Oral glucose sensing in cephalic phase insulin release.

Oral stimulation with foods or food components elicits cephalic phase insulin release (CPIR), which limits postprandial hyperglycemia. Despite its physiological importance, the specific gustatory mechanisms that elicit CPIR have not been clearly defined. While most studies point to glucose and glucose-containing saccharides (e.g., sucrose, maltodextrins) as being the most consistent elicitors, it is not apparent whether this is due to the detection of glucose per se, or to the perceived taste cues associated with these stimuli (e.g., sweetness, starchiness). This study investigated potential sensory mechanisms involved with eliciting CPIR in humans, focusing on the role of oral glucose detection and associated taste. Four stimulus conditions possessing different carbohydrate and taste profiles were designed: 1) glucose alone; 2) glucose mixed with lactisole, a sweet taste inhibitor; 3) maltodextrin, which is digested to starchy- and sweet-tasting products during oral processing; and 4) maltodextrin mixed with lactisole and acarbose, an oral digestion inhibitor. Healthy adults (N = 22) attended four sessions where blood samples were drawn before and after oral stimulation with one of the target stimuli. Plasma c-peptide, insulin, and glucose concentrations were then analyzed. Whereas glucose alone elicited CPIR (one-sample t-test, p < 0.05), it did not stimulate the response in the presence of lactisole. Likewise, maltodextrin alone stimulated CPIR (p < 0.05), but maltodextrin with lactisole and acarbose did not. Together, these findings indicate that glucose is an effective CPIR stimulus, but that an associated taste sensation also serves as an important cue for triggering this response in humans.

Oral stimulation with maltodextrin: Effect on cephalic phase insulin release.

Cephalic phase insulin release (CPIR) occurs following sensory stimulation with food-related stimuli, and has been shown to limit postabsorptive hyperglycemia. While the specific stimuli that elicit CPIR in humans have not been clearly defined, previous research points to sugars as having potential importance. Maltodextrins are a starch-derived food ingredient commonly found in a variety of processed food products. When consumed, salivary α-amylase rapidly cleaves its component saccharides into smaller units, leading to the production of sugars in the mouth. Here, we investigated whether humans elicit CPIR after tasting but not swallowing maltodextrin, and whether the degree of CPIR exhibited is affected by individuals' salivary α-amylase activity. We found that a gelatin-based stimulus containing 22% w/v maltodextrin elicited CPIR in healthy individuals (N = 22) following a modified sham-feeding protocol using both insulin and c-peptide as indices of the response. However, the degree of CPIR measured did not differ across three groupings (low, medium, or high) of effective α-amylase activity by either index. In a follow-up experiment, a subset of participants (N = 14) underwent the same protocol using a gelatin stimulus without maltodextrin, and no observable CPIR ensued. These findings suggest that oral stimulation with maltodextrin elicits CPIR in humans, but that individual differences in effective salivary α-amylase activity may not necessarily be predictive of the degree of CPIR.

Impact of dietary supplementation with resistant dextrin (NUTRIOSE®) on satiety, glycaemia, and related endpoints, in healthy adults.

PURPOSE: Resistant dextrin (RD) supplementation has been shown to alter satiety, glycaemia, and body weight, in overweight Chinese men; however, there are limited data on its effects in other demographic groups. Here, we investigated the effects of RD on satiety in healthy adults living in the United Kingdom. METHODS: 20 normal weight and 16 overweight adults completed this randomised controlled cross-over study. Either RD (14 g/day NUTRIOSE® FB06) or maltodextrin control was consumed in mid-morning and mid-afternoon preload beverages over a 28-day treatment period with crossover after a 28-day washout. During 10-h study visits (on days 1, 14, and 28 of each treatment period), satietogenic, glycaemic and anorectic hormonal responses to provided meals were assessed. RESULTS: Chronic supplementation with RD was associated with higher fasted satiety scores at day 14 (P = 0.006) and day 28 (P = 0.040), compared to control. RD also increased satiety after the mid-morning intervention drink, but it was associated with a reduction in post-meal satiety following both the lunch and evening meals (P < 0.01). The glycaemic response to the mid-morning intervention drink (0-30 min) was attenuated following RD supplementation (P < 0.01). Whilst not a primary endpoint we also observed lower systolic blood pressure at day 14 (P = 0.035) and 28 (P = 0.030), compared to day 1, following RD supplementation in the normal weight group. Energy intake and anthropometrics were unaffected. CONCLUSIONS: RD supplementation modified satiety and glycaemic responses in this cohort, further studies are required to determine longer-term effects on body weight control and metabolic markers. CLINICALTRIALS. GOV REGISTRATION: NCT02041975 (22/01/2014).

