Effect of atorvastatin on C-reactive protein and benefits for cardiovascular disease in patients with type 2 diabetes: analyses from the Collaborative Atorvastatin Diabetes Trial
Soedamah-Muthu, S.S. ; Livingstone, S.J. ; Charlton-Menys, V. ; Betteridge, D.J. ; Hitman, G.A. ; Neil, H.A.W. ; Bao, W. ; DeMicco, D.A. ; Preston, G.M. ; Fuller, J.H. ; Stehouwer, C.D.A. ; Schalkwijk, C.G. ; Durrington, P.N. ; Colhoun, H.M. - \ 2015
Diabetologia 58 (2015)7. - ISSN 0012-186X - p. 1494 - 1502.
placebo-controlled trial - acute coronary syndromes - cardiac outcomes trial - statin therapy - myocardial-infarction - on-treatment - follow-up - cholesterol - mortality - heart
Aims/hypothesis We investigated whether atorvastatin 10 mg daily lowered C-reactive protein (CRP) and whether the effects of atorvastatin on cardiovascular disease (CVD) varied by achieved levels of CRP and LDL-cholesterol. Methods CRP levels were measured at baseline and 1 year after randomisation to atorvastatin in 2,322 patients with type 2 diabetes (40–75 years, 69% males) in a secondary analysis of the Collaborative Atorvastatin Diabetes Study, a randomised placebo-controlled trial. We used Cox regression models to test the effects on subsequent CVD events (n¿=¿147) of CRP and LDL-cholesterol lowering at 1 year. Results After 1 year, the atorvastatin arm showed a net CRP lowering of 32% (95% CI -40%, -22%) compared with placebo. The CRP response was highly variable, with 45% of those on atorvastatin having no decrease in CRP (median [interquartile range, IQR] per cent change -9.8% [-57%, 115%]). The LDL-cholesterol response was less variable, with a median (IQR) within-person per cent change of -41% (-51%, -31%). Baseline CRP did not predict CVD over 3.8 years of follow-up (HRper SD log 0.89 [95% CI 0.75, 1.06]), whereas baseline LDL-cholesterol predicted CVD (HRper SD 1.21 [95% CI 1.02, 1.44]), as did on-treatment LDL-cholesterol. There was no significant difference in the reduction in CVD by atorvastatin, with above median (HR 0.57) or below median (HR 0.52) change in CRP or change in LDL-cholesterol (HR 0.61 vs 0.50). Conclusions/interpretation CRP was not a strong predictor of CVD. Statin efficacy did not vary with achieved CRP despite considerable variability in CRP response. The use of CRP as an indicator of efficacy of statin therapy on CVD risk in patients with type 2 diabetes is not supported by these data.
Effect of vitamin B12 and folic acid supplementation on bone mineral density and quantitative ultrasound parameters in older people with an elevated plasma homocysteine level: B-PROOF, a randomized controlled trial
Enneman, A.W. ; Swart, K.M.A. ; Wijngaarden, J.P. van; Dijk, S.C. van; Ham, A.C. ; Brouwer-Brolsma, E.M. ; Zwaluw, N.L. van der; Dhonukshe-Rutten, R.A.M. ; Cammen, T.J.M. van der; Groot, C.P.G.M. de; Meurs, J.B.J. van; Lips, P. ; Uitterlinden, A.G. ; Zillikens, M.C. ; Schoor, N.M. van; Velde, N. van der - \ 2015
Calcified Tissue International 96 (2015)5. - ISSN 0171-967X - p. 401 - 409.
