SCOPE:This study aims to identify the gut enterotypes that explain differential responses to intervention with whole grain rye by proposing an "enterotype - metabolic" model. METHODS AND RESULTS:A 12-week randomized controlled trial is conducted in Chinese adults, with 79 subjects consuming whole grain products with fermented rye bran (FRB) and 77 consuming refined wheat products in this exploratory post-hoc analysis. Responders or non-responders are identified according to whether blood glucose decreased by more than 10% after rye intervention. Compared to non-responders, responders in FRB have higher baseline Bacteroides (p < 0.001), associated with reduced blood glucose (p < 0.001), increased Faecalibacterium (p = 0.020) and Erysipelotrichaceae_UCG.003 (p = 0.022), as well as deceased 7β-hydroxysteroid dehydrogenase (p = 0.033) after intervention. The differentiated gut microbiota and metabolites between responders and non-responders after intervention are enriched in aminoacyl-tRNA biosynthesis. CONCLUSION:The work confirms the previously suggested importance of microbial enterotypes in differential responses to whole grain interventions and supports taking enterotypes into consideration for improved efficacy of whole grain intervention for preventing type 2 diabetes. Altered short-chain fatty acids and bile acid metabolism might be a potential mediator for the beneficial effects of whole grain rye on glucose metabolism.

Prostate cancer (PC) is a common cancer among men, and preventive strategies are warranted. Benzoxazinoids (BXs) in rye have shown potential against PC in vitro but human studies are lacking. The aim was to establish a quantitative method for analysis of BXs and investigate their plasma levels after a whole grain/bran rye vs refined wheat intervention, as well as exploring their association with PSA, in men with PC. A quantitative method for analysis of 22 BXs, including novel metabolites identified by mass spectrometry and NMR, was established, and applied to plasma samples from a randomized crossover study where patients with indolent PC (n = 17) consumed 485 g whole grain rye/rye bran or fiber supplemented refined wheat daily for 6 wk. Most BXs were significantly higher in plasma after rye (0.3–19.4 nmol/L in plasma) vs. refined wheat (0.05–2.9 nmol/L) intake. HBOA-glc, 2-HHPAA, HBOA-glcA, 2-HPAA-glcA were inversely correlated to PSA in plasma ( p < 0.04). To conclude, BXs in plasma, including metabolites not previously analyzed, were quantified. BX metabolites were significantly higher after rye vs refined wheat consumption. Four BX-related metabolites were inversely associated with PSA, which merits further investigation.

Rye is among the cereals with the highest content of dietary fibre. A high rye food intake has been associated with improved metabolic risk factors in some but not all observational and intervention studies. Whole-grain rye has also been suggested to affect the gut microbiota in individuals with metabolic syndrome. However, it is yet unclear to what extent effects on the gut microbiota mediate the beneficial metabolic responses of whole-grain rye intake. We hypothesized that a high intake of whole grain rye products containing fermented rye bran (FRB) vs. refined wheat based products (RW) could alter the gut microbiota and short-chain fatty acid (SCFA) composition towards a phenotype associated with beneficial metabolic effects in a population not used to such foods. For this purpose, we conducted a post hoc analysis of a 12-week randomized controlled trial in Chinese adults with Helicobacter pylori (HP) infection, with 53 participants consuming RW and 31 participants consuming FRB included in the analysis. Anthropometric measurements and fasting blood and fecal sample analyses as well as 13C-urea breath test were performed at baseline and after a 12-week intervention. At week 12, we observed a higher serum insulin concentration (P-value = 0.038) in the FRB group (n = 31) versus the RW group (n = 53), and this difference was corroborated with alterations in the genus-level relative abundances of the gut microbiota, represented by an increase in Romboutsia and a reduction in Bilophila in the FRB group (n = 22) versus the RW group (n = 46). Compared to the RW group (n = 53), fecal acetic acid concentration was significantly higher in the FRB group (n = 31) at week 12. We also found that fecal acetic and butyric acids positively, while isobutyric, isovaleric and 2-methylbutyric acids inversely, correlated with the gut Romboutsia level among all participants (n = 68) at week 12. We found positive correlations of fecal isobutyric, isovaleric and 2-methylbutyric acids with gut Bilophila (n = 68). In conclusion, our results suggest that the intake of high-fibre rye products could modify gut Romboutsia and Bilophila in a Chinese population with HP infection. These effects are paralleled with favorable modifications of the SCFA concentration and are associated with altered glycemic traits.