Potato By-Products as a Source of Natural Chlorogenic Acids and Phenolic Compounds: Extraction, Characterization, and Antioxidant Capacity.

Total phenolic compounds (TPC) and the chlorogenic acids content of potato by-product extracts of two hydro alcoholic solvents (methanol, ethanol) and two extraction methods (maceration and heating-assisted extraction) were studied. The content of TPC in the extracts was determined spectrometrically according to the Folin-Ciocalteu procedure and calculated as chlorogenic acid equivalents. Soluble phenolic acids, especially the chlorogenic acids, were performed by HPLC. The antioxidant activity of potato by-product extracts was determined by using the total oxygen radical absorbance capacity (ORAC) method. The highest content of TPC was found in raw and lyophilized red waters when using ethanol as a solvent around 57 mg/g fresh weight. Heating-assisted extraction enhances this quantitative increasing. At the given operating conditions, unpeeled potato samples exhibit a higher TPC than peeled ones, showing that TPC are accumulated in skin tissue. The greatest amount of chlorogenic acid (Caffeoyl-Quinic Acids, 3, 4, 5 CQA), mainly the 5-CQA (870 ± 39.66 µg/g WM for wet matter versus DM dry matter), was obtained in the pellets and lyophilized fresh peels (skin vs. flesh). In addition, the greatest amounts of chlorogenic acids were found when potato peels were extracted with methanol. Heating-assisted extraction improved the chlorogenic acid concentration of the potato peel extracts. The total ORAC amounts recorded in the different potato fractions varied between 1500 and 1650 µM TE/g. They were higher than those of some fruits, vegetables, nuts, cereals, and sweet potato cultivar. The good correlation coefficient found between TPC, chlorogenic acids determination, and the ORAC capacity indicates that the TPC can be used as a good indicator of the antioxidant capacity of potato by-products.

Cyclodextrins as Emerging Therapeutic Tools in the Treatment of Cholesterol-Associated Vascular and Neurodegenerative Diseases.

Cardiovascular diseases, like atherosclerosis, and neurodegenerative diseases affecting the central nervous system (CNS) are closely linked to alterations of cholesterol metabolism. Therefore, innovative pharmacological approaches aiming at counteracting cholesterol imbalance display promising therapeutic potential. However, these approaches need to take into account the existence of biological barriers such as intestinal and blood-brain barriers which participate in the organ homeostasis and are major defense systems against xenobiotics. Interest in cyclodextrins (CDs) as medicinal agents has increased continuously based on their ability to actively extract lipids from cell membranes and to provide suitable carrier system for drug delivery. Many novel CD derivatives are constantly generated with the objective to improve CD bioavailability, biocompatibility and therapeutic outcomes. Newly designed drug formulation complexes incorporating CDs as drug carriers have demonstrated better efficiency in treating cardiovascular and neurodegenerative diseases. CD-based therapies as cholesterol-sequestrating agent have recently demonstrated promising advances with KLEPTOSE® CRYSMEB in atherosclerosis as well as with the 2-hydroxypropyl-ß-cyclodextrin (HPßCD) in clinical trials for Niemann-Pick type C disease. Based on this success, many investigations evaluating the therapeutical beneficial of CDs in Alzheimer's, Parkinson's and Huntington's diseases are currently on-going.

Modulation of the faecal microbiome of healthy adult dogs by inclusion of potato fibre in the diet.

