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Abstract Background Although insulin resistance (IR) is among the most frequent and pathogenically relevant complications accompanying childhood obesity, its role in modulating and exacerbating obesity pathophysiology has not yet been completely clarified. Methods To get deeper insights into the interplay between childhood obesity and IR, we leveraged a comprehensive experimental design based on a combination of observational data, in vivo challenge tests (i.e., oral glucose tolerance test), and ex vivo assays (i.e., incubation of erythrocytes with insulin) using a population comprising children with obesity and IR, children with obesity without IR, and healthy controls, from whom plasma and erythrocyte samples were collected for subsequent metabolomics analysis. Results Children with concomitant IR showed exacerbated metabolic disturbances in the crosstalk between endogenous, microbial, and environmental determinants, including failures in energy homeostasis, amino acid metabolism, oxidative stress, synthesis of steroid hormones and bile acids, membrane lipid composition, as well as differences in exposome-related metabolites associated with diet, exposure to endocrine disruptors, and gut microbiota. Furthermore, challenge tests and ex vivo assays revealed a deleterious impact of IR on individuals’ metabolic flexibility, as reflected in blunted capacity to regulate homeostasis in response to hyperinsulinemia, at both systemic and erythroid levels. Conclusions Thus, we have demonstrated for the first time that metabolite alterations in erythrocytes represent reliable and sensitive biomarkers to disentangle the metabolic complexity of IR and childhood obesity. This study emphasizes the crucial need of addressing inter-individual variability factors, such as the presence of comorbidities, to obtain a more accurate understanding of obesity-related molecular mechanisms.

Abstract Background Insulin resistance is a frequent precursor of typical obesity and metabolic syndrome complications. However, accurate diagnosis remains elusive because of its pathophysiological complexity and heterogeneity. Herein, we have explored the utility of insulin secretion dynamics in response to an oral glucose tolerance test as a surrogate marker to identify distinct metabotypes of disease severity. Methods The study population consisted of children with obesity and insulin resistance, stratified according to the post-challenge insulin peak timing (i.e., early, middle, and late peak), from whom fasting and postprandial plasma and erythrocytes were collected for metabolomics analysis. Results Children with late insulin peak manifested worse cardiometabolic health (i.e., higher blood pressure, glycemia, and HOMA-IR scores) than early responders. These subjects also showed more pronounced changes in metabolites mirroring failures in energy homeostasis, oxidative stress, metabolism of cholesterol and phospholipids, and adherence to unhealthy dietary habits. Furthermore, delayed insulin peak was associated with impaired metabolic flexibility, as reflected in compromised capacity to regulate mitochondrial energy pathways and the antioxidant defense in response to glucose overload. Conclusions Altogether, these findings suggest that insulin resistance could encompass several phenotypic subtypes characterized by graded disturbances in distinctive metabolic derangements occurring in childhood obesity, which serve as severity predictive markers.

Abstract We investigated data-driven and hypothesis-driven dietary patterns and their association to plasma metabolite profiles and subsequent colorectal cancer (CRC) risk in 680 CRC cases and individually matched controls. Dietary patterns were identified from combined exploratory/confirmatory factor analysis. We assessed association to LC–MS metabolic profiles by random forest regression and to CRC risk by multivariable conditional logistic regression. Principal component analysis was used on metabolite features selected to reflect dietary exposures. Component scores were associated to CRC risk and dietary exposures using partial Spearman correlation. We identified 12 data-driven dietary patterns, of which a breakfast food pattern showed an inverse association with CRC risk (OR per standard deviation increase 0.89, 95% CI 0.80–1.00, p = 0.04). This pattern was also inversely associated with risk of distal colon cancer (0.75, 0.61–0.96, p = 0.01) and was more pronounced in women (0.69, 0.49–0.96, p = 0.03). Associations between meat, fast-food, fruit soup/rice patterns and CRC risk were modified by tumor location in women. Alcohol as well as fruit and vegetables associated with metabolite profiles (Q2 0.22 and 0.26, respectively). One metabolite reflecting alcohol intake associated with increased CRC risk, whereas three metabolites reflecting fiber, wholegrain, and fruit and vegetables associated with decreased CRC risk.

MotivationIn the field of precision nutrition, predicting metabolic response to diet and identifying groups of differential responders are two highly desirable steps toward developing tailored dietary strategies. However, data analysis tools are currently lacking, especially for complex settings such as crossover studies with repeated measures.Current methods of analysis often rely on matrix or tensor decompositions, which are well suited for identifying differential responders but lacking in predictive power, or on dynamical systems modeling, which may be used for prediction but typically requires detailed mechanistic knowledge of the system under study. To remedy these shortcomings, we explored dynamic mode decomposition (DMD), which is a recent, data-driven method for deriving low-rank linear dynamical systems from high dimensional data.Combining the two recent developments “parametric DMD” (pDMD) and “DMD with control” (DMDc) enabled us to (i) integrate multiple dietary challenges, (ii) predict the dynamic response in all measured metabolites to new diets from only the metabolite baseline and dietary input, and (iii) identify inter-individual metabolic differences, i.e., metabotypes. To our knowledge, this is the first time DMD has been applied to analyze time-resolved metabolomics data.ResultsWe demonstrate the potential of pDMDc in a crossover study setting. We could predict the metabolite response to unseen dietary exposures on both measured (R2 = 0.40) and simulated data of increasing size (Rmax2= 0.65), as well as recover clusters of dynamic metabolite responses. We conclude that this method has potential for applications in personalized nutrition and could be useful in guiding metabolite response to target levels.Availability and implementationThe measured data analyzed in this study can be provided upon reasonable request. The simulated data along with a MATLAB implementation of pDMDc is available at https://github.com/FraunhoferChalmersCentre/pDMDc.

BackgroundIn the ADIRA (Anti-inflammatory Diet In Rheumatoid arthritis) trial, compliance to the study diets has previously been described primarily with a score based on reported intake of trial foods from telephone interviews. The aim of this study was to evaluate compliance using objective dietary biomarkers for whole grain, fruit and vegetables, margarine and oil, seafood and overall fat quality, as well as reported intake from food records of key components of the study diets.MethodsFifty patients with rheumatoid arthritis were randomized to begin with the intervention diet (rich in whole grain, fruit and vegetables, margarine/oil and seafood) or the control diet (rich in meat and high-fat dairy) for 10 weeks, followed by a ~ 4 months wash-out period, and then switched diet. Compliance was evaluated using plasma alkylresorcinols (AR) as biomarkers for intake of whole grain wheat and rye, serum carotenoids for fruit and vegetables, plasma linoleic acid (LA, 18:2 n-6) and -α-linolenic acid (18:3, n-3) for margarine and cooking oil, plasma eicosapentaenoic acid (EPA, 20:5 n-3), −docosahexaenoic acid (DHA 22:6, n-3) and -docosapentaenoic acid (22:5 n-3) for seafood, and plasma fatty acid pattern for the overall dietary fat quality. Reported intake of whole grain, fruit, berries and vegetables, seafood, red meat, and fat quality was extracted from 3-d food records.ResultsPlasma AR C21:0 and C23:0, LA, EPA, and DHA were higher while total serum carotenoids were lower after the intervention diet period compared to the control diet period (AR and carotenoids: p =

