Effects of whole-grain wheat, rye, and lignan supplementation on cardiometabolic risk factors in men with metabolic syndrome: a randomized crossover trial.

BACKGROUND A whole-grain (WG)-rich diet has shown to have potential for both prevention and treatment of the metabolic syndrome (MetS), which is a cluster of risk factors that increase the risk of type 2 diabetes and cardiovascular disease. Different WGs may have different health effects. WG rye, in particular, may improve glucose homeostasis and blood lipids, possibly mediated through fermentable dietary fiber and lignans. Recent studies have also suggested a crucial role of the gut microbiota in response to WG. OBJECTIVES The aim was to investigate WG rye, alone and with lignan supplements [secoisolariciresinol diglucoside (SDG)], and WG wheat diets on glucose tolerance [oral-glucose-tolerance test (OGTT)], other cardiometabolic outcomes, enterolignans, and microbiota composition. Moreover, we exploratively evaluated the role of gut microbiota enterotypes in response to intervention diets. METHODS Forty men with MetS risk profile were randomly assigned to WG diets in an 8-wk crossover study. The rye diet was supplemented with 280 mg SDG at weeks 4-8. Effects of treatment were evaluated by mixed-effects modeling, and effects on microbiota composition and the role of gut microbiota as a predictor of response to treatment were analyzed by random forest plots. RESULTS The WG rye diet (± SDG supplements) did not affect the OGTT compared with WG wheat. Total and LDL cholesterol were lowered (-0.06 and -0.09 mmol/L, respectively; P < 0.05) after WG rye compared with WG wheat after 4 wk but not after 8 wk. WG rye resulted in higher abundance of Bifidobacterium [fold-change (FC) = 2.58, P < 0.001] compared with baseline and lower abundance of Clostridium genus compared with WG wheat (FC = 0.54, P = 0.02). The explorative analyses suggest that baseline enterotype is associated with total and LDL-cholesterol response to diet. CONCLUSIONS WG rye, alone or with SDG supplementation, compared with WG wheat did not affect glucose metabolism but caused transient LDL-cholesterol reduction. The effect of WG diets appeared to differ according to enterotype. This trial was registered at www.clinicaltrials.gov as NCT02987595.

[1]  A. Astrup,et al.  Prevotella Abundance Predicts Weight Loss Success in Healthy, Overweight Adults Consuming a Whole-Grain Diet Ad Libitum: A Post Hoc Analysis of a 6-Wk Randomized Controlled Trial. , 2019, The Journal of nutrition.

[2]  L. T. Te Morenga,et al.  Carbohydrate quality and human health: a series of systematic reviews and meta-analyses , 2019, The Lancet.

[3]  Lin Shi,et al.  Variable selection and validation in multivariate modelling , 2018, Bioinform..

[4]  S. Rampelli,et al.  Arabinoxylan oligosaccharides and polyunsaturated fatty acid effects on gut microbiota and metabolic markers in overweight individuals with signs of metabolic syndrome: A randomized cross-over trial. , 2019, Clinical nutrition.

[5]  A. Tjønneland,et al.  Rye and health - Where do we stand and where do we go? , 2018, Trends in Food Science & Technology.

[6]  K. Kristiansen,et al.  Prevotella-to-Bacteroides ratio predicts body weight and fat loss success on 24-week diets varying in macronutrient composition and dietary fiber: results from a post-hoc analysis , 2018, International Journal of Obesity.

[7]  Chenhong Zhang,et al.  Gut bacteria selectively promoted by dietary fibers alleviate type 2 diabetes , 2018, Science.

[8]  T. R. Licht,et al.  Pre-treatment microbial Prevotella-to-Bacteroides ratio, determines body fat loss success during a 6-month randomized controlled diet intervention , 2017, International Journal of Obesity.

[9]  R. L. Nielsen,et al.  Whole grain-rich diet reduces body weight and systemic low-grade inflammation without inducing major changes of the gut microbiome: a randomised cross-over trial , 2017, Gut.

[10]  Jun Wang,et al.  Quantitative microbiome profiling links gut community variation to microbial load , 2017, Nature.

[11]  C. Marsaux,et al.  A review of the characteristics of dietary fibers relevant to appetite and energy intake outcomes in human intervention trials. , 2017, The American journal of clinical nutrition.

[12]  S. Delgado,et al.  Bifidobacteria and Their Health-Promoting Effects. , 2017, Microbiology spectrum.