Inclusion of fermentable fibres in the diet can have an impact on the hindgut microbiome and provide numerous health benefits to the host. Potato fibre (PF), a co-product of potato starch isolation, has a favourable chemical composition of pectins, resistant and digestible starch, cellulose, and hemicelluloses. The objective of the present study was to evaluate the effect of increasing dietary PF concentrations on the faecal microbiome of healthy adult dogs. Fresh faecal samples were collected from ten female dogs with hound bloodlines (6·13 (SEM 0·17) years; 22·0 (SEM 2·1) kg) fed five test diets containing graded concentrations of PF (0, 1·5, 3, 4·5 or 6% as-fed; Roquette Frères) in a replicated 5 × 5 Latin square design. Extraction of DNA was followed by amplification of the V4-V6 variable region of the 16S rRNA gene using barcoded primers. Sequences were classified into taxonomic levels using Basic Local Alignment Search Tool (BLASTn) against a curated GreenGenes database. Inclusion of PF increased (P< 0·05) the faecal proportions of Firmicutes, while those of Fusobacteria decreased (P< 0·05). Similar shifts were observed at the genus level and were confirmed by quantitative PCR (qPCR) analysis. With increasing concentrations of PF, faecal proportions of Faecalibacterium increased (P< 0·05). Post hoc Pearson's correlation analysis showed positive (P< 0·05) correlations with Bifidobacterium spp. and butyrate production and Lactobacillus spp. concentrations. Overall, increases in the proportion of Faecalibacterium (not Lactobacillus/Bifidobacterium, as confirmed by qPCR analysis) and faecal SCFA concentrations with increasing dietary PF concentrations suggest that PF is a possible prebiotic fibre.

Slow Digestible Starch in Native Pea Starch (Pisum sativum L.) Lowers Glycemic Response with No Adverse Effects on Gastrointestinal Symptoms in Healthy Adults.

Diabetes prevalence achieved 470B in 2021. Diabetics are looking for foods that allow them to better manage the postprandial glycemia. Owing to its large amylose fraction, pea starch may contribute to formulate recipes with a lower glycemic index (GI). This study measured the rapidly, slowly digested and resistant fractions in pea starch and in a powder mix recipe. Starch fractions were determined according to the Englyst methodology. A nonblind repeat measure crossover design trial in healthy humans was used to study the GI of pea starch and maltodextrin powder mix recipes against glucose. Gastrointestinal symptoms were measured. Thirteen healthy volunteers aged 18-60 years with body mass index <30 kg/m2 and fasting blood glucose <6.1 mmol/L participated in the study. They consumed 25 g available carbohydrate portions of the test products. Blood glucose was measured at -5 and 0 min before consumption till 180 min after starting to eat. The slow digestible starch (SDS) content of native pea starch was 30% of the total starch content. The pea-based powder mix recipe contained 25% SDS in comparison with 9% for the maltodextrin-based recipe. The glucose response after pea starch was significantly lower compared with maltodextrin. The glucose response after pea starch recipe was significantly lower compared with maltodextrin recipe. There was no significant difference in mean scores for well-being and gastrointestinal symptoms after consumption of pea starch and maltodextrin or between the two recipes. In conclusion, this study has demonstrated the presence of high SDS content in pea starch, which reduced postprandial glycemic response compared with maltodextrin. The pea starch recipe did not induce any negative gastrointestinal symptoms. Pea starch may, therefore, prove to be a beneficial ingredient in developing food products for improving glycemic control without undesirable side effects.

Impact of a resistant dextrin with a prolonged oxidation pattern on day-long ghrelin profile.

OBJECTIVES: The effects of a new resistant dextrin ingested at breakfast on day-long metabolic parameters and ghrelin profile at subsequent lunch were investigated. METHODS: In this randomized, single-blinded, crossover study, 12 healthy men ingested a standardized breakfast with 50 g of NUTRIOSE 10, a resistant dextrin (RD), or of maltodextrin (Malto) and a standardized lunch 5 hours later. Both products (RD and Malto) were derived from corn naturally rich in (13)C to follow their metabolic fate (by using stable isotope analysis). Oxidation and fermentation patterns were assessed by simultaneous (13)CO(2)/H(2) breath testing. The appearance of exogenous (13)C-glucose in plasma, glycemia, insulinemia, nonesterified fatty acids (NEFAs), and ghrelin concentrations were measured for 10 hours following breakfast ingestion. RESULTS: With RD, H(2) excretion (fermentation) was significantly enhanced compared with Malto, whereas the appearance of (13)CO(2) (oxidation) was significantly prolonged (p < 0.0001). Following breakfast, ghrelin secretion was significantly less inhibited and NEFA concentration was higher with RD (p < 0.05), but unexpectedly, both remained lower after lunch and up to T600 minutes. According to the reduced bioavailability of RD compared with Malto, the appearance of (13)C-glucose in plasma (p < 0.0001) and glycemic and insulinemic responses to breakfast (p < 0.05) were significantly reduced. CONCLUSIONS: Ingestion of this new resistant dextrin at breakfast decreased ghrelin concentrations in response to the subsequent lunch, even if the caloric load ingested at breakfast was lower. This effect may be linked to the prolonged fermentation/oxidation pattern seen in the late postprandial phase (up to 10 hours after ingestion at breakfast), and thus prolonged energy release with the resistant dextrin.