Abstract Dietary whole grain consumption has been postulated to have metabolic benefits. The purpose of this study was to compare a pregnancy diet containing 75% of total carbohydrates as refined grains with a diet of 75% of total carbohydrates as whole grains for pregnancy outcomes and effects on the microbiome. Gestational weight gain, glucose tolerance and newborn outcomes were measured on 248 enrolled compliant women from whom a subset of 103 women consented to give 108 vaginal and 109 anal swabs. The data presented here are limited to the patients from whom the vaginal and anal swabs were obtained in order to study the microbiome. A microbiome—16SrRNA survey—was characterized in these samples. Samples and measurements were obtained at the first obstetrical visit, before beginning a prescribed diet (T1—baseline) and after 17–32 weeks on the prescribed diet (T3). Food frequency questionnaires and total plasma alkylresorcinols were used as a measure of whole grain consumption. There were no dietary differences in maternal weight gain, birth weight, or glucose tolerance test. Mothers consuming the whole grains diet showed a trend of gestational decrease in vaginal bacterial alpha diversity, with increasing Lactobacillus-dominance. No significant difference was observed for the anal microbiome. The results suggest that diet modulations of the vaginal microbiome during gestation may have important implications for maternal and neonatal health and in the intergenerational transfer of maternal microbiome. Trial registration: ClinicalTrials.gov Identifier: NCT03232762.

Abstract 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

The global prevalence of type 2 diabetes mellitus (T2DM) has surged in recent decades, and the identification of differential glycemic responders can aid tailored treatment for the prevention of prediabetes and T2DM. A mixed meal tolerance test (MMTT) based on regular foods offers the potential to uncover differential responders in dynamical postprandial events. We aimed to fit a simple mathematical model on dynamic postprandial glucose data from repeated MMTTs among participants with elevated T2DM risk to identify response clusters and investigate their association with T2DM risk factors and gut microbiota. Data were used from a 12-week multi-center dietary intervention trial involving high-risk T2DM adults, comparing high- versus low-glycemic index foods within a Mediterranean diet context (MEDGICarb). Model-based analysis of MMTTs from 155 participants (81 females and 74 males) revealed two distinct plasma glucose response clusters that were associated with baseline gut microbiota. Cluster A, inversely associated with HbA1c and waist circumference and directly with insulin sensitivity, exhibited a contrasting profile to cluster B. Findings imply that a standardized breakfast MMTT using regular foods could effectively distinguish non-diabetic individuals at varying risk levels for T2DM using a simple mechanistic model.

Fermentation has long been utilized to preserve and enhance the flavor and nutritional value of foods. Recently, fermented foods have gained popularity, reaching new consumer groups due to perceived health benefits. However, the microbial composition of many fermented foods re-mains unknown. Here, we characterized the bacterial composition, diversity, and richness of 47 fermented foods available in Sweden, including kombucha, water kefir, milk kefir, yogurt, plant-based yogurt alternatives, kimchi, sauerkraut, and fermented vegetables. Via 16S rRNA gene sequencing, we identified 2497 bacteria (amplicon sequence variants). The bacterial composition was strongly associated with the type of fermented food, and lactic acid bacteria and/or acetic acid bacteria dominated most samples. However, each fermented food had a unique composition, with kombucha and water kefir having the highest diversity across and within samples. Few bacteria were abundant in multiple foods and food groups. These were Streptococcus thermophilus in yogurts and plant-based yoghurts; Lactococcus lactis in milk kefirs and one water kefir; and Lactiplantibacillus plantarum in kimchi, sauerkraut, and fermented cucumber. The broad range of fermented foods included in this study and their diverse bacterial communities warrant further investigation into the implications of microbial compositions for product traits and potential impact on human health.

Abstract Tail biting is an abnormal behaviour that causes stress, injury and pain. Given the critical role of the gut-microbiota in the development of behavioural problems in humans and animals, the aim of this study was to determine whether pigs that are biters, victims of tail biting or controls (nine matched sets of pigs) have a different microbiota composition, diversity and microbial metabolite profile. We collected faecal and blood samples from each individual for analysis. The gut microbiota composition was most different between the biter and the control pigs, with a higher relative abundance of Firmicutes in tail biter pigs than the controls. Furthermore, we detected differences in faecal and plasma short chain fatty acids (SCFA) profiles between the biter and victim pigs, suggesting physiological differences even though they are kept in the same pen. Thus, in addition to supporting an association between the gut microbiota and tail biting in pigs, this study also provides the first evidence of an association between tail biting and SCFA. Therefore, further research is needed to confirm these associations, to determine causality and to study how the SCFA profiles of an individual play a role in the development of tail biting behaviour.

Abstract Background Colorectal cancer (CRC) screening reduces CRC incidence and mortality. However, current screening methods are either hampered by invasiveness or suboptimal performance, limiting their effectiveness as primary screening methods. To aid in the development of a non-invasive screening test with improved sensitivity and specificity, we have initiated a prospective biomarker study (CRCbiome), nested within a large randomized CRC screening trial in Norway. We aim to develop a microbiome-based classification algorithm to identify advanced colorectal lesions in screening participants testing positive for an immunochemical fecal occult blood test (FIT). We will also examine interactions with host factors, diet, lifestyle and prescription drugs. The prospective nature of the study also enables the analysis of changes in the gut microbiome following the removal of precancerous lesions. Methods The CRCbiome study recruits participants enrolled in the Bowel Cancer Screening in Norway (BCSN) study, a randomized trial initiated in 2012 comparing once-only sigmoidoscopy to repeated biennial FIT, where women and men aged 50–74 years at study entry are invited to participate. Since 2017, participants randomized to FIT screening with a positive test result have been invited to join the CRCbiome study. Self-reported diet, lifestyle and demographic data are collected prior to colonoscopy after the positive FIT-test (baseline). Screening data, including colonoscopy findings are obtained from the BCSN database. Fecal samples for gut microbiome analyses are collected both before and 2 and 12 months after colonoscopy. Samples are analyzed using metagenome sequencing, with taxonomy profiles, and gene and pathway content as primary measures. CRCbiome data will also be linked to national registries to obtain information on prescription histories and cancer relevant outcomes occurring during the 10 year follow-up period. Discussion The CRCbiome study will increase our understanding of how the gut microbiome, in combination with lifestyle and environmental factors, influences the early stages of colorectal carcinogenesis. This knowledge will be crucial to develop microbiome-based screening tools for CRC. By evaluating biomarker performance in a screening setting, using samples from the target population, the generalizability of the findings to future screening cohorts is likely to be high. Trial registration ClinicalTrials.gov Identifier: NCT01538550 .

Introduction In 2012, the estimated global prevalence of pre-diabetes was 280 million, and the prevalence is expected to rise to 400 million by 2030. Oat-based foods are a good source of beta-glucans, which have been shown to lower postprandial blood glucose. Studies to evaluate the effectiveness of the long-term intake of beta-glucan-enriched bread as part of a habitual diet among individuals with pre-diabetes are needed. Therefore, we designed a multicentre intervention study in adults with pre-diabetes to investigate the effects of consumption of an oat-derived beta-glucan-enriched bread as part of a normal diet on glycated haemoglobin (HbA1c) in comparison to consumption of whole-grain wheat bread.Methods and analysis The CarbHealth trial is a multicentre double-blind randomised controlled 16-week dietary intervention trial in participants 40–70 years of age with a body mass index of ≥27 kg/m2 and HbA1c of 35–50 mmol/mol. The study is conducted at four universities located in Norway, Sweden and Germany and uses intervention breads specifically designed for the trial by Nofima AS. The aim is to recruit 250 participants. The primary outcome is the difference in HbA1c between the intervention and the control groups. The main analysis will include intervention group, study centre and baseline HbA1c as independent variables in an analysis of covariance model.Ethics and dissemination The study protocol was approved by respective ethical authorities in participating countries. The results of the study will be communicated through publication in international scientific journals and presentations at (inter)national conferences.Trial registration number NCT04994327.

