated through gut fermentation of dietary fiber in the RB + RS2 product. TRIAL REGISTRATION: The study was retrospectively registered at ClinicalTrials.gov, register number NCT03275948 . Registered September 8 2017.

Increased Plasma Brain-Derived Neurotrophic Factor 10.5 h after Intake of Whole Grain Rye-Based Products in Healthy Subjects.

It has previously been shown in short-term interventions that kernel-based whole grain (WG) rye products have beneficial effects on test markers related to obesity and type 2 diabetes (T2D). T2D increases the risk of several severe health issues, including declined cognitive functions. The protein brain-derived neurotrophic factor (BDNF) is suggested to be a potential biomarker for neuronal integrity. The aim of this study was to investigate the effect on plasma BDNF concentrations, 10.5 h after the intake of WG rye. Healthy young adults were provided late evening meals consisting of WG rye kernel-based bread (RKB) or a white wheat flour-based bread (reference product (WWB)), in a randomized cross-over design. The BDNF concentrations were investigated at fasting in the morning 10.5 h after single evening meals with RKB and WWB, and also after three consecutive evening meals with RKB and WWB, respectively. No difference was observed in the BDNF concentrations depending on the priming setting (p > 0.05). The RKB evening meals increased the BDNF concentrations by 27% at fasting (p = 0.001), compared to WWB. The increase of BDNF after the RKB indicate that, in addition to anti-diabetic properties, the dietary fiber in WG rye may support neuronal integrity.

Impact of Rye Kernel-Based Evening Meal on Microbiota Composition of Young Healthy Lean Volunteers With an Emphasis on Their Hormonal and Appetite Regulations, and Blood Levels of Brain-Derived Neurotrophic Factor.

Rye kernel bread (RKB) evening meals improve glucose tolerance, enhance appetite regulation and increase satiety in healthy volunteers. These beneficial effects on metabolic responses have been shown to be associated with increased gut fermentation. The present study aimed to elucidate if RKB evening meals may cause rapid alterations in microbiota composition that might be linked to metabolic-, immune-, and appetite- parameters. Gut-brain axis interaction was also studied by relating microbiota composition to amount of brain-derived neurotrophic factor (BDNF) in blood plasma. Nineteen healthy volunteers, ten women and nine men aged 22-29 years, BMI < 25 (NCT02093481) participated in the study performed in a crossover design. Each person was assigned to either white wheat bread (WWB) or RKB intake as a single evening meal or three consecutive evenings. Stool and blood samples as well as subjective appetite ratings were obtained the subsequent morning after each test occasion, resulting in four independent collections per participant (n = 76). DNA was extracted from the fecal samples and V4 hypervariable region of the bacterial 16S rRNA genes was sequenced using next generation sequencing technology. Higher abundance of Prevotella and Faecalibacterium with simultaneous reduction of Bacteroides spp. were observed after RKB meals compared to WWB. The associations between metabolic test variables and microbiota composition showed a positive correlation between Bacteroides and adiponectin levels, whereas only Prevotella genus was found to have positive association with plasma levels of BDNF. These novel findings in gut-brain interactions might be of importance, since decreased levels of BDNF, that plays an essential role in brain function, contribute to the pathogenesis of several major neurodisorders, including Alzheimer's. Thus, daily consumption of Faecalibacterium- and/or Prevotella-favoring meals should be investigated further for their potential to prevent neurodegenerative processes in the brain.

Effects of a mixed berry beverage on cognitive functions and cardiometabolic risk markers; A randomized cross-over study in healthy older adults.

