Wheat-derived arabinoxylan oligosaccharides with prebiotic effect increase satietogenic gut peptides and reduce metabolic endotoxemia in diet-induced obese mice

BACKGROUND: Alterations in the composition of gut microbiota -known as dysbiosis- have been proposed to contribute to the development of obesity, thereby supporting the potential interest of nutrients acting on the gut microbes to produce beneficial effect on host energetic metabolism. Non-digestible fermentable carbohydrates present in cereals may be interesting nutrients able to influence the gut microbiota composition.OBJECTIVE AND DESIGN: The aim of the present study was to test the prebiotic potency of arabinoxylan oligosaccharides (AXOS) prepared from wheat bran in a nutritional model of obesity, associated with a low-grade chronic systemic inflammation. Mice were fed either a control diet or a high fat (HF) diet, or a HF diet supplemented with AXOS during 8 weeks.RESULTS: AXOS supplementation induced caecal and colon enlargement associated with an important bifidogenic effect. It increased the level of circulating satietogenic peptides produced by the colon (peptide YY and glucagon-like peptide-1), and coherently counteracted HF-induced body weight gain and fat mass development. HF-induced hyperinsulinemia and the Homeostasis Model Assessment of insulin resistance were decreased upon AXOS feeding. In addition, AXOS reduced HF-induced metabolic endotoxemia, macrophage infiltration (mRNA of F4/80) in the adipose tissue and interleukin 6 (IL6) in the plasma. The tight junction proteins (zonula occludens 1 and claudin 3) altered upon HF feeding were upregulated by AXOS treatment suggesting that the lower inflammatory tone was associated with the improvement of gut barrier function.CONCLUSION: Together, these findings suggest that specific non-digestible carbohydrates produced from cereals such as AXOS constitute a promising prebiotic nutrient in the control of obesity and related metabolic disorders.</p

Exploring the endocannabinoidome in genetically obese (ob/ob) and diabetic (db/db) mice: Links with inflammation and gut microbiota

Background: Obesity and type 2 diabetes are two interrelated metabolic disorders characterized by insulin resistance and a mild chronic inflammatory state. We previously observed that leptin (ob/ob) and leptin receptor (db/db) knockout mice display a distinct inflammatory tone in the liver and adipose tissue. The present study aimed at investigating whether alterations in these tissues of the molecules belonging to the endocannabinoidome (eCBome), an extension of the endocannabinoid (eCB) signaling system, whose functions are important in the context of metabolic disorders and inflammation, could reflect their different inflammatory phenotypes. Results: The basal eCBome lipid and gene expression profiles, measured by targeted lipidomics and qPCR transcriptomics, respectively, in the liver and subcutaneous or visceral adipose tissues, highlighted a differentially altered eCBome tone, which may explain the impaired hepatic function and more pronounced liver inflammation remarked in the ob/ob mice, as well as the more pronounced inflammatory state observed in the subcutaneous adipose tissue of db/db mice. In particular, the levels of linoleic acid-derived endocannabinoid-like molecules, of one of their 12-lipoxygenase metabolites and of Trpv2 expression, were always altered in tissues exhibiting the highest inflammation. Correlation studies suggested the possible interactions with some gut microbiota bacterial taxa, whose respective absolute abundances were significantly different between ob/ob and the db/db mice. Conclusions: The present findings emphasize the possibility that bioactive lipids and the respective receptors and enzymes belonging to the eCBome may sustain the tissue-dependent inflammatory state that characterizes obesity and diabetes, possibly in relation with gut microbiome alterations

Determination of digestible energy values and fermentabilities of dietary fibre supplements: a European interlaboratory study in vivo