Recent studies suggest that a diet rich in sugars significantly affects the gut microbiota. Adverse metabolic effects of sugars may partly be mediated by alterations of gut microbiota and gut health parameters, but experimental evidence is lacking. Therefore, we investigated the effects of high intake of fructose or galactose, with/without fructooligosaccharides (FOS), on gut microbiota composition in rats and explored the association between gut microbiota and low-grade systemic inflammation. Sprague–Dawley rats (n = 6/group) were fed the following isocaloric diets for 12 weeks (% of the dry weight of the sugars or FOS): (1) starch (control), (2) fructose (50%), (3) galactose (50%), (4) starch+FOS (15%) (FOS control), (5) fructose (50%)+FOS (15%), (6) galactose (50%)+FOS (15%), and (7) starch+olive (negative control). Microbiota composition in the large intestinal content was determined by sequencing amplicons from the 16S rRNA gene; 341F and 805R primers were used to generate amplicons from the V3 and V4 regions. Actinobacteria, Verrucomicrobia, Tenericutes, and Cyanobacteria composition differed between diets. Bifidobacterium was significantly higher in all diet groups where FOS was included. Modest associations between gut microbiota and metabolic factors as well as with gut permeability markers were observed, but no associations between gut microbiota and inflammation markers were observed. We found no coherent effect of galactose or fructose on gut microbiota composition. Added FOS increased Bifidobacterium but did not mitigate potential adverse metabolic effects induced by the sugars. However, gut microbiota composition was associated with several metabolic factors and gut permeability markers which warrant further investigations.

Background: A mechanistic understanding of the effects of dietary treatment in irritable bowel syndrome (IBS) is lacking. Our aim was therefore to investigate how fermentable oligo- di-, monosaccharides, and polyols (FODMAPs) and gluten affected gut microbiota and circulating metabolite profiles, as well as to investigate potential links between gut microbiota, metabolites, and IBS symptoms. Methods: We used data from a double-blind, randomized, crossover study with week-long provocations of FODMAPs, gluten, and placebo in participants with IBS. To study the effects of the provocations on fecal microbiota, fecal and plasma short-chain fatty acids, the untargeted plasma metabolome, and IBS symptoms, we used Random Forest, linear mixed model and Spearman correlation analysis. Results: FODMAPs increased fecal saccharolytic bacteria, plasma phenolic-derived metabolites, 3-indolepropionate, and decreased isobutyrate and bile acids. Gluten decreased fecal isovalerate and altered carnitine derivatives, CoA, and fatty acids in plasma. For FODMAPs, modest correlations were observed between microbiota and phenolic-derived metabolites and 3-indolepropionate, previously associated with improved metabolic health, and reduced inflammation. Correlations between molecular data and IBS symptoms were weak. Conclusions: FODMAPs, but not gluten, altered microbiota composition and correlated with phenolic-derived metabolites and 3-indolepropionate, with only weak associations with IBS symptoms. Thus, the minor effect of FODMAPs on IBS symptoms must be weighed against the effect on microbiota and metabolites related to positive health factors.

Background: Accurate assessment of self-reported appetite under free-living conditions is warranted to conduct large-scale intervention studies measuring appetite at a feasible cost. However, the performance of visual analogue scales (VASs) for this purpose has not been widely examined. Method: This randomized crossover trial was conducted to evaluate VASs in free-living vs. clinic-based settings and to assess appetite response following hypocaloric whole-grain rye and refined wheat diets. Twenty-nine healthy adults with overweight or obesity continuously answered VAS questions about their perceived appetite from morning to evening. Results: No differences in whole-day VAS scores (primary outcome) between clinic-based and free-living settings were observed, whereas measures of total area under the curve (tAUC) showed increased fullness in clinic-based interventions of 7% (p < 0.008) for whole-day responses and 13% (p < 0.03) following a snack. Appetite responses for a whole day did not differ between diets whereas rye-based dinners induced 12% (p < 0.016) higher fullness and reduced hunger by 17% (p < 0.02) irrespective of setting. A reduction in hunger of 15% (p < 0.05) was also observed following rye-based vs. wheat-based lunches. Conclusion: The results suggest that the VAS is valid for evaluation of appetite responses between diets under free-living conditions. No difference in self-reported appetite over the whole day was found after whole-grain rye vs. refined wheat-based diets, but there were some suggested differences at certain postprandial periods, in individuals with overweight or obesity.

The food frequency questionnaire (FFQ) is designed to capture an individual’s habitual dietary intake and is the most applied method in nutritional epidemiology. Our aim was to assess the relative validity and reproducibility of the FFQ used in the Diet, Cancer, and Health—Next Generations cohort (DCH-NG). We included 415 Danish women and men aged 18–67 years. Spearman’s correlations coefficients, Bland–Altman limits of agreement and cross-classification between dietary intakes estimated from the FFQ administered at baseline (FFQbaseline), and the mean of three 24-h dietary recalls (24-HDRs) and the FFQ administered after 12 months (FFQ12 months) were determined. Nutrient intakes were energy-adjusted by Nutrient Density and Residual methods. Correlation coefficients ranged from 0.18–0.58 for energy and energy-adjusted nutrient intakes, and the percentage of participants classified into the same quartile ranged from 28–47% between the FFQbaseline and the 24-HDRs. For the FFQ12 months compared with FFQbaseline, correlation coefficients ranged from 0.52–0.88 for intakes of energy, energy-adjusted nutrients, and food groups, and the proportion of participants classified into the same quartiles ranged from 43–69%. Overall, the FFQ provided a satisfactory ranking of individuals according to energy, nutrient, and food group intakes, making the FFQ suitable for use in epidemiological studies investigating diet in relation to disease outcomes.

Abstract Background Bilberries from Sweden, rich in polyphenols, have shown cholesterol-lowering effects in small studies, and the cholesterol-lowering properties of oats, with abundant beta-glucans and potentially bioactive phytochemicals, are well established. Both may provide cardiometabolic benefits following acute myocardial infarction (AMI), but large studies of adequate statistical power and appropriate duration are needed to confirm clinically relevant treatment effects. No previous study has evaluated the potential additive or synergistic effects of bilberry combined with oats on cardiometabolic risk factors. Our primary objective is to assess cardioprotective effects of diet supplementation with dried bilberry or with bioprocessed oat bran, with a secondary explorative objective of assessing their combination, compared with a neutral isocaloric reference supplement, initiated within 5 days following percutaneous coronary intervention (PCI) for AMI. Methods The effects of Bilberry and Oat intake on lipids, inflammation and exercise capacity after Acute Myocardial Infarction (BIOAMI) trial is a double-blind, randomized, placebo-controlled clinical trial. A total of 900 patients will be randomized post-PCI to one of four dietary intervention arms. After randomization, subjects will receive beverages with bilberry powder (active), beverages with high-fiber bioprocessed oat bran (active), beverages with bilberry and oats combined (active), or reference beverages containing no active bilberry or active oats, for consumption twice daily during a 3-month intervention. The primary endpoint is the difference in LDL cholesterol change between the intervention groups after 3 months. The major secondary endpoint is exercise capacity at 3 months. Other secondary endpoints include plasma concentrations of biochemical markers of inflammation, metabolomics, and gut microbiota composition after 3 months. Discussion Controlling hyperlipidemia and inflammation is critical to preventing new cardiovascular events, but novel pharmacological treatments for these conditions are expensive and associated with negative side effects. If bilberry and/or oat, in addition to standard medical therapy, can lower LDL cholesterol and inflammation more than standard therapy alone, this could be a cost-effective and safe dietary strategy for secondary prevention after AMI. Trial registration ClinicalTrials.gov NCT03620266 . Registered on August 8, 2018.