BACKGROUND: Berries and associated bioactive compounds, e.g. polyphenols and dietary fibre (DF), may have beneficial implications with respect to the metabolic syndrome, including also cognitive functions. The aim of this study was to evaluate effects on cognitive functions and cardiometabolic risk markers of 5 wk intervention with a mixture of berries, in healthy humans. METHODS: Forty healthy subjects between 50-70 years old were provided a berry beverage based on a mixture of berries (150g blueberries, 50g blackcurrant, 50g elderberry, 50g lingonberries, 50g strawberry, and 100g tomatoes) or a control beverage, daily during 5 weeks in a randomized crossover design. The control beverage (water based) was matched with respect to monosaccharides, pH, and volume. Cognitive tests included tests of working memory capacity, selective attention, and psychomotor reaction time. Cardiometabolic test variables investigated were blood pressure, fasting blood concentrations of glucose, insulin, blood lipids, inflammatory markers, and markers of oxidative stress. RESULTS: The daily amounts of total polyphenols and DF from the berry beverage were 795 mg and 11g, respectively. There were no polyphenols or DF in the control beverage. The berry intervention reduced total- and LDL cholesterol compared to baseline (both P<0.05), and in comparison to the control beverage (P<0.005 and P<0.01, respectively). The control beverage increased glucose concentrations (P<0.01) and tended to increase insulin concentrations (P = 0.064) from base line, and increased insulin concentrations in comparison to the berry beverage (P<0.05). Subjects performed better in the working memory test after the berry beverage compared to after the control beverage (P<0.05). No significant effects on the other test variables were observed. CONCLUSIONS: The improvements in cardiometabolic risk markers and cognitive performance after the berry beverage suggest preventive potential of berries with respect to type 2 diabetes, cardiovascular disease, and associated cognitive decline. Possibly the polyphenols and DF contributed to the beneficial effects. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01562392.

Oxytocin and Cortisol Levels in Dog Owners and Their Dogs Are Associated with Behavioral Patterns: An Exploratory Study.

We have previously shown that dog-owner interaction results in increasing oxytocin levels in owners and dogs, decreasing cortisol levels in owners but increasing cortisol levels in dogs. The present study aimed to further investigate whether oxytocin and cortisol levels in the previously tested owners and dogs were associated with their behaviors during the interaction experiment. Ten female volunteer dog-owners and their male Labrador dogs participated in a 60 min interaction experiment with interaction taking place during 0-3 min and blood samples for analysis of oxytocin and cortisol were collected at 0, 1, 3, 5, 15, 30, and 60 min. The entire experiment was videotaped and the following variables were noted; the different types (stroking, scratching, patting and activating touch, i.e., scratching and patting combined) as well as the frequency of touch applied by the owner, the number of times the owner touched her dog, the dog's positions and time spent in each position. Correlations were analyzed between the behavioral variables and basal oxytocin levels, maximum oxytocin levels, delta oxytocin levels, basal cortisol levels and cortisol levels at 15 min. Owners with low oxytocin levels before and during the interaction touched their dogs more frequently (0 min: Rs = -0.683, p = 0.042; oxytocin maximum: Rs = -0.783, p = 0.013). The lower the dogs' oxytocin levels during the interaction, the more stroking they received (Rs = -0.717, p = 0.041). The more frequently activating touch was applied by the owner, the higher the dogs' cortisol levels became (15 min: Rs = 0.661, p = 0.038). The higher the owners' maximum oxytocin level the fewer position changes the dogs made (Rs = -0.817, p = 0.007) and the shorter time they spent sitting (Rs = -0.786, p = 0.036), whereas the higher the owners' basal cortisol levels, the longer time the dogs spent standing (0 min: Rs = 0.683, p = 0.041). In conclusion, oxytocin and cortisol levels, both in dogs and in their owners, are associated with the way the owners interact with their dogs and also with behaviors caused by the interaction.

Effects of whole grain rye, with and without resistant starch type 2 supplementation, on glucose tolerance, gut hormones, inflammation and appetite regulation in an 11-14.5 hour perspective; a randomized controlled study in healthy subjects.