Short-term digestive tolerance of high-dose of NUTRIOSE®FB10 in adult.

NUTRIOSE®FB10 is a dextrin considered a dietary fiber. The present study aims to assess the digestive tolerance of a high dose of NUTRIOSE®FB10 consumed over the day, and its effect on digestive symptoms. In a randomized, double-blind, cross-over trial, 12 healthy men ingested 1 l/day orange juice containing 50 g either NUTRIOSE®FB10 or placebo (maltodextrin) in three equal doses at breakfast, lunch and 4:00 pm meal. Bloating, borborygmus, flatulence, nausea feelings, stomach ache, transit and stool consistency were evaluated at different times after the first consumption. Questionnaires on well-being and bowel movement were completed at 24 and 48 h. For all data except stool consistency, the area under the curve, the maximum score and the time of this maximum were calculated. For stool consistency, the mean score over 48 h was determined. There was no statistical difference between NUTRIOSE®FB10 and placebo on each criterion. NUTRIOSE®FB10 is well tolerated during a single day at 50 g divided into three doses.

Effects of NUTRIOSE® dietary fiber supplementation on body weight, body composition, energy intake, and hunger in overweight men.

The objective of the present study was to determine the effectiveness of a soluble dietary fiber, NUTRIOSE(®), on body weight, body composition, energy intake and hunger in overweight Chinese men. The volunteers were randomized in double-blind fashion to 250 ml fruit juice supplemented with NUTRIOSE(®) (Test, n = 60) or a maltodextrin (Control, n = 60) at a dosage of 17 g twice daily for 12 weeks. Body weight, body composition were performed at 0, 4, 8 and 12 weeks while daily energy intake and hunger were assessed every 3 days. Test subjects had reductions in body weight (1.5 kg, P < 0.001), body mass index (0.5 kg/m(2), P < 0.001) and body fat percentage (0.3%, P < 0.001) versus Controls. NUTRIOSE(®) supplementation resulted in a lower daily energy intake (3,079 kJ/day, P < 0.001) with group differences noted as early as 3 days. Test subjects reported less hunger across the study period versus Controls (P < 0.01). NUTRIOSE(®) supplementation for 12 weeks results in body composition improvements and reduces body weight, energy intake and hunger in overweight men.

Cholesterol-lowering effect of non-viscous soluble dietary fiber Nutriose6 in moderately hypercholesterolemic hamsters.

NUTRIOSE6 is a new wheat starch-based low-digestible carbohydrate. This study investigated the effect of this soluble non-viscous fiber on cholesterol metabolism. Hamsters fed with 0.25% cholesterol-enriched diet (CHO) were given graded amounts of NUTRIOSE6, i.e., 0% (cellulose, CHO), 3% (N3), 6% (N6) or 9% (N9) (w:w). As compared to CHO diet, 9% NUTRIOSE6 significantly lowered plasma and LDL cholesterol by 14.5 and 23.8%, respectively. The LDL-cholesterol lowering effect was also significant with the 6% dose (-21.4%). NUTRIOSE6 diets prevented hepatic cholesterol accumulation (-10 to -20%) and significantly decreased bile cholesterol (-47 to -68%) and phospholipids (-30 to -45%) concentrations. The 9% NUTRIOSE6 diet significantly decreased the rate of dietary cholesterol absorption (-25%) and markedly stimulated faecal neutral sterol (+81%) and bile salts (+220%) excretion. No significant change in cholesterol 7-alpha-hydroxylase or LDL-receptor activities was observed whereas 3-hydroxy-3-methylglutaryl-coenzyme A reductase activity was reduced by 29%. Reduced cholesterol and bile salt absorptions and lowered cholesterol synthesis are likely mechanisms underlying the cholesterol lowering effect of NUTRIOSE6. Results suggest the use of NUTRIOSE6 as a new dietary cholesterol-lowering agent that should be tested in humans as treatment and evenly prevention of mild hypercholesterolemia.

