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The intestinal microbiome is a co-determinant of the postprandial plasma glucose response.
Søndertoft, NB, Vogt, JK, Arumugam, M, Kristensen, M, Gøbel, RJ, Fan, Y, Lyu, L, Bahl, MI, Eriksen, C, Ängquist, L, et al
PloS one. 2020;(9):e0238648
Abstract
Elevated postprandial plasma glucose is a risk factor for development of type 2 diabetes and cardiovascular disease. We hypothesized that the inter-individual postprandial plasma glucose response varies partly depending on the intestinal microbiome composition and function. We analyzed data from Danish adults (n = 106), who were self-reported healthy and attended the baseline visit of two previously reported randomized controlled cross-over trials within the Gut, Grain and Greens project. Plasma glucose concentrations at five time points were measured before and during three hours after a standardized breakfast. Based on these data, we devised machine learning algorithms integrating bio-clinical, as well as shotgun-sequencing-derived taxa and functional potentials of the intestinal microbiome to predict individual postprandial glucose excursions. In this post hoc study, we found microbial and clinical features, which predicted up to 48% of the inter-individual variance of postprandial plasma glucose responses (Pearson correlation coefficient of measured vs. predicted values, R = 0.69, 95% CI: 0.45 to 0.84, p<0.001). The features were age, fasting serum triglycerides, systolic blood pressure, BMI, fasting total serum cholesterol, abundance of Bifidobacterium genus, richness of metagenomics species and abundance of a metagenomic species annotated to Clostridiales at order level. A model based only on microbial features predicted up to 14% of the variance in postprandial plasma glucose excursions (R = 0.37, 95% CI: 0.02 to 0.64, p = 0.04). Adding fasting glycaemic measures to the model including microbial and bio-clinical features increased the predictive power to R = 0.78 (95% CI: 0.59 to 0.89, p<0.001), explaining more than 60% of the inter-individual variance of postprandial plasma glucose concentrations. The outcome of the study points to a potential role of the taxa and functional potentials of the intestinal microbiome. If validated in larger studies our findings may be included in future algorithms attempting to develop personalized nutrition, especially for prediction of individual blood glucose excursions in dys-glycaemic individuals.
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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.
Roager, HM, Vogt, JK, Kristensen, M, Hansen, LBS, Ibrügger, S, Mærkedahl, RB, Bahl, MI, Lind, MV, Nielsen, RL, Frøkiær, H, et al
Gut. 2019;68(1):83-93
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Plain language summary
Whole grain consumption has been linked with decreased risk of lifestyle-related diseases. While animal studies have shown the gut microbiome to be a mediator of metabolic health, human studies examining the effect of whole grain intake of the gut remain inconclusive. The aim of this study was to investigate the effects of a whole grain diet on the gut microbiome, gut functionality and biomarkers of metabolic health. In this randomised, controlled, crossover study, 50 participants completed two 8-week dietary intervention periods comprising of a whole grain diet and a refined grain diet with a 6-week washout period. Examinations were done at the beginning and end of each intervention period to assess anthropometry and various plasma and gut markers. This study found that a whole grain diet as compared with a refined grain diet reduced energy intake and body weight as well as circulating markers of inflammation. Contrary to the hypothesis, these benefits were all observed independent of changes in the gut microbiome. Based on these results, the authors conclude higher intake of whole grains should be recommended to those at risk of inflammation-related disease.