BACKGROUND: The prevalence of obesity is increasing worldwide and prevention is needed. Whole grain has shown potential to lower the risk of obesity, cardiovascular disease and type 2 diabetes. One possible mechanism behind the benefits of whole grain is the gut fermentation of dietary fiber (DF), e.g. non-starch polysaccharides and resistant starch (RS), in whole grain. The purpose of the study is to investigate the effect of whole grain rye-based products on glucose- and appetite regulation. METHOD: Twenty-one healthy subjects were provided four rye-based evening test meals in a crossover overnight study design. The test evening meals consisted of either whole grain rye flour bread (RFB) or a 1:1 ratio of whole grain rye flour and rye kernels bread (RFB/RKB), with or without added resistant starch (+RS). White wheat flour bread (WWB) was used as reference evening meal. Blood glucose, insulin, PYY, FFA, IL-6 as well as breath H2 and subjective rating of appetite were measured the following morning at fasting and repeatedly up to 3.5 h after a standardized breakfast consisting of WWB. Ad libitum energy intake was determined at lunch, 14.5 h after evening test and reference meals, respectively. RESULTS: The evening meal with RFB/RKB + RS decreased postprandial glucose- and insulin responses (iAUC) (P < 0.05) and increased the gut hormone PYY in plasma the following morning 0-120 min after the standardized breakfast, compared to WWB (P = 0.01). Moreover, RFB increased subjective satiety and decreased desire to eat, and both RFB and RFB/RKB decreased feeling of hunger (AUC 0-210 min). All rye-based evening meals decreased or tended to decrease fasting FFA (P < 0.05, RFB/RKB: P = 0.057) and increased breath hydrogen concentration (0-120 min, P < 0.001). No effects were noted on energy intake at lunch or inflammatory marker IL-6 (0 + 180 min) after the rye-based evening meals, compared to WWB. CONCLUSION: Whole grain rye bread has the potential to improve cardiometabolic variables in an 11-14.5 h perspective in healthy humans. The combination RFB/RKB + RS positively affected biomarkers of glucose- and appetite regulation in a semi-acute perspective. Meanwhile, RFB and RFB/RKB improved subjective appetite ratings. The effects probably emanate from gut fermentation events. TRIAL REGISTRATION: The study was registered at: ClinicalTrials.gov, register number NCT02347293 ( www.clinicaltrials.gov/ct2/show/NCT02347293 ). Registered 15 January 2015.

Reduction in cardiometabolic risk factors by a multifunctional diet is mediated via several branches of metabolism as evidenced by nontargeted metabolite profiling approach.

SCOPE: Multifunctional diet (MFD), a diet based on multiple functional concepts and ingredients with anti-inflammatory activity, was previously shown to improve different cardiometabolic risk-associated markers in healthy subjects. Here, we assessed the impact of MFD on plasma metabolome and explored associations of the differential metabolites with clinical parameters, searching for metabolic determinants related to the effects of MFD. METHODS AND RESULTS: Forty-four overweight healthy volunteers completed a randomized crossover intervention comparing MFD with a control diet devoid of the active components of MFD. Fasting plasma samples were analyzed with nontargeted metabolite profiling at baseline and at the end (4 wk) of each diet period by LC coupled to quadrupole-TOF-MS system, revealing a vast impact of MFD on metabolic homeostasis. Main metabolite classes affected included acylcarnitines, furan fatty acids, phospholipids (plasmalogens, phosphatidylcholines, phosphatidylethanolamines), and various low-molecular weight products from the bioactivity of gut microbiota. Circulating levels of several of these metabolites correlated with changes in clinical blood lipid biomarkers. CONCLUSIONS: The metabolomics approach revealed that consumption of MFD affected different areas of metabolism, highlighting the impact of a healthy diet on plasma metabolome. This seems linked to reduced cardiometabolic risk and provides mechanistic insight into the effects of MFD.

Rye-Based Evening Meals Favorably Affected Glucose Regulation and Appetite Variables at the Following Breakfast; A Randomized Controlled Study in Healthy Subjects.