Short-term digestive tolerance of chocolate formulated with maltitol in children.

INTRODUCTION: Polyols are molecules of interest for food industries because of their technological and nutritional properties. Maltitol is known for its non-acidogenic and low-energetic properties. Our primary objective was to evaluate the digestive tolerance of maltitol in children. The secondary objective was to compare the organoleptic properties of maltitol and sucrose in chocolate. METHOD: Healthy children were included in a double-blind, randomized parallel study versus placebo. The subjects received one dose of either maltitol or sucrose chocolate per week. Increasing doses were tested from 5 to 15 g maltitol in chocolate. Abdominal pain, rumbling, bloating and flatulence scores were evaluated using visual analog scales. RESULTS: Some statistical differences on intestinal parameters were observed in the maltitol group compared with placebo, mainly concerning flatulence scores. Nevertheless, these scores remained low and could be considered minor. CONCLUSION: Our results suggest that maltitol was well tolerated in children at 15 g in one intake.

Characterization of ethylcellulose: starch-based film coatings for colon targeting.

BACKGROUND: The site-specific delivery of drugs to the colon can be highly advantageous for various applications, including the local treatment of inflammatory bowel diseases. The aim of this study was to provide efficient tools that can be used to easily adjust the key properties of novel polymeric film coatings allowing for colon targeting. METHODS: Free films based on blends of ethylcellulose and different types of starch derivatives (partially being pregelatinized, acetylated, and/or hydroxypropylated) were prepared and characterized. RESULTS: The key properties of the polymeric systems can effectively be adjusted by varying the polymer blend ratio and type of starch derivative. This includes the water uptake and dry mass loss kinetics as well as the mechanical properties of the films before and upon exposure to aqueous media simulating the contents of the upper GIT. CONCLUSION: Broad ranges of film coating properties can easily be provided, being adapted to the needs of the respective drug treatment.

Impact of sugar replacers on cognitive performance and function in rats.

Glycaemic responses to the dextrin NUTRIOSE 6 (Dex) and the MALTISORB maltitol (Mal) have been studied previously but their effects on vigilance and cognitive performances are still not known. The present study assesses dose-related glycaemic responses following Dex administration and the hypothesis that Dex and Mal could modulate the glycaemic response, improve vigilance under stress conditions and improve cognitive performances in rats. The glycaemic responses following Dex and corn syrup GLUCIDEX IT 21 (CoS) solutions at 0.3, 0.5 and 1.0 g/kg body weight administered by oral administration (experiment 1) and glycaemic responses to three cereal bars (standard (CoS), Dex or Dex/Mal bar) (experiment 2) were evaluated. Rats having eaten cereal bars were submitted to vigilance and aversive light stimulus avoidance conditioning tests to assess their vigilance and cognitive performances. The first experiment showed that the glycaemic response to both products is dose-related and that CoS induced a glycaemic response three times higher than the Dex response. The second experiment showed the same glycaemic response for the three cereal bar-treated rats. Yet, an increase in the vigilance of Dex/Mal-treated rats as well as a better discrimination between two levers in the cognitive test for Dex- and Dex/Mal-treated rats were noticed. These results suggest that the glycaemic response is not the only factor to be considered in predicting the efficiency of a food ingredient on vigilance and cognitive performances: these behaviours are improved after Dex- and Mal-prepared cereal bar ingestion whereas the glycaemic response does not differ from the CoS-prepared bar.

ß-Cyclodextrins Decrease Cholesterol Release and ABC-Associated Transporter Expression in Smooth Muscle Cells and Aortic Endothelial Cells.