The performance of methods to determine energy conversion factors for dietary fibre (DF) supplements and fermentability (D) values of their non-starch polysaccharides (NSP) was investigated. Heats of combustion, digestible energy (DE) and D values were determined on five DF supplements in five European laboratories on five separate occasions. In each instance the DF supplements were fed to juvenile male VVistar rats at two doses, 50 and 100 g/kg basal diet, for 3 weeks with food and faeces collected in the 3rd week. Among-laboratory variations in heats of combustion (DHC<) were <2%. DE values (kJ/g dry weight) at the upper and lower doses respectively were: 10·4 and 9·9 for a high-methoxyl apple pectin, 9·5 and 9·4 for a sugar-beet DF supplement, 12·2 and 12·7 for soyabean DF supplement, 38 and 4·0 for maize bran, and 0·3 and 0·3 for Solka-floc cellulose. Variations among laboratories, among occasions and among animals were <1, <2 and <2·5 kJ/g respectively. The among-occasion: among-laboratory variance ratio for DE was 0·5, suggesting the method performed equally well in all laboratories. There was no evidence of learning or fatigue in the performance of the method. D values were also independent of dose and at the high and lower doses were: pectin 0·92 and 0·95, sugar-beet NSP 0·68 and 0·68, soyabean NSP 0·86 and 0·88, maize bran 0·17 and 0·18, cellulose 0·07 and 0·06. Among-laboratory variance tended to increase with decreasing fermentability and ranged from 0·03 to 0·18. The DE and D data were not significantly different from a previously proposed relationship DE = 0·7 × DHc × D, where DHc is the heat of combustion of the supplement. We conclude that while the among-laboratory variation in the D of difficult-to-ferment NSP is too large for the reliable prediction of energy value the method for the direct determination of DE is both reproducible and repeatable, that DE is independent of dosage of DF supplement up to 100 g/kg diet, and that it is safe to discriminate between energy values with a precision of 3 kJ/g. The conversion of both DE and D to net metabolizable energy for the purpose of food labelling, tables and databases is describe

Oligofructose Promotes Satiety in Healthy Human: A Pilot Study.

Objective: The administration of a fermentable dietary fibre (oligofructose) in rats increases satietogenic gut peptides and lowered spontaneous energy intake. The aim of the study was to assess the relevance of those effects of oligofructose on satiety and energy intake in humans. Design: Single-blinded, crossover, placebo-controlled design, pilot study. Subjects: Volunteers included five men and five women aged 21-39 years, BMI ranging from 18.5 to 27.4 kg/m 2 , were randomly assigned as described below. Interventions: Subjects were included in two 2-week experimental phases during which they received either fibre (oligofructose (OFS)) or placebo (dextrine maltose (DM)); a 2-week washout period was included between crossover phases. In total, 8 g OFS or 8 g DM were ingested twice daily (16 g/day in total). Energy intake, hunger, satiety, fullness and prospective food consumption were assessed with analogue scales at the end of each experimental phase. Results: During breakfast, OFS significantly increases the satiety (P ¼ 0.04) without any difference on other sensations as compared to DM treatment periods. After lunch, no significant differences are observed between treatment period. At dinner, OFS significantly increases satiety (P ¼ 0.04), reduces hunger (P ¼ 0.04) and prospective food consumption (P ¼ 0.05). The energy intake at breakfast and lunch are significantly lower (P ¼ 0.01, 0.03, respectively) after OFS treatment than after DM treatment. Total energy intake per day is 5% lower during OFS than in DM period. Conclusion: Oligofructose treatment increases satiety following breakfast and dinner, reduces hunger and prospective food consumption following dinner. This pilot study presents a rationale to propose oligofructose supplements in the management of food intake in overweight and obese patients. Sponsorship: This project is supported by an FSR grant from the Université catholique de Louvain

Effects of fructooligosaccharides on cecum polyamine concentration and gut maturation in early-weaned piglets

Polyamines are molecules involved in cell growth and differentiation and are produced by bacterial metabolism. However, their production and effects by the microbiota selected by fructooligosaccharides consumption are controversial. In this study, we investigated the influence of supplementation of fructooligosaccharides on the cecal polyamine production by the microflora selected, and its effect on gut maturation in newborn piglets. Twenty piglets were fed a control formula (n = 10) or a formula supplemented with fructooligosaccharides (8 g/l) (n = 10) for 13 days. Colony-forming unit’s count of cecal content was done in different media. Several intestinal development parameters were measured as well as the polyamine concentration in the cecal mucosa and cecal content. A dose-dependent study on in vitro polyamine production by fructooligosaccharides addition to the isolated cecal content was performed. Bifidogenic activity of fructooligosaccharides increased polyamine concentration in the cecal content, mainly putrescine, with no beneficial effect on gut maturation. Bifidobacterium spp. were able to produce polyamines, but they were not the most significant bacterial producer of polyamines in the cecum of piglets fed fructooligosaccharides. Bifidogenic activity of fructooligosaccharides did not lead to an increase in gut maturation in piglets of 15 days of age although polyamines were increased in the cecal content