BACKGROUND: Whole grain has shown potential to prevent obesity, cardiovascular disease and type 2 diabetes. Possible mechanism could be related to colonic fermentation of specific indigestible carbohydrates, i.e. dietary fiber (DF). The aim of this study was to investigate effects on cardiometabolic risk factors and appetite regulation the next day when ingesting rye kernel bread rich in DF as an evening meal. METHOD: Whole grain rye kernel test bread (RKB) or a white wheat flour based bread (reference product, WWB) was provided as late evening meals to healthy young adults in a randomized cross-over design. The test products RKB and WWB were provided in two priming settings: as a single evening meal or as three consecutive evening meals prior to the experimental days. Test variables were measured in the morning, 10.5-13.5 hours after ingestion of RKB or WWB. The postprandial phase was analyzed for measures of glucose metabolism, inflammatory markers, appetite regulating hormones and short chain fatty acids (SCFA) in blood, hydrogen excretion in breath and subjective appetite ratings. RESULTS: With the exception of serum CRP, no significant differences in test variables were observed depending on length of priming (P>0.05). The RKB evening meal increased plasma concentrations of PYY (0-120 min, P<0.001), GLP-1 (0-90 min, P<0.05) and fasting SCFA (acetate and butyrate, P<0.05, propionate, P = 0.05), compared to WWB. Moreover, RKB decreased blood glucose (0-120 min, P = 0.001), serum insulin response (0-120 min, P<0.05) and fasting FFA concentrations (P<0.05). Additionally, RKB improved subjective appetite ratings during the whole experimental period (P<0.05), and increased breath hydrogen excretion (P<0.001), indicating increased colonic fermentation activity. CONCLUSION: The results indicate that RKB evening meal has an anti-diabetic potential and that the increased release of satiety hormones and improvements of appetite sensation could be beneficial in preventing obesity. These effects could possibly be mediated through colonic fermentation. TRIAL REGISTRATION: ClinicalTrials.gov NCT02093481.

Effects of wheat bran extract rich in arabinoxylan oligosaccharides and resistant starch on overnight glucose tolerance and markers of gut fermentation in healthy young adults.

PURPOSE: Specific combinations of dietary fiber (DF) have been observed to result in improved glucose tolerance at a subsequent standardized breakfast. Arabinoxylan oligosaccharides (AXOS) are considered as DF with prebiotic potential, but so far no studies have investigated their metabolic effects in humans. This randomized cross-over study evaluated the overnight impact of breads containing AXOS-rich wheat bran extract and resistant starch (RS, Hi-Maize), separately or combined, on glucose tolerance, related metabolic parameters and markers of gut fermentation in healthy subjects. METHODS: Evening reference and test products were: (1) reference white wheat flour bread (WWB), WWB supplemented with (2) AXOS and RS (WWB + AXOS + RS), (3) an increased content of either AXOS (WWB + hiAXOS) or (4) RS (WWB + hiRS). At the subsequent standardized breakfast, blood was sampled for 3 h to monitor glucose, insulin, nonesterified fatty acids, glucagon-like peptide (GLP)-1 and GLP-2. Breath hydrogen (H2) and short chain fatty acids (SCFA) were measured as markers of gut fermentation, and subjective appetite was rated using visual analog scales. RESULTS: Dose-dependent decreases in glucose responses were observed with increased AXOS over the duration of 3 h. Insulin sensitivity index was improved in the morning after the WWB + hiAXOS evening meal. An increase in breath H2 concentration and circulating SCFA was observed in the morning after both evening meals containing AXOS. CONCLUSION: The present study indicates that AXOS have the potential of improving glucose tolerance in an overnight perspective and suggested mechanisms are improved insulin sensitivity and increased gut fermentation.

Gut microbiota mediated benefits of barley kernel products on metabolism, gut hormones, and inflammatory markers as affected by co-ingestion of commercially available probiotics: a randomized controlled study in healthy subjects.