Consumption of whole grain has been associated with lower incidence of type-2 diabetes, cardiovascular disease and their risk factors including improved glycemic control. In comparison with other whole grain products, rye bread has been shown to induce lower insulin response in the postprandial phase, without affecting the glucose response. This phenomenon has been referred to as the “rye factor” and is being explored in this review where we summarize the findings from meal and extended meal studies including rye-based foods. Overall, results from intervention studies showed that rye-based foods vs. (wheat) control foods had positive effect on both insulin and glucose responses in the postprandial phase, rather than on insulin alone. Mechanistic studies have shown that the rye factor phenomenon might be due to slowing of the glucose uptake in the intestine. However, this has also been shown for wheat-based bread and is likely an effect of structural properties of the investigated foods rather than the rye per se. More carefully controlled studies where standardized structural properties of different cereals are linked to the postprandial response are needed to further elucidate the underlying mechanisms and determinants for the effect of specific cereals and product traits on postprandial glycemic control.

The effects of early supplementation with oat β-glucan during the suckling period on piglet gut microbiota composition, concentrations of short-chain fatty acids, and gut physiological markers were assessed. Fifty piglets from five litters, balanced for sex and birth weight, were divided within litters into two treatment groups: β-glucan and control. Piglets in the β-glucan group received the supplement three times/week from day 7 of age until weaning. Rectal swab samples were collected from 10 piglets per treatment group (balanced across litters) from week 1 to week 4, and plasma samples were collected at 1, 3, and 4 weeks of age. Additional samples of intestinal tissues and jugular and portal vein plasma were collected from 10 animals at weaning (one per treatment group and litter). The concentrations of short-chain fatty acids in plasma and the microbiota composition in rectal swabs were mainly influenced by piglet age, rather than the supplement. There were significant differences in microbiota composition between litters and several correlations between concentrations of short-chain fatty acids in plasma and specific microbial taxa in rectal swabs. Overall, β-glucan supplementation did not have any clear impact on the gut environment in suckling piglets, whereas a clear age-related pattern emerged.

Phytoestrogens have been suggested to have an anti-proliferative role in prostate cancer, potentially by acting through estrogen receptor beta (ERβ) and modulating several hormones. We primarily aimed to investigate the effect of a phytoestrogen intervention on hormone concentrations in blood depending on the ERβ genotype. Patients with low and intermediate-risk prostate cancer, scheduled for radical prostatectomy, were randomized to an intervention group provided with soybeans and flaxseeds (∼200 mg phytoestrogens/d) added to their diet until their surgery, or a control group that was not provided with any food items. Both groups received official dietary recommendations. Blood samples were collected at baseline and endpoint and blood concentrations of different hormones and phytoestrogens were analyzed. The phytoestrogen-rich diet did not affect serum concentrations of testosterone, insulin-like growth factor 1, or sex hormone-binding globulin (SHBG). However, we found a trend of decreased risk of increased serum concentration of estradiol in the intervention group compared to the control group but only in a specific genotype of ERβ (p = 0.058). In conclusion, a high daily intake of phytoestrogen-rich foods has no major effect on hormone concentrations but may lower the concentration of estradiol in patients with prostate cancer with a specific genetic upset of ERβ.

Synbiotic 2000, a pre + probiotic, reduced comorbid autistic traits and emotion dysregulation in attention deficit hyperactivity disorder (ADHD) patients. Immune activity and bacteria-derived short-chain fatty acids (SCFAs) are microbiota–gut–brain axis mediators. The aim was to investigate Synbiotic 2000 effects on plasma levels of immune activity markers and SCFAs in children and adults with ADHD. ADHD patients (n = 182) completed the 9-week intervention with Synbiotic 2000 or placebo and 156 provided blood samples. Healthy adult controls (n = 57) provided baseline samples. At baseline, adults with ADHD had higher pro-inflammatory sICAM-1 and sVCAM-1 and lower SCFA levels than controls. Children with ADHD had higher baseline sICAM-1, sVCAM-1, IL-12/IL-23p40, IL-2Rα, and lower formic, acetic, and propionic acid levels than adults with ADHD. sICAM-1, sVCAM-1, and propionic acid levels were more abnormal in children on medication. Synbiotic 2000, compared to placebo, reduced IL-12/IL-23p40 and sICAM-1 and increased propionic acid levels in children on medication. SCFAs correlated negatively with sICAM-1 and sVCAM-1. Preliminary human aortic smooth-muscle-cell experiments indicated that SCFAs protected against IL-1β-induced ICAM-1 expression. These findings suggest that treatment with Synbiotic 2000 reduces IL12/IL-23p40 and sICAM-1 and increases propionic acid levels in children with ADHD. Propionic acid, together with formic and acetic acid, may contribute to the lowering of the higher-than-normal sICAM-1 levels.

Anthocyanins (ACNs) are (poly)phenols associated with reduced cardiometabolic risk. Associations between dietary intake, microbial metabolism, and cardiometabolic health benefits of ACNs have not been fully characterized. Our aims were to study the association between ACN intake, considering its dietary sources, and plasma metabolites, and to relate them with cardiometabolic risk factors in an observational study. A total of 1351 samples from 624 participants (55% female, mean age: 45 ± 12 years old) enrolled in the DCH-NG MAX study were studied using a targeted metabolomic analysis. Twenty-four-hour dietary recalls were used to collect dietary data at baseline, six, and twelve months. ACN content of foods was calculated using Phenol Explorer and foods were categorized into food groups. The median intake of total ACNs was 1.6mg/day. Using mixed graphical models, ACNs from different foods showed specific associations with plasma metabolome biomarkers. Combining these results with censored regression analysis, metabolites associated with ACNs intake were: salsolinol sulfate, 4-methylcatechol sulfate, linoleoyl carnitine, 3,4-dihydroxyphenylacetic acid, and one valerolactone. Salsolinol sulfate and 4-methylcatechol sulfate, both related to the intake of ACNs mainly from berries, were inversely associated with visceral adipose tissue. In conclusion, plasma metabolome biomarkers of dietary ACNs depended on the dietary source and some of them, such as salsolinol sulfate and 4-methylcatechol sulfate may link berry intake with cardiometabolic health benefits.

