Whole grain cereal products and baseline gut microbiota composition in metabolic and appetite regulation in healthy humans Emphasizing rye and barley

The prevalence of obesity, type 2 diabetes (T2D) and cardiovascular disease (CVD) is increasing continuously worldwide. These metabolic diseases are associated with many health issues, including increased risk of depression and cognitive impairment. Whole grain (WG) has shown potential to prevent obesity, T2D and CVD. One mechanism can be related to gut fermentation of specific indigestible carbohydrates, i.e. dietary fiber (DF). The aim of this thesis was to investigate the relationship between gut fermentation of DF, and systemic effects including cardiometabolic risk markers and appetite regulation in healthy subjects. The thesis focuses on the potential prebiotic substrates in rye kernel and flour-based products, and the possible enhanced metabolic effects of adding commercial resistant starch (RS2) to rye flour. The thesis also undertook to evaluate effects of rye prebiotics on cognitive functions and/or mood. Furthermore, the impact of barley kernel products on metabolic regulation was studied in relation to gut abundance and ratios of Prevotella and Bacteroides. The thesis is based on four interventional studies with randomized crossover design, including healthy subjects of different ages (20– 30 or 50–70 years). WG rye breads (based on kernels or WG rye flour or a WG rye kernel and flour mixture) or barley kernel-based breads, rich in DF, were provided as late evening meals. In addition, RS2 was added to some WG rye flour-based breads to substitute RS lost during the milling process. White wheat bread (WWB) was used as reference evening meal. In all studies, the subjects consumed the final portion of the test product in the evening (based on 50 g available carbohydrates), after which test variables were measured the next morning at fasting and following a standardized breakfast, i.e. 11–14 hours after ingestion of the test products. In Paper I, a WG rye kernel-based (RKB) evening meal decreased the incremental glucose and insulin areas, and increased the appetite and glucose regulatory gut hormones GLP-1 and PYY, in young adults at a subsequent breakfast, compared to WWB. Furthermore, RKB increased total fasting SCFA (acetate, propionate and butyrate) concentrations and breath H2 excretions the following day. In Paper II, effects on glucose, insulin and PYY concentrations could be further enhanced, in young adults, by replacing part of the rye kernels with WG rye flour and RS2. In Paper III, studies in middle-aged subjects showed that the WG rye mixture, in addition to its benefits on insulin sensitivity and PYY levels also increased GLP-2 concentrations, indicative of a beneficial effect on gut barrier function. This product also improved mood and increased feelings of happiness and wakefulness, compared to WWB. In Paper IV, the metabolic impact of a barley kernel product was studied in middle-aged subjects. The subjects were divided into different groups depending on gut Prevotella/Bacteroides ratio at baseline prior to the intervention. The results showed that the metabolic regulation differed between the test subjects depending on the baseline gut microbiota composition. Consequently, it was observed that a higher ratio of Prevotella/Bacteroides favored lower insulin response and inflammatory tone and subjective appetite ratings. In summary, this thesis shows that WG rye products (rye kernel-based solely or blended with WG rye flour and RS2), may positively affect glucose and appetite regulation 11–14 h post ingestion. In addition, mood was improved post intake of the WG rye blend. The results indicate a prebiotic mechanism mediated via gut fermentation of DF in the WG rye breads. The studies also suggest that the metabolic regulation may be affected differently depending on gut microbiota composition. It is concluded that kernel-based rye or barley products as well as a blend of WG rye kernels/flour with RS have an anti-diabetic and anti-obesogenic potential.