Atherosclerosis is an inflammatory disease that leads to an aberrant accumulation of cholesterol in vessel walls forming atherosclerotic plaques. During this process, the mechanism regulating complex cellular cholesterol pools defined as the reverse cholesterol transport (RCT) is altered as well as expression and functionality of transporters involved in this process, namely ABCA1, ABCG1, and SR-BI. Macrophages, arterial endothelial and smooth muscle cells (SMCs) have been involved in the atherosclerotic plaque formation. As macrophages are widely described as the major cell type forming the foam cells by accumulating intracellular cholesterol, RCT alterations have been poorly studied at the arterial endothelial cell and SMC levels. Amongst the therapeutics tested to actively counteract cellular cholesterol accumulation, the methylated ß-cyclodextrin, KLEPTOSE® CRYSMEß, has recently shown promising effects on decreasing the atherosclerotic plaque size in atherosclerotic mouse models. Therefore we investigated in vitro the RCT process occurring in SMCs and in arterial endothelial cells (ABAE) as well as the ability of some modified ß-CDs with different methylation degree to modify RCT in these cells. To this aim, cells were incubated in the presence of different methylated ß-CDs, including KLEPTOSE® CRYSMEß. Both cell types were shown to express basal levels of ABCA1 and SR-BI whereas ABCG1 was solely found in ABAE. Upon CD treatments, the percentage of membrane-extracted cholesterol correlated to the methylation degree of the CDs independently of the lipid composition of the cell membranes. Decreasing the cellular cholesterol content with CDs led to reduce the expression levels of ABCA1 and ABCG1. In addition, the cholesterol efflux to ApoA-I and HDL particles was significantly decreased suggesting that cells forming the blood vessel wall are able to counteract the CD-induced loss of cholesterol. Taken together, our observations suggest that methylated ß-CDs can significantly reduce the cellular cholesterol content of cells forming atherosclerotic lesions and can subsequently modulate the expression of ABC transporters involved in RCT. The use of methylated ß-CDs would represent a valuable and efficient tool to interfere with atherosclerosis pathogenesis in patients, nonetheless their mode of action still needs further investigations to be fully understood and finely controlled at the cellular level.

NUTRALYS(®) pea protein: characterization of in vitro gastric digestion and in vivo gastrointestinal peptide responses relevant to satiety.

BACKGROUND: Pea protein (from Pisum sativum) is under consideration as a sustainable, satiety-inducing food ingredient. OBJECTIVE: In the current study, pea-protein-induced physiological signals relevant to satiety were characterized in vitro via gastric digestion kinetics and in vivo by monitoring post-meal gastrointestinal hormonal responses in rats. DESIGN: Under in vitro simulated gastric conditions, the digestion of NUTRALYS(®) pea protein was compared to that of two dairy proteins, slow-digestible casein and fast-digestible whey. In vivo, blood glucose and gastrointestinal hormonal (insulin, ghrelin, cholecystokinin [CCK], glucagon-like peptide 1 [GLP-1], and peptide YY [PYY]) responses were monitored in nine male Wistar rats following isocaloric (11 kcal) meals containing 35 energy% of either NUTRALYS(®) pea protein, whey protein, or carbohydrate (non-protein). RESULTS: In vitro, pea protein transiently aggregated into particles, whereas casein formed a more enduring protein network and whey protein remained dissolved. Pea-protein particle size ranged from 50 to 500 µm, well below the 2 mm threshold for gastric retention in humans. In vivo, pea-protein and whey-protein meals induced comparable responses for CCK, GLP-1, and PYY, that is, the anorexigenic hormones. Pea protein induced weaker initial, but equal 3-h integrated ghrelin and insulin responses than whey protein, possibly due to the slower gastric breakdown of pea protein observed in vitro. Two hours after meals, CCK levels were more elevated in the case of protein meals compared to that of non-protein meals. CONCLUSIONS: These results indicate that 1) pea protein transiently aggregates in the stomach and has an intermediately fast intestinal bioavailability in between that of whey and casein; 2) pea-protein- and dairy-protein-containing meals were comparably efficacious in triggering gastrointestinal satiety signals.

Intrinsic immunomodulatory effects of low-digestible carbohydrates selectively extend their anti-inflammatory prebiotic potentials.