Flavonoids are bioactive plant compounds that are widely present in the human diet. Estimating flavonoid intake with a high degree of certainty is challenging due to the inherent limitations of dietary questionnaires and food composition databases. This study aimed to evaluate the degree of reliability among flavonoid intakes estimated using four different approaches based on the two most comprehensive flavonoid databases, namely, United States Department of Agriculture (USDA) and Phenol Explorer (PE). In 678 individuals from the MAX study, a subcohort of the Diet, Cancer and Health-Next Generations cohort, dietary data were collected using three 24-h diet recalls over 1 year. Estimates of flavonoid intake were compared using flavonoid food content from PE as (1) aglycones (chromatography with hydrolysis), (2) aglycones transformed (converted from glycosides by chromatography without hydrolysis), (3) as they are in nature (glycosides, aglycones, and esters), and 4) using flavonoid content from USDA as aglycones (converted). Spearman's intra-class correlation (ICC) coefficient and weighted kappa (K) coefficient were calculated for the reliability analysis. When comparing PE total aglycones to USDA total aglycones, there was a moderate reliability when a continuous variable was used [ICC: 0.73, 95% confidence interval (CI): 0.70–0.76] and an excellent reliability when flavonoid intake was modeled as a categorical variable (K: 0.89, 95% CI: 0.88–0.90). The degree of reliability among all methods of estimated flavonoid intakes was very similar, especially between database pairs, for the flavanol subclass, while larger differences were observed for flavone, flavonol, and isoflavone subclasses. Our findings indicate that caution should be taken when comparing the results of the associations between flavonoid intakes and health outcomes from studies, when flavonoid intakes were estimated using different methods, particularly for some subclasses.

Background and Aim: Plant-based diets are associated with potential health benefits, but the contribution of gut microbiota remains to be clarified. We aimed to identify differences in key features of microbiome composition and function with relevance to metabolic health in individuals adhering to a vegan vs. omnivore diet.Methods: This cross-sectional study involved lean, healthy vegans (n = 62) and omnivore (n = 33) subjects. We assessed their glucose and lipid metabolism and employed an integrated multi-omics approach (16S rRNA sequencing, metabolomics profiling) to compare dietary intake, metabolic health, gut microbiome, and fecal, serum, and urine metabolomes.Results: The vegans had more favorable glucose and lipid homeostasis profiles than the omnivores. Long-term reported adherence to a vegan diet affected only 14.8% of all detected bacterial genera in fecal microbiome. However, significant differences in vegan and omnivore metabolomes were observed. In feces, 43.3% of all identified metabolites were significantly different between the vegans and omnivores, such as amino acid fermentation products p-cresol, scatole, indole, methional (lower in the vegans), and polysaccharide fermentation product short- and medium-chain fatty acids (SCFAs, MCFAs), and their derivatives (higher in the vegans). Vegan serum metabolome differed markedly from the omnivores (55.8% of all metabolites), especially in amino acid composition, such as low BCAAs, high SCFAs (formic-, acetic-, propionic-, butyric acids), and dimethylsulfone, the latter two being potential host microbiome co-metabolites. Using a machine-learning approach, we tested the discriminative power of each dataset. Best results were obtained for serum metabolome (accuracy rate 91.6%).Conclusion: While only small differences in the gut microbiota were found between the groups, their metabolic activity differed substantially. In particular, we observed a significantly different abundance of fermentation products associated with protein and carbohydrate intakes in the vegans. Vegans had significantly lower abundances of potentially harmful (such as p-cresol, lithocholic acid, BCAAs, aromatic compounds, etc.) and higher occurrence of potentially beneficial metabolites (SCFAs and their derivatives).

Background: Patients undergoing pelvic radiotherapy are often advised to omit fiber-rich foods from their diet to reduce the adverse effects of treatment. Scientific evidence supporting this recommendation is lacking, and recent studies on animals and humans have suggested that there is a beneficial effect of dietary fiber for the alleviation of symptoms. Randomized controlled studies on dietary fiber intake during pelvic radiotherapy of sufficient size and duration are needed. As preparation for such a large-scale study, we evaluated the feasibility, compliance, participation rate, and logistics and report our findings here in this preparatory study.Methods: In this preparatory study of a fiber intervention trial, Swedish gynecological cancer patients scheduled for radiotherapy were recruited between January 2019 and August 2020. During the intervention, the participants filled out questionnaires and used an application. They also consumed a fiber supplement at first in powder form, later in capsules. Blood- and fecal samples were collected. The study is registered in clinicaltrials.gov (https://clinicaltrials.gov/ct2/show/NCT04534075?cond=fidura&draw=2&rank=1).Results: Among 136 approached patients, 57 started the study and the participation rate for primary outcomes was 63% (third blood sample) and 65% (third questionnaire). Barely half of the participants provided fecal samples. Providing concise and relevant information to the patients at the right time was crucial in getting them to participate and stay in the study. The most common reasons for declining participation or dropping out were the expected burden of radiotherapy or acute side effects. Tailoring the ambition level to each patient concerning the collection of data beyond the primary endpoints was an important strategy to keep the dropout rate at an acceptable level. Using capsules rather than psyllium in powder form made it much easier to document intake and to create a control group. During the course of the preparatory study, we improved the logistics and for the last 12 participants included, the participation rate was 100% for the earliest primary outcome.Conclusion: A variety of adjustments in this preparatory study resulted in an improved participation rate, which allowed us to set a final protocol and proceed with the main study.

Anorexia nervosa (AN) is one of the most lethal psychiatric disorders. To date, we lack adequate knowledge about the (neuro)biological mechanisms of this disorder to inform evidence-based pharmacological treatment. Gut dysbiosis is a trending topic in mental health, including AN. Communication between the gut microbiota and the brain is partly mediated by metabolites produced by the gut microbiota such as short-chain fatty acids (SCFA). Previous research has suggested a role of SCFA in weight regulation (e.g., correlations between specific SCFA-producing bacteria and BMI have been demonstrated). Moreover, fecal SCFA concentrations are reported to be altered in active AN. However, data concerning SCFA concentrations in individuals who have recovered from AN are limited. In the present study, we analyzed and compared the plasma concentrations of seven SCFA (acetic-, butyric-, formic-, isobutyric-, isovaleric-, propionic-, and succinic acid) in females with active AN (n = 109), recovered from AN (AN-REC, n = 108), and healthy-weight age-matched controls (CTRL, n = 110), and explored correlations between SCFA concentrations and BMI. Significantly lower plasma concentrations of butyric, isobutyric-, and isovaleric acid were detected in AN as well as AN-REC compared with CTRL. We also show significant correlations between plasma concentrations of SCFA and BMI. These results encourage studies evaluating whether interventions directed toward altering gut microbiota and SCFA could support weight restoration in AN.

Introduction Fatty acid (FA) concentrations have previously been associated with gestational diabetes mellitus (GDM). However, few studies on GDM have examined FA profiles in early pregnancy or before diagnosis. This study aimed to compare early pregnancy plasma FA profiles of women with and without GDM diagnoses as well as their reported dietary consumption.Research design and methods The subjects comprised 853 women from the prospective study: Pregnant Women in Iceland II (PREWICE II), attending their 11–14 weeks ultrasound appointment in 2017–2018. During the visit, blood samples were collected for plasma FA analysis, and dietary habits were assessed using a short food frequency questionnaire. Information on GDM diagnoses was then later extracted from medical records. Differences in FA profile between GDM cases and non-cases were evaluated using the Mann-Whitney U test.Results GDM was diagnosed in 127 women (14.9%). Concentrations of saturated fatty acids, monounsaturated fatty acids, polyunsaturated fatty acids (PUFA) n-6, PUFA n-3 and total FA were higher in the women who later developed GDM compared with those who did not (p≤0.05). The medians for total FA were 2898 μg/mL for the women with GDM and 2681 μg/mL for those without GDM. Mean adjusted difference for total FA between the groups was 133 μg/mL (95% CI 33 to 233). Similar results were observed in prepregnancy normal-weight women and overweight women/women with obesity. Overall diet quality in early pregnancy appeared to be lower among the women later diagnosed with GDM.Conclusion We found that plasma FA profiles in early pregnancy were different for women later diagnosed with GDM compared with those who were not, independent of the women’s body mass index.