[13]  Eran Segal,et al.  Bread Affects Clinical Parameters and Induces Gut Microbiome-Associated Personal Glycemic Responses. , 2017, Cell metabolism.

[14]  B. Hamaker,et al.  Fiber-utilizing capacity varies in Prevotella- versus Bacteroides-dominated gut microbiota , 2017, Scientific Reports.

[15]  Jussi Paananen,et al.  Indolepropionic acid and novel lipid metabolites are associated with a lower risk of type 2 diabetes in the Finnish Diabetes Prevention Study , 2017, Scientific Reports.

[16]  R. Landberg,et al.  Wholegrain rye, but not wholegrain wheat, lowers body weight and fat mass compared with refined wheat: a 6-week randomized study , 2017, European Journal of Clinical Nutrition.

[17]  A. Engin,et al.  The Definition and Prevalence of Obesity and Metabolic Syndrome. , 2017, Advances in experimental medicine and biology.

[18]  Falk Hildebrand,et al.  Enterotypes in the landscape of gut microbial community composition , 2017, Nature Microbiology.

[19]  N. Nørskov,et al.  Validated LC-MS/MS Method for the Quantification of Free and Bound Lignans in Cereal-Based Diets and Feces. , 2016, Journal of agricultural and food chemistry.

[20]  F. Bäckhed,et al.  Diet–microbiota interactions as moderators of human metabolism , 2016, Nature.

[21]  N. Pariente,et al.  Intestinal microbiota in health and disease , 2016, Nature.

[22]  Frédéric Leroy,et al.  Bifidobacteria and Butyrate-Producing Colon Bacteria: Importance and Strategies for Their Stimulation in the Human Gut , 2016, Front. Microbiol..

[23]  J. Kirwan,et al.  A high-throughput method for liquid chromatography-tandem mass spectrometry determination of plasma alkylresorcinols, biomarkers of whole grain wheat and rye intake. , 2016, Analytical biochemistry.

[24]  Jian-Min Yuan,et al.  Urine phyto-oestrogen metabolites are not significantly associated with risk of type 2 diabetes: the Singapore Chinese health study , 2016, British Journal of Nutrition.

[25]  A. Schnürer,et al.  Bacterial community composition and fhs profiles of low- and high-ammonia biogas digesters reveal novel syntrophic acetate-oxidising bacteria , 2016, Biotechnology for Biofuels.

[26]  D. Mozaffarian.  Dietary and Policy Priorities for Cardiovascular Disease, Diabetes, and Obesity: A Comprehensive Review , 2016, Circulation.

[27]  F. Bäckhed,et al.  Dietary Fiber-Induced Improvement in Glucose Metabolism Is Associated with Increased Abundance of Prevotella. , 2015, Cell metabolism.

[28]  A. Tjønneland,et al.  Targeted LC-MS/MS Method for the Quantitation of Plant Lignans and Enterolignans in Biofluids from Humans and Pigs. , 2015, Journal of agricultural and food chemistry.

[29]  J. Pihlajamäki,et al.  Postprandial glucose metabolism and SCFA after consuming wholegrain rye bread and wheat bread enriched with bioprocessed rye bran in individuals with mild gastrointestinal symptoms , 2014, Nutrition Journal.

[30]  A. Whitehead,et al.  Cholesterol-lowering effects of oat β-glucan: a meta-analysis of randomized controlled trials1234 , 2014, The American journal of clinical nutrition.

[31]  L. Lauritzen,et al.  Second meal effect on appetite and fermentation of wholegrain rye foods , 2014, Appetite.

[32]  E. Rimm,et al.  Gut Microbiota Metabolites of Dietary Lignans and Risk of Type 2 Diabetes: A Prospective Investigation in Two Cohorts of U.S. Women , 2014, Diabetes Care.

[33]  M. Breton,et al.  Effects of exercise intensity on postprandial improvement in glucose disposal and insulin sensitivity in prediabetic adults. , 2014, The Journal of clinical endocrinology and metabolism.

[34]  T. R. Licht,et al.  Microbial Enterotypes, Inferred by the Prevotella-to-Bacteroides Ratio, Remained Stable during a 6-Month Randomized Controlled Diet Intervention with the New Nordic Diet , 2013, Applied and Environmental Microbiology.

[35]  D. van der A,et al.  The Association Between Dietary Flavonoid and Lignan Intakes and Incident Type 2 Diabetes in European Populations , 2013, Diabetes Care.