The beneficial effects of carbohydrate-derived fibers are mainly attributed to modulation of the microbiota, increased colonic fermentation, and the production of short-chain fatty acids. We studied the direct immune responses to alimentary fibers in in vitro and in vivo models. Firstly, we evaluated the immunomodulation induced by nine different types of low-digestible fibers on human peripheral blood mononuclear cells. None of the fibers tested induced cytokine production in baseline conditions. However, only one from all fibers almost completely inhibited the production of anti- and proinflammatory cytokines induced by bacteria. Secondly, the impact of short- (five days) and long-term (three weeks) oral treatments with selected fibers was assessed in the trinitrobenzene-sulfonic acid colitis model in mice. The immunosuppressive fiber significantly reduced levels of inflammatory markers over both treatment periods, whereas a nonimmunomodulatory fiber had no effect. The two fibers did not differ in terms of the observed fermentation products and colonic microbiota after three weeks of treatment, suggesting that the anti-inflammatory action was not related to prebiotic properties. Hence, we observed a direct effect of a specific fiber on the murine immune system. This intrinsic, fiber-dependent immunomodulatory potential may extend prebiotic-mediated protection in inflammatory bowel disease.

Treatment with KLEPTOSE® CRYSMEB reduces mouse atherogenesis by impacting on lipid profile and Th1 lymphocyte response.

The ability of pharmacological agents to target both "classical" risk factors and inflammation may be key for successful outcomes in the prevention and treatment of atherogenesis. Among the promising drugs interfering with cholesterol metabolism, we investigated whether methyl beta-cyclodextrin (KLEPTOSE® CRYSMEB) could positively impact on atherogenesis, lipid profile and atherosclerotic plaque inflammation in ApoE-/- mice. Eleven-week old ApoE-/- mice were fed either a normal diet (N.D.) or a high-cholesterol diet (H.D.), resulting in different levels of hypercholesterolemia. KLEPTOSE® CRYSMEB (40mg/kg) or vehicle was intraperitoneally administrated 3 times per week in the last 16weeks before euthanasia in mice under N.D. and in the last 11weeks under H.D. Treatment with KLEPTOSE® CRYSMEB reduced triglyceride serum levels in both atherogenesis mouse models. In H.D. mice, treatment with KLEPTOSE® CRYSMEB increased HDL-cholesterol levels and reduced free fatty acids and spleen weight. In both mouse models, treatment with KLEPTOSE® CRYSMEB reduced atherosclerotic plaque size in thoraco-abdominal aortas and intraplaque T lymphocyte content, but did not induce relevant improvements in other histological parameters of vulnerability (macrophage, neutrophil, MMP-9 and collagen content). Conversely and more markedly in H.D. mice, treatment with KLEPTOSE® CRYSMEB was associated with a reduction in genetic markers of Th1-mediated immune response. In vitro, KLEPTOSE® CRYSMEB dose-dependently abrogated Th1 proliferation and IFNγ release. In conclusion, treatment with KLEPTOSE® CRYSMEB reduced atherosclerotic plaque size by improving triglyceride serum levels and Th1-mediated response. These results indicate this drug as a potential tool for blocking atheroprogression associated with different severity degrees of hypercholesterolemia.

In vitro fermentation of NUTRIOSE(®) FB06, a wheat dextrin soluble fibre, in a continuous culture human colonic model system.

Wheat dextrin soluble fibre may have metabolic and health benefits, potentially acting via mechanisms governed by the selective modulation of the human gut microbiota. Our aim was to examine the impact of wheat dextrin on the composition and metabolic activity of the gut microbiota. We used a validated in vitro three-stage continuous culture human colonic model (gut model) system comprised of vessels simulating anatomical regions of the human colon. To mimic human ingestion, 7 g of wheat dextrin (NUTRIOSE(®) FB06) was administered to three gut models, twice daily at 10.00 and 15.00, for a total of 18 days. Samples were collected and analysed for microbial composition and organic acid concentrations by 16S rRNA-based fluorescence in situ hybridisation and gas chromatography approaches, respectively. Wheat dextrin mediated a significant increase in total bacteria in vessels simulating the transverse and distal colon, and a significant increase in key butyrate-producing bacteria Clostridium cluster XIVa and Roseburia genus in all vessels of the gut model. The production of principal short-chain fatty acids, acetate, propionate and butyrate, which have been purported to have protective, trophic and metabolic host benefits, were increased. Specifically, wheat dextrin fermentation had a significant butyrogenic effect in all vessels of the gut model and significantly increased production of acetate (vessels 2 and 3) and propionate (vessel 3), simulating the transverse and distal regions of the human colon, respectively. In conclusion, wheat dextrin NUTRIOSE(®) FB06 is selectively fermented in vitro by Clostridium cluster XIVa and Roseburia genus and beneficially alters the metabolic profile of the human gut microbiota.