BACKGROUND AND AIMS: Barley kernel based products have been shown to induce benefits on blood glucose regulation, cardio-metabolic risk markers and appetite regulating hormones in a time perspective of 11-16 h after intake. The mechanisms have been assigned to gut fermentation of indigestible carbohydrates. The purpose of the present study was to evaluate if the modulatory effects of barley on markers of metabolic- and appetite regulation are affected by a dietary background including a mixture of commercially available probiotics. METHODS: Barley kernel bread was included in the normal diet of 21 healthy subjects in two 4-day intervention periods; with (BB-pro) or without (BB) dietary supplement with a combination of probiotics (Bifidobacterium animalis DN-173 010, Lactobacillus reuteri DSM 17938, and Lactobacillus plantarum 299v). A white wheat flour based bread was included as a reference product (WWB-ref) in a separate 4-day bread intervention period. A cross-over design was applied concerning BB- and WWB-ref; the BB-pro intervention was last in the test sequence. The BB-pro intervention was preceded by 10 days priming with probiotics. The 4 day BB- and WWB-ref intervention periods included dietary supplementation with placebo, and the interventions were preceded with 10 days priming with the placebo. The day after each intervention period, blood samples were collected at fasting and postprandially after a standardized breakfast (0-210 min) for determination of markers of glucose metabolism (blood glucose, serum (s-) insulin), inflammation (s-IL-6, s-IL-18, s-CRP, PAI-1), and concentrations of gut derived hormones involved in satiety and glucose homeostasis (plasma (p-) PYY, p-GLP-1) and intestinal barrier integrity (p-GLP-2). Breath hydrogen was determined as a marker of colonic fermentation. RESULTS: Four days intervention with BB, in comparison to WWB-ref, lowered blood glucose response after a subsequent standardized breakfast (0-210 min, P < 0.05). BB and BB-pro interventions increased p-GLP-1 (0-120 min, P < 0.05) and breath H2 (0-210 min, P < 0.05). BB-pro intervention, in comparison to BB and WWB-ref, increased levels of s-PAI-1 (P < 0.05), and p-GLP-2 (0-210 min, P < 0.05) after the standardized breakfast. CONCLUSIONS: With the exception of increased p-GLP-2 and an unexpected increase in s-PAI-1 concentrations, co-ingestion of a mixture of probiotics did not affect the metabolic outcome of BB; neither positively nor importantly negatively. The study was registered at: ClinicalTrials.gov, register number NCT01718418 (www.clinicaltrials.gov/ct2/show/NCT01718418).

Dietary Fiber-Induced Improvement in Glucose Metabolism Is Associated with Increased Abundance of Prevotella.

The gut microbiota plays an important role in human health by interacting with host diet, but there is substantial inter-individual variation in the response to diet. Here we compared the gut microbiota composition of healthy subjects who exhibited improved glucose metabolism following 3-day consumption of barley kernel-based bread (BKB) with those who responded least to this dietary intervention. The Prevotella/Bacteroides ratio was higher in responders than non-responders after BKB. Metagenomic analysis showed that the gut microbiota of responders was enriched in Prevotella copri and had increased potential to ferment complex polysaccharides after BKB. Finally, germ-free mice transplanted with microbiota from responder human donors exhibited improved glucose metabolism and increased abundance of Prevotella and liver glycogen content compared with germ-free mice that received non-responder microbiota. Our findings indicate that Prevotella plays a role in the BKB-induced improvement in glucose metabolism observed in certain individuals, potentially by promoting increased glycogen storage.

Increased gut hormones and insulin sensitivity index following a 3-d intervention with a barley kernel-based product: a randomised cross-over study in healthy middle-aged subjects.

Certain purified indigestible carbohydrates such as inulin have been shown to stimulate gut-derived hormones involved in glycaemic regulation and appetite regulation, and to counteract systemic inflammation through a gut microbiota-mediated mechanism. Less is known about the properties of indigestible carbohydrates intrinsic to food. The aim of this study was to investigate the possibility to affect release of endogenous gut hormones and ameliorate appetite control and glycaemic control by ingestion of a whole-grain cereal food product rich in NSP and resistant starch in healthy humans. In all, twenty middle-aged subjects were provided with a barley kernel-based bread (BB) or a reference white wheat bread during 3 consecutive days, respectively, in a randomised cross-over design study. At a standardised breakfast the following day (day 4), blood was collected for the analysis of blood (b) glucose regulation, gastrointestinal hormones, markers of inflammation and markers of colonic fermentation; 3 d of intervention with BB increased gut hormones in plasma (p) the next morning at fasting (p-glucagon-like peptide-1; 56%) and postprandially (p-glucagon-like peptide-2; 13% and p-peptide YY; 18%). Breath H2 excretion and fasting serum (s) SCFA concentrations were increased (363 and 18%, respectively), and b-glucose (22%) and s-insulin responses (17%) were decreased after BB intervention. Insulin sensitivity index (ISI(composite)) was also improved (25%) after BB. In conclusion, 3 d of intervention with BB increased systemic levels of gut hormones involved in appetite regulation, metabolic control and maintenance of gut barrier function, as well as improved markers of glucose homoeostasis in middle-aged subjects, altogether relevant for the prevention of obesity and the metabolic syndrome.