Background: High dietary fiber intake has been associated with reduced risk of Helicobacter pylori infection and co-morbidities such as gastric cancer but also with reduced risk of cardiovascular disease. It has been suggested that fermented rye could affect Helicobacter pylori bacterial load and that high- fiber rye may be superior to wheat for improvement of several cardiometabolic risk factors, but few long-term interventions with high fiber rye foods have been conducted. Objective: To examine the effect of high-fiber wholegrain rye foods with added fermented rye bran vs. refined wheat on Helicobacter pylori infection and cardiometabolic risk markers in a Chinese population with a low habitual consumption of high fiber cereal foods. Design: A parallel dietary intervention was set up and 182 normal- or overweight men and women were randomized to consume wholegrain rye products containing fermented rye bran (FRB) or refined wheat (RW) for 12 weeks. Anthropometric measurements, fasting blood sample collection and 13C-urea breath test (13C-UBT) were performed at baseline and after 6 and 12 weeks of intervention as well as 12 weeks after the end of the intervention. Results: No difference between diets on Helicobacter pylori bacterial load measured by 13C-UBT breath test or in virulence factors of Helicobacter pylori in blood samples were found. Low density lipoprotein cholesterol (LDL-C) and high sensitivity C-reactive protein (hs-CRP) were significantly lower in the FRB group, compared to the RW group after 12 weeks of intervention. The intervention diets did not affect markers of glucose metabolism or insulin sensitivity. Conclusions: While the results of the present study did not support any effect of FRB on Helicobacter pylori bacterial load, beneficial effects on LDL-C and hs-CRP were clearly shown. This suggest that consumption of high fiber rye foods instead of refined wheat could be one strategy for primary prevention of cardiovascular disease. Clinical Trial Registration: The trial was registered at www.clinicaltrials.gov, Identifier: NCT03103386.

Background & aims: Rye consumption has shown beneficial effects on prostate cancer tumors, as indicated by slower initial tumor growth in animal models and lowering of prostate-specific antigen (PSA) in humans. This study evaluated the effects of whole grain/bran rye consumption on low-grade inflammation and endothelial function biomarkers in men with prostate cancer. Methods: Seventeen men with untreated, low-grade prostate cancer consumed 485 g rye whole grain and bran products (RP) per day or refined wheat products with added cellulose (WP) in a randomized crossover design. Fasting blood samples were taken before and after 2, 4, and 6 weeks of treatment. Results: Concentrations of tumor nuclear factor-receptor 2 (TNF-R2), e-selectin, and endostatin were significantly lower after consumption of the RP diet compared with WP (p < 0.05). Cathepsin S concentration was positively correlated to TNF-R2 and endostatin concentrations across all occasions. Strong correlations were consistently found between intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) and between interleukin-6 (IL-6) and interleukin-1 receptor antagonist (IL-1RA). No effect of intervention was found in 92 inflammation-related protein biomarkers measured in a proximity extension assay. Conclusions: RP diet lowered TNF-R2, e-selectin, and endostatin, compared with WP in men with prostate cancer. These effects were accompanied by a reduction in PSA. (C) 2019 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Background Plant and animal breeding can contribute to promote human health by providing new and healthier food products that farmers can produce in an economically viable way and consumers will choose to buy and eat. However, this can only be achieved if breeding makes full use of knowledge about nutrition, consumer behaviour, farming and agricultural economics, A strategy is needed for breeding for public health. Scope and Approach: A multidisciplinary group of researchers has developed a strategy for plant and animal breeding for public health. The group includes experts in plant breeding, animal breeding, food science, nutrition science, clinical nutrition, agricultural economics, consumer research, and ethics. Key Findings and Conclusions: An outline is proposed of a strategy for breeding for public health. It aims at improving public health in both low- and high-income countries. To prevent chronic disease, the highest priority should be to develop healthy variants of traditional food items that can be introduced universally, i.e. completely replace the older, less healthy variants. In particular in low-income countries, food products with enhanced micronutrient content are urgently needed. In all countries, crops with improved fatty acid composition can contribute substantially to improved public health. A reasonable second priority is products that may not be suitable for universal introduction but will expectedly be demanded by large groups of consumers. One example could be diminishing the energy density of traditional foodstuffs by reducing their fat, sugar, and starch content and increasing their dietary fibre content, Changes in the current organization of the market for farm products are needed to encourage the production of healthier foodstuffs.