Perfluoroalkyl substances (PFAS) are widespread persistent environmental pollutants. There is evidence that PFAS induce metabolic perturbations in humans, but underlying mechanisms are still unknown. In this exploratory study, we investigated PFAS-related plasma metabolites for their associations with type 2 diabetes (T2D) to gain potential mechanistic insight in these perturbations.We used untargeted LC-MS metabolomics to find metabolites related to PFAS exposures in a case-control study on T2D (n = 187 matched pairs) nested within the Västerbotten Intervention Programme cohort. Following principal component analysis (PCA), six PFAS measured in plasma appeared in two groups: 1) perfluorononanoic acid, perfluorodecanoic acid and perfluoroundecanoic acid and 2) perfluorohexane sulfonic acid, perfluorooctane sulfonic acid and perfluorooctanoic acid. Using a random forest algorithm, we discovered metabolite features associated with individual PFAS and PFAS exposure groups which were subsequently investigated for associations with risk of T2D.PFAS levels correlated with 171 metabolite features (0.16 ≤ |r| ≤ 0.37, false discovery rate (FDR) adjusted p

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.

Consumption of whole grain and cereal fiber have been inversely associated with body weight and obesity measures in observational studies but data from large, long-term randomized interventions are scarce. Among the cereals, rye has the highest fiber content and high rye consumption has been linked to increased production of gut fermentation products, as well as reduced risks of obesity and metabolic disease. The effects on body weight and metabolic risk factors may partly be mediated through gut microbiota and/or their fermentation products. We used data from a randomized controlled weight loss trial where participants were randomized to a hypocaloric diet rich in either high fiber rye foods or refined wheat foods for 12 weeks to investigate the effects of the intervention on gut microbiota composition and plasma short chain fatty acids, as well as the potential association with weight loss and metabolic risk markers. Rye, compared to wheat, induced some changes in gut microbiota composition, including increased abundance of the butyrate producing Agathobacter and reduced abundance of [Ruminococcus] torques group, which may be related to reductions in low grade inflammation caused by the intervention. Plasma butyrate increased in the rye group. In conclusion, intervention with high fiber rye foods induced some changes in gut microbiota composition and plasma short chain fatty acid concentration, which were associated with improvements in metabolic risk markers as a result of the intervention.

A Mediterranean-style healthy eating pattern (MED-HEP) supports metabolic health, but the utility of including low-glycemic index (GI) foods to minimize postprandial glucose excursions remain unclear. Therefore, we investigated the relative contribution of GI towards improvements in postprandial glycemia and glycemic variability after adopting a MED-HEP. We conducted a randomized, controlled dietary intervention, comparing high- versus low-GI diets in a multi-national (Italy, Sweden, and the United States) sample of adults at risk for type 2 diabetes. For 12 weeks, participants consumed either a low-GI or high-GI MED-HEP. We assessed postprandial plasma glucose and insulin responses to high- or low-GI meals, and daily glycemic variability via continuous glucose monitoring at baseline and post-intervention. One hundred sixty adults (86 females, 74 males; aged 55 ± 11 y, BMI 31 ± 3 kg/m2, mean ± SD) with ≥two metabolic syndrome traits completed the intervention. Postprandial insulin concentrations were greater after the high-GI versus the low-GI test meals at baseline (p = 0.004), but not post-intervention (p = 0.17). Postprandial glucose after the high-GI test meal increased post-intervention, being significantly higher than that after the low-GI test meal (35%, p < 0.001). Average daily glucose concentrations decreased in both groups post-intervention. Indices of 24-h glycemic variability were reduced in the low-GI group as compared to baseline and the high-GI intervention group. These findings suggest that low-GI foods may be an important feature within a MED-HEP.

Adults with central adiposity and other features of the metabolic syndrome have a markedly elevated risk of developing type 2 diabetes (T2D) and cardiovascular disease (CVD). A Mediterranean-style healthy eating pattern (MED-HEP) and consumption of foods with a lower glycemic index (GI) are potential dietary approaches to curb the T2D and CVD epidemic. However, experimental evidence of the effectiveness of MED-HEP and of the contribution of GI towards improving indices of glucose homeostasis, especially among non-diabetic people, are lacking. Therefore, we developed the MedGI-Carb trial, a multi-center (Italy, Sweden, and United States) intervention in adults with at least two components of the metabolic syndrome (elevated waist circumference + one other component) that aims to improve markers of glucose homeostasis through dietary modification. All participants were randomized to consume an isocaloric high- or low-GI MED-HEP for 12 weeks. We hypothesized that indexes of insulinemia (primary outcome: postprandial insulin and glucose after standardized breakfast and lunch; secondary outcomes: fasting plasma glucose and insulin, HbA1c, 24-h continuous glucose monitoring) would be improved more with the low-GI versus the high-GI MED-HEP. Additionally, we hypothesized that consumption of a MED-HEP would improve other markers of cardiometabolic health and well-being (fasting blood pressure, fasting lipid profile, sleep quality, satiety, global metabolic alterations in the plasma metabolome, changes in the gut microbiota, subjective health and well-being), with no difference between groups. Collectively, the design of MEDGI-Carb allows several different research questions to be explored. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03410719.

Background A vegetarian diet (VD) may reduce future cardiovascular risk in patients with ischemic heart disease. Methods and Results A randomized crossover study was conducted in subjects with ischemic heart disease, assigned to 4‐week intervention periods of isocaloric VD and meat diet (MD) with individually designed diet plans, separated by a 4‐week washout period. The primary outcome was difference in oxidized low‐density lipoprotein cholesterol (LDL‐C) between diets. Secondary outcomes were differences in cardiometabolic risk factors, quality of life, gut microbiota, fecal short‐chain and branched‐chain fatty acids, and plasma metabolome. Of 150 eligible patients, 31 (21%) agreed to participate, and 27 (87%) participants completed the study. Mean oxidized LDL‐C (−2.73 U/L), total cholesterol (−5.03 mg/dL), LDL‐C (−3.87 mg/dL), and body weight (−0.67 kg) were significantly lower with the VD than with the MD. Differences between VD and MD were observed in the relative abundance of several microbe genera within the families Ruminococcaceae, Lachnospiraceae, and Akkermansiaceae. Plasma metabolites, including l‐carnitine, acylcarnitine metabolites, and phospholipids, differed in subjects consuming VD and MD. The effect on oxidized LDL‐C in response to the VD was associated with a baseline gut microbiota composition dominated by several genera of Ruminococcaceae. Conclusions The VD in conjunction with optimal medical therapy reduced levels of oxidized LDL‐C, improved cardiometabolic risk factors, and altered the relative abundance of gut microbes and plasma metabolites in patients with ischemic heart disease. Our results suggest that composition of the gut microbiota at baseline may be related to the reduction of oxidized LDL‐C observed with the VD. Registration URL: https://www.clini​caltr​ials.gov; Unique identifier: NCT02942628.