Changes in gut microbiota control inflammation in obese mice through a mechanism involving GLP-2-driven improvement of gut permeability

Background and aims: Obese and diabetic mice display enhanced intestinal permeability and metabolic endotoxaemia that participate in the occurrence of metabolic disorders. Our recent data support the idea that a selective increase of Bifidobacterium spp. reduces the impact of high-fat diet-induced metabolic endotoxaemia and inflammatory disorders. Here, we hypothesised that prebiotic modulation of gut microbiota lowers intestinal permeability, by a mechanism involving glucagon-like peptide-2 (GLP-2) thereby improving inflammation and metabolic disorders during obesity and diabetes. Methods: Study 1: ob/ob mice (Ob-CT) were treated with either prebiotic (Ob-Pre) or non-prebiotic carbohydrates as control (Ob-Cell). Study 2: Ob-CT and Ob-Pre mice were treated with GLP-2 antagonist or saline. Study 3: Ob-CT mice were treated with a GLP-2 agonist or saline. We assessed changes in the gut microbiota, intestinal permeability, gut peptides, intestinal epithelial tight-junction proteins ZO-1 and occludin (qPCR and immunohistochemistry), hepatic and systemic inflammation. Results: Prebiotic-treated mice exhibited a lower plasma lipopolysaccharide (LPS) and cytokines, and a decreased hepatic expression of inflammatory and oxidative stress markers. This decreased inflammatory tone was associated with a lower intestinal permeability and improved tight-junction integrity compared to controls. Prebiotic increased the endogenous intestinotrophic proglucagon-derived peptide (GLP-2) production whereas the GLP-2 antagonist abolished most of the prebiotic effects. Finally, pharmacological GLP-2 treatment decreased gut permeability, systemic and hepatic inflammatory phenotype associated with obesity to a similar extent as that observed following prebiotic-induced changes in gut microbiota. Conclusion: We found that a selective gut microbiota change controls and increases endogenous GLP-2 production, and consequently improves gut barrier functions by a GLP-2-dependent mechanism, contributing to the improvement of gut barrier functions during obesity and diabetes

Prebiotic Effects of Wheat Arabinoxylan Related to the Increase in Bifidobacteria, Roseburia and Bacteroides/Prevotella in Diet-Induced Obese Mice

BACKGROUND: Alterations in the composition of gut microbiota--known as dysbiosis--has been proposed to contribute to the development of obesity, thereby supporting the potential interest of nutrients targeting the gut with beneficial effect for host adiposity. We test the ability of a specific concentrate of water-extractable high molecular weight arabinoxylans (AX) from wheat to modulate both the gut microbiota and lipid metabolism in high-fat (HF) diet-induced obese mice. METHODOLOGY/PRINCIPAL FINDINGS: Mice were fed either a control diet (CT) or a HF diet, or a HF diet supplemented with AX (10% w/w) during 4 weeks. AX supplementation restored the number of bacteria that were decreased upon HF feeding, i.e. Bacteroides-Prevotella spp. and Roseburia spp. Importantly, AX treatment markedly increased caecal bifidobacteria content, in particular Bifidobacterium animalis lactis. This effect was accompanied by improvement of gut barrier function and by a lower circulating inflammatory marker. Interestingly, rumenic acid (C18:2 c9,t11) was increased in white adipose tissue due to AX treatment, suggesting the influence of gut bacterial metabolism on host tissue. In parallel, AX treatment decreased adipocyte size and HF diet-induced expression of genes mediating differentiation, fatty acid uptake, fatty acid oxidation and inflammation, and decreased a key lipogenic enzyme activity in the subcutaneous adipose tissue. Furthermore, AX treatment significantly decreased HF-induced adiposity, body weight gain, serum and hepatic cholesterol accumulation and insulin resistance. Correlation analysis reveals that Roseburia spp. and Bacteroides/Prevotella levels inversely correlate with these host metabolic parameters. CONCLUSIONS/SIGNIFICANCE: Supplementation of a concentrate of water-extractable high molecular weight AX in the diet counteracted HF-induced gut dysbiosis together with an improvement of obesity and lipid-lowering effects. We postulate that hypocholesterolemic, anti-inflammatory and anti-obesity effects are related to changes in gut microbiota. These data support a role for wheat AX as interesting nutrients with prebiotic properties related to obesity prevention