Abstract
OBJECTIVE To investigate whether a whole grain diet alters the gut microbiome and insulin sensitivity, as well as biomarkers of metabolic health and gut functionality. DESIGN 60 Danish adults at risk of developing metabolic syndrome were included in a randomised cross-over trial with two 8-week dietary intervention periods comprising whole grain diet and refined grain diet, separated by a washout period of ≥6 weeks. The response to the interventions on the gut microbiome composition and insulin sensitivity as well on measures of glucose and lipid metabolism, gut functionality, inflammatory markers, anthropometry and urine metabolomics were assessed. RESULTS 50 participants completed both periods with a whole grain intake of 179±50 g/day and 13±10 g/day in the whole grain and refined grain period, respectively. Compliance was confirmed by a difference in plasma alkylresorcinols (p<0.0001). Compared with refined grain, whole grain did not significantly alter glucose homeostasis and did not induce major changes in the faecal microbiome. Also, breath hydrogen levels, plasma short-chain fatty acids, intestinal integrity and intestinal transit time were not affected. The whole grain diet did, however, compared with the refined grain diet, decrease body weight (p<0.0001), serum inflammatory markers, interleukin (IL)-6 (p=0.009) and C-reactive protein (p=0.003). The reduction in body weight was consistent with a reduction in energy intake, and IL-6 reduction was associated with the amount of whole grain consumed, in particular with intake of rye. CONCLUSION Compared with refined grain diet, whole grain diet did not alter insulin sensitivity and gut microbiome but reduced body weight and systemic low-grade inflammation. TRIAL REGISTRATION NUMBER NCT01731366; Results.
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A low-gluten diet induces changes in the intestinal microbiome of healthy Danish adults.
Hansen, LBS, Roager, HM, Søndertoft, NB, Gøbel, RJ, Kristensen, M, Vallès-Colomer, M, Vieira-Silva, S, Ibrügger, S, Lind, MV, Mærkedahl, RB, et al
Nature communications. 2018;(1):4630
Abstract
Adherence to a low-gluten diet has become increasingly common in parts of the general population. However, the effects of reducing gluten-rich food items including wheat, barley and rye cereals in healthy adults are unclear. Here, we undertook a randomised, controlled, cross-over trial involving 60 middle-aged Danish adults without known disorders with two 8-week interventions comparing a low-gluten diet (2 g gluten per day) and a high-gluten diet (18 g gluten per day), separated by a washout period of at least six weeks with habitual diet (12 g gluten per day). We find that, in comparison with a high-gluten diet, a low-gluten diet induces moderate changes in the intestinal microbiome, reduces fasting and postprandial hydrogen exhalation, and leads to improvements in self-reported bloating. These observations suggest that most of the effects of a low-gluten diet in non-coeliac adults may be driven by qualitative changes in dietary fibres.
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Plasma Alkylresorcinols Reflect Gluten Intake and Distinguish between Gluten-Rich and Gluten-Poor Diets in a Population at Risk of Metabolic Syndrome.
Lind, MV, Madsen, ML, Rumessen, JJ, Vestergaard, H, Gøbel, RJ, Hansen, T, Lauritzen, L, Pedersen, OB, Kristensen, M, Ross, AB
The Journal of nutrition. 2016;(10):1991-1998
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Abstract
BACKGROUND Many patients with celiac disease experience difficulties in adherence to a gluten-free diet. Methods for testing compliance to a gluten-free diet are costly and cumbersome. Thus, a simple biomarker of gluten intake is needed in a clinical setting and will be useful for epidemiologic studies investigating wider effects of gluten intake. OBJECTIVE The aim was to evaluate plasma total alkylresorcinol concentrations as a measure of gluten intake. METHODS In this randomized, controlled, crossover intervention study in 52 Danish adults with features of the metabolic syndrome, we compared 8 wk of a gluten-rich and gluten-poor diet separated by a washout period of ≥6 wk. We measured fasting plasma concentrations of alkylresorcinols to determine if they reflected differences in gluten intake as a secondary outcome of the original study. In addition, we investigated in 118 Danish adults the cross-sectional association between self-reported gluten intake and plasma alkylresorcinols in the same and a similar study at baseline. We used mixed-model ANCOVA for examining treatment effects, a classification tree to determine compliance to the gluten-poor diet, and linear regression models for examining baseline correlation between plasma alkylresorcinol concentrations and gluten intake. RESULTS Plasma total alkylresorcinols decreased more during the gluten-poor period (geometric mean: -124.8 nmol/L; 95% CI: -156.5, -93.0 nmol/L) than in the gluten-rich period (geometric mean: -31.8 nmol/L; 95% CI: -63.1, -0.4 nmol/L) (P < 0.001). On the basis of the plasma alkylresorcinol profile, we built a classification tree to objectively determine compliance and found an overall participant misclassification error of 3.9%. In the cross-sectional study we found a 5.6% (95% CI: 2.4%, 8.9%) increase in plasma total alkylresorcinols per 1-g increase in reported gluten intake (P < 0.001). CONCLUSION We propose the use of plasma alkylresorcinols to monitor compliance to a gluten-free diet as well as to help investigations into the possible effects of gluten in the wider population. This trial was registered at www.clinicaltrials.gov as NCT017119913 and NCT01731366.