Avenanthramides (AVAs) present in oats are amides of anthranilic and cinnamic acids. AVAs are potent antioxidants and have anti-inflammatory properties. There are various potential mechanisms for their anti-inflammatory effects, including inhibition of lipoxygenases (LOX), which catalyse oxygenation of polyunsaturated fatty acids into potent signal molecules involved in inflammatory processes. In this study, AVAs were screened for LOX inhibition in vitro and structure-activity relationships were examined. Twelve different AVAs at 0.6 mM were tested as LOX inhibitors. The corresponding free cinnamic acids, the AVA analogue Tranilast® and the known LOX inhibitor trans-resveratrol were included for comparison. It was found that AVAs comprising caffeic or sinapic acid exhibited significant lipoxygenase inhibition (60–90%) (P < 0.05), whereas low or no inhibition was observed with AVAs containing p-coumaric or ferulic acid. No difference in inhibition was seen on comparing AVAs with their free corresponding cinnamic acids, which implies that the anthranilic acid part of the avenanthramide molecule does not affect inhibition. Trans-resveratrol showed inhibition, whereas no inhibition was seen for Tranilast® at the concentrations used in this study. This study suggests that aventahtramides comprising caffeic acid or sinapic acid partly exert their antioxidant and anti-inflammatory effects via lipoxygenase inhibition.

We have developed a mobile phone application for measuring the intake of dietary fiber and validated the ability of the application to accurately capture this intake against measurements registered by a dietary record. We also investigated what food groups contributed most to the total, soluble, and insoluble dietary fiber intake. Twenty-six randomly selected Swedish women aged 35–85 years were included and randomized to either start to register dietary intake in the application or by a dietary record, during three consecutive days. After a washout period of at least two weeks, the participants used the other method. We found that the difference in measured mean fiber intake between the dietary record and the application was two grams independent of the total intake per day. A statistically significant correlation between fiber intake as measured by the two methods was found (rho = 0.65, p < 0.001). Vegetables and roots were the predominantly contributing foods to total and soluble fiber intake. Bread and crackers contributed most to insoluble fiber intake. In conclusion, the application may be considered as a useful and easy-to-use method to measure dietary fiber intake.

A vegetarian diet has been associated with a lower risk of coronary artery disease (CAD). Plasma triacylglycerols, ceramides, and phosphatidylcholines may improve prediction of recurrent coronary events. We sought to investigate effects of a lacto-ovo-vegetarian diet (VD) on plasma lipidome in CAD patients and simultaneously assess associations of plasma lipids with the extent of coronary atherosclerotic burden. We analyzed 214 plasma lipids within glycerolipid, sphingolipid, and sterol lipid classes using lipidomics from a randomized controlled, crossover trial comprising 31 CAD patients on standard medical therapy. Subjects completed a four-week intervention with VD and isocaloric meat diet (MD), separated by a four-week washout period. The VD increased levels of 11 triacylglycerols and lowered 7 triacylglycerols, 21 glycerophospholipids, cholesteryl ester (18:0), and ceramide (d18:1/16:0) compared with MD. VD increased triacylglycerols with long-chain polyunsaturated fatty acyls while decreased triacylglycerols with saturated fatty acyls, phosphatidylcholines, and sphingomyelins than MD. The Sullivan extent score (SES) exhibited on coronary angiograms were inversely associated with triacylglycerols with long-chain polyunsaturated fatty acyls. Phosphatidylcholines that were lower with VD were positively associated with SES and the total number of stenotic lesions. The VD favorably changed levels of several lipotoxic lipids that have previously been associated with increased risk of coronary events in CAD patients.

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.

Abdominal obesity is associated with elevated postprandial triglycerides (TG), an independent risk factor for cardiovascular diseases. Previous studies show that whey protein (WP) and dietary fiber may separately reduce postprandial TG. However, few studies have investigated the long-term effects of WP and dietary fiber on postprandial TG. We aimed to investigate the separate and combined long-term effects of WP and dietary fiber from wheat bran on postprandial TG and markers of lipid metabolism in subjects with abdominal obesity. We conducted a 12-week, double-blind, randomized, controlled, parallel intervention study. In a 2 × 2 factorial design, 73 adults were randomized to receive 60 g/day of either WP hydrolysate or maltodextrin (MD) combined with high-fiber wheat bran products (HiFi; 30 g dietary fiber/day) or low-fiber refined wheat products (LoFi; 10 g dietary fiber/day). A high-fat meal test was conducted before and after the intervention. Sixty-five subjects were included in the final analyses. There were no differences between intervention groups in postprandial TG assessed as incremental area under the curve (iAUC). WP-LoFi had reduced postprandial TG assessed as total area under the curve (tAUC) and reduced fasting TG compared with all other groups, and reduced fasting apolipoprotein B-48 compared with MD-LoFi. There were no changes in lipoprotein lipase activity. Total cholesterol and apolipoprotein B-100 were reduced after WP intake compared with MD. Total cholesterol was increased after HiFi intake compared with LoFi. In conclusion, intake of WP in combination with low-fiber cereal products for 12 weeks had beneficial effects on postprandial TG tAUC and fasting TG, but not on postprandial TG iAUC in subjects with abdominal obesity. Combining WP with high-fiber wheat bran products did not improve lipid profile.

Metabolomics has emerged as a promising technique to understand relationships between environmental factors and health status. Through comprehensive profiling of small molecules in biological samples, metabolomics generates high-dimensional data objectively, reflecting exposures, endogenous responses, and health effects, thereby providing further insights into exposure-disease associations. However, the multivariate nature of metabolomics data contributes to high complexity in analysis and interpretation. Efficient visualization techniques of multivariate data that allow direct interpretation of combined exposures, metabolome, and disease risk, are currently lacking. We have therefore developed the ‘triplot’ tool, a novel algorithm that simultaneously integrates and displays metabolites through latent variable modeling (e.g., principal component analysis, partial least squares regression, or factor analysis), their correlations with exposures, and their associations with disease risk estimates or intermediate risk factors. This paper illustrates the framework of the ‘triplot’ using two synthetic datasets that explore associations between dietary intake, plasma metabolome, and incident type 2 diabetes or BMI, an intermediate risk factor for lifestyle-related diseases. Our results demonstrate advantages of triplot over conventional visualization methods in facilitating interpretation in multivariate risk modeling with high-dimensional data. Algorithms, synthetic data, and tutorials are open source and available in the R package ‘triplot’.

Whole grain rye (WGR) and whole grain wheat (WGW) have been suggested to protect against the development of breast cancer. In this study, we estimated long-term intake of WGR and WGW, using both a food frequency questionnaire (FFQ) and alkylresorcinol concentrations in adipose tissue biopsies, in relation to the risk of developing invasive breast cancer in a case-cohort study (n = 414 in the case group, n = 933 in the subcohort group) on the Danish “Diet, Cancer and Health„ cohort. The median follow-up time of the subcohort was 5.3 years. Total WGR and WGW intake estimated with FFQ or reflected by total alkylresorcinol concentration in adipose tissue was not significantly associated with risk of breast cancer. However, after adjustment for total WGR and WGW intake, women in the highest quartile of relative WGR intake, reflected by the alkylresorcinol C17:0/C21:0 ratio, had a higher risk of overall breast cancer and estrogen-receptor-positive (ER+) breast cancer than women in the lowest quartile of relative WGR intake, while the risk of estrogen-receptor-negative (ER-) breast cancer incidence was unaffected. Similar results were obtained with the FFQ data. Based on these data, further investigation of the role of specific grain types in reducing or increasing breast cancer risk, and their overall impact on health, is warranted.