Sequential carbohydrate synthesis is important for plant survival because it guarantees energy supplies for growth and development during plant ontogeny and reproduction. Starch and fructan are two important carbohydrates in many flowering plants and in human diets. Understanding this coordinated starch and fructan synthesis and unraveling how plants allocate photosynthates and prioritize different carbohydrate synthesis for survival could lead to improvements to cereals in agriculture for the purposes of greater food security and production quality. Here, we report a system from a single gene in barley employing two alternative promoters, one intronic/exonic, to generate two sequence-overlapping but functionally opposing transcription factors, in sensing sucrose, potentially via sucrose/glucose/fructose/trehalose 6-phosphate signaling. The system employs an autoregulatory mechanism in perceiving a sucrose-controlled trans activity on one promoter and orchestrating the coordinated starch and fructan synthesis by competitive transcription factor binding on the other promoter. As a case in point for the physiological roles of the system, we have demonstrated that this multitasking system can be exploited in breeding barley with tailored amounts of fructan to produce healthy food ingredients. The identification of an intron/exon-spanning promoter in a hosting gene, resulting in proteins with distinct functions, adds to the complexity of plant genomes.

Since the 1970s, the positive effects of dietary fiber on health have increasingly been recognized. The collective term "dietary fiber" groups structures that have different physiologic effects. Since 1995, some dietary fibers have been denoted as prebiotics, implying a beneficial physiologic effect related to increasing numbers or activity of the gastrointestinal microbiota. Given the complex composition of the microbiota, the demonstration of such beneficial effects is difficult. In contrast, an exploration of the metabolites of dietary fiber formed as a result of its fermentation in the colon offers better perspectives for providing mechanistic links between fiber intake and health benefits. Positive outcomes of such studies hold the promise that claims describing specific health benefits can be granted. This would help bridge the "fiber gap"-that is, the considerable difference between recommended and actual fiber intakes by the average consumer.

Barley spikes of the cultivars/breeding lines Gustav, Karmosé and SLU 7 were harvested at 9, 12 and 24 days after flowering in order to study starch structure in developing barley endosperm. Kernel dry weight, starch content and amylose content increased during development. Structural analysis was performed on whole starch and included the chain-length distribution of the whole starches and their β-limit dextrins. Karmosé, possessing the amo1 mutation, had higher amylose content and a lower proportion of long chains (DP ≥38) in the amylopectin component than SLU 7 and Gustav. Structural differences during endosperm development were seen as a decrease in molar proportion of chains of DP 22-37 in whole starch. In β-limit dextrins, the proportion of Bfp-chains (DP 4-7) increased and the proportion of BSmajor-chains (DP 15-27) decreased during development, suggesting more frequent activity of starch branching enzymes at later stages of maturation, resulting in amylopectin with denser structure.