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Effect of Lactobacillus salivarius Ls-33 on fecal microbiota in obese adolescents.
Larsen, N, Vogensen, FK, Gøbel, RJ, Michaelsen, KF, Forssten, SD, Lahtinen, SJ, Jakobsen, M
Clinical nutrition (Edinburgh, Scotland). 2013;(6):935-40
Abstract
BACKGROUND & AIMS This study is a part of the clinical trials with probiotic bacterium Lactobacillus salivarius Ls-33 conducted in obese adolescents. Previously reported clinical studies showed no effect of Ls-33 consumption on the metabolic syndrome in the subject group. The aim of the study was to investigate the impact of L. salivarius Ls-33 on fecal microbiota in obese adolescents. METHODS The study was a double-blinded intervention with 50 subjects randomized to intake of L. salivarius Ls-33 or placebo for 12 weeks. The fecal microbiota was assessed by real-time quantitative PCR before and after intervention. Concentrations of fecal short chain fatty acids were determined using gas chromatography. RESULTS Ratios of Bacteroides-Prevotella-Porphyromonas group to Firmicutes belonging bacteria, including Clostridium cluster XIV, Blautia coccoides_Eubacteria rectale group and Roseburia intestinalis, were significantly increased (p ≤ 0.05) after administration of Ls-33. The cell numbers of fecal bacteria, including the groups above as well as Clostridium cluster I, Clostridium cluster IV, Faecalibacterium prausnitzii, Enterobacteriaceae, Enterococcus, the Lactobacillus group and Bifidobacterium were not significantly altered by intervention. Similarly, short chain fatty acids remained unaffected. CONCLUSION L. salivarius Ls-33 might modify the fecal microbiota in obese adolescents in a way not related to metabolic syndrome. CLINICAL TRIAL NUMBER NCT 01020617.
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Probiotics to adolescents with obesity: effects on inflammation and metabolic syndrome.
Gøbel, RJ, Larsen, N, Jakobsen, M, Mølgaard, C, Michaelsen, KF
Journal of pediatric gastroenterology and nutrition. 2012;(6):673-8
Abstract
OBJECTIVES The connections between gut microbiota, energy homeostasis, and inflammation and its role in the pathogenesis of obesity-related disorders are increasingly recognized. We aimed to investigate the effect of the probiotic strain Lactobacillus salivarius Ls-33 on a series of biomarkers related to inflammation and the metabolic syndrome (MS) in adolescents with obesity. METHODS The study was a double-blind placebo-controlled trial including 50 adolescents with obesity randomized to Ls-33 (10 CFU) or placebo daily for 12 weeks. RESULTS The average body mass index-for-age z-score was 2.6 ± 0.5. There were no differences in biomarkers of inflammation and parameters related to the MS at baseline between the probiotic and placebo groups. Furthermore, there were no differences in changes from baseline to 12-week intervention with regard to any anthropometric measures, blood pressure (systolic and diastolic), fasting glucose and insulin, homeostasis model assessment of insulin resistance, C-peptide, cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglyceride, free fatty acids, C-reactive protein, interleukin-6, tumor necrosis factor alpha, or fecal calprotectin, despite the increased values of biomarkers of inflammation and of several parameters related to the MS at baseline when compared with normal-weight adolescents. The levels of L salivarius in fecal samples from the probiotic group in the present study were comparable with the levels reported for the other probiotic lactobacilli and bifidobacteria using quantitative polymerase chain reaction. CONCLUSIONS It was not possible to detect any beneficial effect of the probiotic intervention with Ls-33 on inflammatory markers or parameters related to the MS in adolescents with obesity being in a state of low-grade systemic inflammation.