Background: Whole-grain foods and cereal dietary fiber intake is associated with lower body weight. This may partly result from lower energy utilization of high-fiber diets. Objective: In the present study, the impact on ileal excretion of energy and macronutrients in response to a rye bread high-fiber diet compared to a refined wheat low-fiber diet was investigated. Furthermore, the effect of meal frequency on apparent absorption of nutrients was studied for the first time. Design: Ten participants that had undergone ileostomy consumed standardized iso-caloric diets, including low-fiber wheat bread (20 g dietary fiber per day) for 2 weeks followed by high-fiber rye bread (52 g dietary fiber per day) for 2 weeks. The diets were consumed in an ordinary (three meals per day) and a nibbling (seven meals per day) meal frequency in a cross-over design. Ileal effluents were collected during 24 h at the third day of each of the four dietary periods and analyzed for gross energy and nutrient contents. Results: The results showed that intake of rye bread high-fiber diet compared to the refined wheat low-fiber diet caused an increase in ileal excretion of energy and macronutrients. The effect was independent of meal frequency. This suggests that a high intake of rye may result in lower availability of macronutrients for small intestinal digestion and absorption. A regular intake of rye may therefore have implications for weight management.

A protocol for extraction of yellow mealworm larvae proteins was established, conditions were evaluated and the resulting protein extract was characterised. The freeze-dried yellow mealworm larvae contained around 33% fat, 51% crude protein and 43% true protein on a dry matter basis. The true protein content of the protein extract was about 75%, with an extraction rate of 70% under optimised extraction conditions using 0.25 M NaOH, a NaOH solution:ethanol defatted worm ratio of 15:1 mL/g, 40°C for 1 h and extraction twice. The protein extract was a good source of essential amino acids. The lowest protein solubility in distilled water solution was found between pH 4 and 5, and increased with either increasing or decreasing pH. Lower solubility was observed in 0.5 M NaCl solution compared with distilled water. The rheological tests indicated that temperature, sample concentration, addition of salt and enzyme, incubation time and pH alterations influenced the elastic modulus of yellow mealworm protein extract (YMPE). These results demonstrate that the functional properties of YMPE can be modified for different food applications.

Sourdough fermented bread has been suggested to have beneficial health effects, in part mediated by increased satiety in the postprandial phase, but only limited research has been conducted to verify this. The current study aimed to investigate the effect of the amounts of sourdough and rye in soft bread on postprandial appetite. On 6 occasions, 23 healthy volunteers consumed 5 different test breads, with varying amount of rye and sourdough, and a yeast-fermented refined wheat control bread as part of a breakfast meal. The sourdough ranged between 9⁻51% of dough weight and rye content between 35⁻48% of flour weight. Appetite was recorded using visual analogue scales from immediately before breakfast and every 30 min the following 4 h. An ad libitum lunch was served 4 h after the breakfast meal, from which voluntary energy intake was measured. While some of the test breads resulted in lower hunger ratings and increased sense of fullness compared to the refined wheat bread, there were no differences between the test breads. The content of rye in the test breads differed within a narrow range, which might explain the lack of a consistent effect of rye on appetite. Microstructural examination of the test breads showed an increased aggregation of proteins in the breads with high content of sourdough, indicating additional changes to the breads, beyond change in pH, which may counteract the potential effect of decreased pH in the bread on appetite. In conclusion, our study does not support an effect of sourdough on appetite and ad libitum food intake.

Bioactive compounds present in plant-based foods, and their metabolites derived from gut microbiota and endogenous metabolism, represent thousands of chemical structures of potential interest for human nutrition and health. State-of-the-art analytical methodologies, including untargeted metabolomics based on high-resolution mass spectrometry, are required for the profiling of these compounds in complex matrices, including plant food materials and biofluids. The aim of this project was to compare the analytical coverage of untargeted metabolomics methods independently developed and employed in various European platforms. In total, 56 chemical standards representing the most common classes of bioactive compounds spread over a wide chemical space were selected and analyzed by the participating platforms (n = 13) using their preferred untargeted method. The results were used to define analytical criteria for a successful analysis of plant food bioactives. Furthermore, they will serve as a basis for an optimized consensus method.

Whole grain rye products have been shown to increase satiety and elicit lower postprandial insulin response without a corresponding change in glucose response compared with soft refined wheat bread. The underlying mechanisms for these effects have not been fully determined The primary aim of the study was to investigate if whole grain rye crisp bread compared to refined wheat crisp bread, elected beneficial effects on appetite and postprandial insulin response, similarly as for other rye products.In a randomized cross-over trial, 23 healthy volunteers, aged 27-70 years, BMI 18-31.4 kg/m2, were served a standardized breakfast with unfermented whole grain rye crisp bread (uRCB), fermented whole grain rye crisp bread (RCB) or refined wheat crisp bread (WCB), Appetite was measured using a visual analogue scale (VAS) until 4 h after breakfast. Postprandial glucose and insulin were measured at 0-230 min. Breads were chemically characterized including macronutrients, energy, dietary fiber components, and amino acid composition, and microstructure was characterized with light microscopy.Reported fullness was 16% higher (P

Few studies have explored the possible plasma cholesterol lowering effects of rye consumption. The aim of this secondary analysis in the SYSDIET study was to investigate the association between plasma alkylresorcinols (AR), a biomarker for whole grain wheat and rye intake, and blood lipid concentrations in a population with metabolic syndrome. Furthermore, we analyzed the associations between the AR C17:0/C21:0 ratio, a suggested marker of the relative intake of whole grain/bran rye, and blood lipid concentrations.Participants were 30-65 years of age, with body mass index (BMI) 27-40 kg/m2 and had metabolic syndrome. Individuals were recruited through six centers in the Nordic countries and randomized either to a healthy Nordic diet (ND, n = 93), rich in whole grain rye and wheat, as well as berries, fruits and vegetables, rapeseed oil, three fish meals per week and low-fat dairy products, or a control diet (n = 65) for 18/24 weeks. Associations between total plasma AR concentration and C17:0/C21:0 homologue ratio and blood lipids were investigated in pooled (ND + control group) regression analyses at 18/24 weeks adjusted for baseline value for the dependent variable, age, BMI and statin use.When adjusted for confounders, total plasma AR at 18/24 weeks was not significantly associated with blood lipids but the AR ratio C17:0/C21:0 was inversely associated with LDL cholesterol concentrations (B (95% CI): -0.41 (-0.80 to -0.02)), log LDL/HDL cholesterol ratio (-0.20 (-0.37 to -0.03)), log non-HDL cholesterol (-0.20 (-0.37 to -0.03)), log apolipoprotein B (-0.12 (-0.24 to 0.00)) and log triglyceride concentrations (-0.35 (-0.59 to -0.12)).Increased proportion of whole grain rye, reflected by a biomarker, in the diet is associated with favorable blood lipid outcomes, a relationship that should be further investigated.ClinicalTrials.gov NCT00992641.