Barley- and Legume Products Beneficially Affect Metabolic Responses and Appetite Regulation

The role of dietary fibre (DF) in disease prevention has been extensively investigated and prospective studies observed that increased DF intake decreased the risk of cardiovascular disease (CVD), reduced the risk of weight gain as well as the risk of type 2 diabetes (T2D). Also a diet characterized by low glycaemic index (GI) has been shown to reduce the risk of T2D and CVD. More recently, evidence have accumulated suggesting that obesity, T2D and CVD may stem from a high-fat diet induced metabolic endotoxemia, implicating a role of the composition of gut microbiota. Mechanisms behind observed health merits of DF-rich foods suggests e.g. delayed digestion and absorption or increased gut fermentation of indigestible carbohydrates. The present thesis studies the potential impact of indigestible carbohydrates intrinsic to barley kernel- and legume products on cardiometabolic risk factors and appetite regulation using a semi-acute meal study approach in healthy young or elderly subjects. The work described is based on randomized cross-over studies, and metabolic responses were measured in an over-night perspective, i.e. from evening meal to breakfast. The possible link between gut fermentation of indigestible carbohydrates and metabolic responses was evaluated from analysis of breath hydrogen (H2) and circulating levels of short-chain fatty acids (SCFA). Healthy young subjects were provided a late evening meal with boiled barley kernels (BK) or reference white wheat brad (WWB). At a subsequent breakfast, decreased blood (b-) glucose responses and increased concentrations of plasma (p-) glucagon-like peptide (GLP)-1 were observed after the BK evening meal, compared with WWB. The decreased b-glucose- and increased p-GLP-1 responses were maintained during the experimental day, 10.5-16 hours (h) after intake of the BK evening meal. In addition, decreased voluntary energy intake at a lunch meal consumed approximately 14 h after BK was registered while at the same time promoting decreased subjective ratings of hunger over the entire experimental day (10.5-16 h), compared to after WWB evening meal. Further, higher levels of gut fermentation metabolites, i.e. serum (s-) SCFA, and breath H2, were observed at breakfast after BK evening meal, compared to WWB. Supportive of a link between gut microbial metabolism and appetite regulation, p-GLP-1 levels were positively correlated to s-propionate, and inversely related to subjective feelings of hunger and desire to eat, respectively. The impact of barley kernel based bread (BB) on glycaemia and appetite regulation were evaluated in elderly subjects (50-70 years) after three days intake of BB, as opposed to three days intake of WWB. At a subsequent standardized breakfast on day four, decreased b-glucose- and s-insulin responses were observed, and a measure of insulin sensitivity (ISIcomposite) was improved. The metabolic benefits of BB in an over-night perspective previously observed in young adults (20-35 years) were thus also present among a more mature study cohort (50-70 years). The results are among the first to show that a meal rich in intrinsic indigestible carbohydrates promotes parallel increase in plasma levels of gut-derived hormones p-GLP-1, p-peptide YY (PYY) and p-GLP-2 in healthy humans. This is of potential importance in relation to facilitated glucose- and appetite regulation, as well as reduced sub-clinical inflammation. The increase in p-GLP-2 might be considered beneficial considering its role in maintaining integrity of the intestinal epithelium, in favor of a lowered inflammatory tonus. In addition, three days of BB compared to WWB stimulated gut microbial metabolism as indicated by increased levels of s-SCFA and breath H2. The potential interplay between gut fermentation and host metabolism was supported by a positive correlation between total s-SCFA; and p-GLP-1 or p-PYY, respectively. It was hypothesized that intake of commercially available probiotics could interfere with gut microbiota derived mechanisms for observed benefits of barley kernel products on metabolism and appetite regulation. Healthy young subjects were provided with BB or WWB during a four day intervention. BB intervention was performed twice, once including a dietary background of a mixture of probiotics (BB(+)) and once with placebo (BB(-)). The WWB intervention was performed with placebo background (WWB(-)). At a subsequent standardized breakfast, BB interventions increased p-GLP-1 levels and increased breath H2 both with and without probiotic supplementation, compared to WWB(-). Decreased glycaemic responses were observed after BB(-) but not after BB(+), compared to WWB(-). However, not only p-GLP-2 but also p-glucagon and s-PAI-1 were increased after BB(+) compared to BB(-). It is concluded that with the exception of increased GLP-2 concentrations, overall outcome of the BB intervention was not enhanced by a dietary background of common probiotics; rather, the benefits on glycaemic regulation were to some extent blunted. Legumes, in conformity with barley kernel products, are naturally rich in DF, including RS. However the DF components differ. Thus, legumes are rich in raffinose-oligosaccharides and galactomannans, whereas barley is especially acknowledged for its high content of β-glucans. It was hypothesized that the DF present in legumes could promote gut fermentation and mediate benefits on glucose- and appetite regulation, as previously observed for barley kernel products. Boiled beans of different varieties (red, white, brown and black) or chickpeas were given to healthy young subjects as a late evening meal. WWB was included as a reference evening meal. A late-evening meal of boiled brown beans (BrB) beneficially improved glucose tolerance at a subsequent standardized breakfast, as judged from lowered b-glucose- and s-insulin responses, as compared to WWB evening meal. Having chickpeas in the evening significantly increased perceived feeling of satiety at fasting in the morning compared to WWB evening meal. All legumes increased gut fermentative activity 11-14 h after intake as indicated by increased breath H2. Further, investigations with respect to cardiometabolic risk markers were performed after BrB only. The evening meal with BrB increased insulin sensitivity index (ISIcomposite), increased s-SCFA and promoted higher levels of satiety hormones (p PYY and p-oxyntomodulin (OXM)), reduced the orexigenic peptide ghrelin in plasma and decreased markers of inflammation (s-IL-6 and s-IL-18) in response to the subsequent breakfast, compared with WWB evening meal. Additionally, the BrB evening meal stimulated higher p-GLP-2 in the late postprandial phase at the standardized breakfast. Inverse relations between willingness to eat and p-PYY and p-GLP-2, respectively, were found and supporting a beneficial role of BrB in appetite regulation. In summary, barley kernel- and legume products rich in DF, were found to induce metabolic advantages, as indicated by decreased glycaemia, increased insulin sensitivity, beneficial effects on appetite regulatory hormones and decreased voluntary food intake at subsequent meals. The results are supportive of a mechanism whereby indigestible carbohydrates may be involved in positive health outcomes, with respect to obesity, T2D and CVD, through mechanisms involving fermentation. The results provide interesting possibilities to develop new foods containing specific indigestible carbohydrate substrates capable of addressing the gut microbiota – host metabolism cross-talk.