Amylopectin fine structure and starch gelatinization and retrogradation were studied in 10 different barley cultivars/breeding lines. Clusters and building blocks were isolated from the amylopectin by α-amylase from Bacillus amyloliquefaciens and their structure was characterized. Gelatinization was studied at a starch:water ratio of 1:3, and retrogradation was studied on gelatinized starch at starch:water ratio of 1:2, by differential scanning calorimetry. Three barley cultivars/breeding lines possessed the amo1 mutation, and they all had a lower molar proportion of chains of DP ≥38 and more of large building blocks. The amo1 mutation also resulted in a higher gelatinization temperature and a broader temperature interval during gelatinization. Overall, small clusters with a dense structure resulted in a higher gelatinization temperature while retrogradation was promoted by short chains in the amylopectin and many large building blocks.

Fructans are important in the survival of plants and also valuable for humans as potentially health promoting food ingredients. In this study fructan content and composition were determined in grains of 20 barley breeding lines and cultivars with a wide variation in chemical composition, morphology and country of origin, grown at one site in Chile. There was significant genotypic variation in grain fructan content ranging from 0.9% to 4.2% of grain dry weight. Fructan degree of polymerisation (DP) was analysed using high-performance anion-exchange chromatography with pulsed amperometric detection (HPAEC-PAD). Changes in the distribution of different chain lengths and the pattern of structures of fructan were detected with increasing amount of fructan in the different barleys. A positive correlation was found between fructan content and the relative amount of long chain fructan (DP > 9) (r = 0.54, p = 0.021). Our results provide a basis for selecting promising barley lines and cultivars for further research on fructan in barley breeding with the aim to produce healthy food products.

Whole-grain intake has been reported to be associated with a lower risk of several lifestyle-related diseases such as type 2 diabetes, CVD and some types of cancers. As measurement errors in self-reported whole-grain intake assessments can be substantial, dietary biomarkers are relevant to be used as complementary tools for dietary intake assessment. Alkylresorcinols (AR) are phenolic lipids found almost exclusively in whole-grain wheat and rye products among the commonly consumed foods and are considered as valid biomarkers of the intake of these products. In the present study, we analysed the plasma concentrations of five AR homologues in 2845 participants from ten European countries from a nested case-control study in the European Prospective Investigation into Cancer and Nutrition. High concentrations of plasma total AR were found in participants from Scandinavia and Central Europe and lower concentrations in those from the Mediterranean countries. The geometric mean plasma total AR concentrations were between 35 and 41 nmol/l in samples drawn from fasting participants in the Central European and Scandinavian countries and below 23 nmol/l in those of participants from the Mediterranean countries. The whole-grain source (wheat or rye) could be determined using the ratio of two of the homologues. The main source was wheat in Greece, Italy, the Netherlands and the UK, whereas rye was also consumed in considerable amounts in Germany, Denmark and Sweden. The present study demonstrates a considerable variation in the plasma concentrations of total AR and concentrations of AR homologues across ten European countries, reflecting both quantitative and qualitative differences in the intake of whole-grain wheat and rye.

Alkylresorcinols (AR) with alkyl chains in the range of C15 to C25 are phenolic lipids particularly abundant in the outer parts of wheat and rye kernels and in food products containing these parts. The content in whole grain and bran products is high (200–4000 μg/g), whereas only trace-levels are detected in refined products. Alkylresorcinols are absorbed in humans in proportion to intake and have therefore been suggested and evaluated as biomarkers for whole grain wheat and rye intake. In humans, plasma AR concentrations reach micromolar concentrations immediately after whole grain wheat and rye product consumption and nano-molar levels at fasting conditions. Results from different model studies have indicated that AR may have some bioactivities including enzyme inhibition, suppression of adipocyte lipolysis and inhibition of colon cancer tumor growth but it is currently unknown whether AR bioactive in vivo or not. This chapter details the recent research findings on alkylresorcinols with emphasis on their occurrence, bioavailability, bioactivity and utility as biomarkers.