[36]  J. Hallund,et al.  Dietary intake and main sources of plant lignans in five European countries , 2013, Food & nutrition research.

[37]  H. Kwon,et al.  Metabolic syndrome as a predictor of type 2 diabetes, and its clinical interpretations and usefulness , 2013, Journal of diabetes investigation.

[38]  W. D. de Vos,et al.  Intake of whole-grain and fiber-rich rye bread versus refined wheat bread does not differentiate intestinal microbiota composition in Finnish adults with metabolic syndrome. , 2013, The Journal of nutrition.

[39]  L. Lind,et al.  EpiHealth: a large population-based cohort study for investigation of gene–lifestyle interactions in the pathogenesis of common diseases , 2013, European Journal of Epidemiology.

[40]  P. Shewry,et al.  Contents of dietary fibre components and their relation to associated bioactive components in whole grain wheat samples from the HEALTHGRAIN diversity screen. , 2013, Food chemistry.

[41]  A. Wolk,et al.  Validation of FFQ-based assessment of dietary lignans compared with serum enterolactone in Swedish women , 2012, British Journal of Nutrition.

[42]  A. Ross.  Present Status and Perspectives on the Use of Alkylresorcinols as Biomarkers of Wholegrain Wheat and Rye Intake , 2012, Journal of nutrition and metabolism.

[43]  P. Bork,et al.  Enterotypes of the human gut microbiome , 2011, Nature.

[44]  Anders F. Andersson,et al.  Transitions in bacterial communities along the 2000 km salinity gradient of the Baltic Sea , 2011, The ISME Journal.

[45]  A. Fardet.  New hypotheses for the health-protective mechanisms of whole-grain cereals: what is beyond fibre? , 2010, Nutrition Research Reviews.

[46]  William A. Walters,et al.  QIIME allows analysis of high-throughput community sequencing data , 2010, Nature Methods.

[47]  P. Åman,et al.  Whole grain for whom and why? , 2010, Food & nutrition research.

[48]  Age K. Smilde,et al.  Multivariate paired data analysis: multilevel PLSDA versus OPLSDA , 2009, Metabolomics.

[49]  S. Grundy,et al.  Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International As , 2009, Circulation.

[50]  P. Åman,et al.  Content and molecular-weight distribution of dietary fiber components in whole-grain rye flour and bread. , 2009, Journal of agricultural and food chemistry.

[51]  Wei Zhang,et al.  Dietary flaxseed lignan extract lowers plasma cholesterol and glucose concentrations in hypercholesterolaemic subjects , 2008, British Journal of Nutrition.

[52]  James W. Anderson,et al.  Grain Foods and Health: A Primer for Clinicians , 2008, The Physician and sportsmedicine.

[53]  W. Demark-Wahnefried,et al.  Effects of a Flaxseed-Derived Lignan Supplement in Type 2 Diabetic Patients: A Randomized, Double-Blind, Cross-Over Trial , 2007, PloS one.

[54]  L. Niskanen,et al.  Interaction between cholesterol and glucose metabolism during dietary carbohydrate modification in subjects with the metabolic syndrome. , 2006, The American journal of clinical nutrition.

[55]  E. Rimm,et al.  The usual intake of lignans but not that of isoflavones may be related to cardiovascular risk factors in U.S. men. , 2005, The Journal of nutrition.

[56]  E. Mayer-Davis,et al.  Whole-grain intake and insulin sensitivity: the Insulin Resistance Atherosclerosis Study. , 2003, The American journal of clinical nutrition.

[57]  M. Noakes,et al.  Whole-grain rye and wheat foods and markers of bowel health in overweight middle-aged men. , 2003, The American journal of clinical nutrition.

[58]  K. Poutanen,et al.  Rye bread decreases serum total and LDL cholesterol in men with moderately elevated serum cholesterol. , 2000, The Journal of nutrition.

[59]  I. Björck,et al.  Influence of orally and rectally administered propionate on cholesterol and glucose metabolism in obese rats , 1996, British Journal of Nutrition.

[60]  R. Andersson,et al.  Total dietary fiber determined as neutral sugar residues, uronic acid residues, and Klason lignin (the Uppsala method): collaborative study. , 1995, Journal of AOAC International.

[61]  G R Gibson,et al.  Dietary modulation of the human colonic microbiota: introducing the concept of prebiotics. , 1995, The Journal of nutrition.