placebo-controlled trial - postmenopausal women - fracture risk - turnover markers - elderly-women - metaanalysis - association - population - folate - bmd
High plasma homocysteine (Hcy) levels are associated with increased osteoporotic fracture incidence. However, the mechanism remains unclear. We investigated the effect of Hcy-lowering vitamin B12 and folic acid treatment on bone mineral density (BMD) and calcaneal quantitative ultrasound (QUS) parameters. This randomized, double-blind, placebo-controlled trial included participants aged =65 years with plasma Hcy levels between 12 and 50 µmol/L. The intervention comprised 2-year supplementation with either a combination of 500 µg B12, 400 µg folic acid, and 600 IU vitamin D or placebo with 600 IU vitamin D only. In total, 1111 participants underwent repeated dual-energy X-ray assessment and 1165 participants underwent QUS. Femoral neck (FN) BMD, lumbar spine (LS) BMD, calcaneal broadband ultrasound attenuation (BUA), and calcaneal speed of sound (SOS) were assessed. After 2 years, FN-BMD and BUA had significantly decreased, while LS-BMD significantly increased (all p <0.01) and SOS did not change in either treatment arm. No statistically significant differences between the intervention and placebo group were present for FN-BMD (p = 0.24), LS-BMD (p = 0.16), SOS (p = 0.67), and BUA (p = 0.96). However, exploratory subgroup analyses revealed a small positive effect of the intervention on BUA at follow-up among compliant persons >80 years (estimated marginal mean 64.4 dB/MHz for the intervention group and 61.0 dB/MHz for the placebo group, p = 0.04 for difference). In conclusion, this study showed no overall effect of treatment with vitamin B12 and folic acid on BMD or QUS parameters in elderly, mildly hyperhomocysteinemic persons, but suggests a small beneficial effect on BUA in persons >80 years who were compliant in taking the supplement.
Handgrip strength does not represent an appropriate measure to evaluate changes in muscle strength during an exercise intervention program in frail elderly people
Tieland, C.A.B. ; Verdijk, L. ; Groot, C.P.G.M. de; Loon, L.J.C. van - \ 2015
International Journal of Sport Nutrition & Exercise Metabolism 25 (2015). - ISSN 1526-484X - p. 27 - 36.
randomized controlled-trial - placebo-controlled trial - healthy elderly-women - bone-mineral density - protein supplementation - physical performance - training-program - body-composition - resistance exercise - muscular strength
Although handgrip strength is considered a strong predictor of negative health outcomes, it is unclear whether handgrip strength represents a useful measure to evaluate changes in muscle strength following resistance-type exercise training in elderly people. We assessed whether measuring handgrip strength provides proper insight in the efficacy of resistance-type exercise training to increase muscle mass, strength and physical performance in frail elderly. Methods: Pre-frail and frail elderly (=65 y) were either conducting a 24 wk resistance-type exercise training or no exercise training. Before, during, and after the intervention, handgrip strength (JAMAR), lean body mass (DXA), leg strength (1-RM), and physical performance (SPPB) were assessed. Results: Handgrip strength correlated with appendicular lean mass (¿ =0.68; P
Intestinal permeability - a new target for disease prevention and therapy
Bischoff, S.C. ; Barbara, G. ; Buurman, W. ; Ockhuizen, T. ; Schulzke, J.D. ; Serino, M. ; Tilg, H. ; Watson, A. ; Wells, J.M. - \ 2014
BMC Gastroenterology 14 (2014). - ISSN 1471-230X - 25 p.
irritable-bowel-syndrome - placebo-controlled trial - enteropathogenic escherichia-coli - severe acute-pancreatitis - helicobacter-pylori caga - high-fat diet - clostridium-difficile infection - serotonin reuptake transporter - epithelial barrier function - apical
Data are accumulating that emphasize the important role of the intestinal barrier and intestinal permeability for health and disease. However, these terms are poorly defined, their assessment is a matter of debate, and their clinical significance is not clearly established. In the present review, current knowledge on mucosal barrier and its role in disease prevention and therapy is summarized. First, the relevant terms ‘intestinal barrier’ and ‘intestinal permeability’ are defined. Secondly, the key element of the intestinal barrier affecting permeability are described. This barrier represents a huge mucosal surface, where billions of bacteria face the largest immune system of our body. On the one hand, an intact intestinal barrier protects the human organism against invasion of microorganisms and toxins, on the other hand, this barrier must be open to absorb essential fluids and nutrients. Such opposing goals are achieved by a complex anatomical and functional structure the intestinal barrier consists of, the functional status of which is described by ‘intestinal permeability’. Third, the regulation of intestinal permeability by diet and bacteria is depicted. In particular, potential barrier disruptors such as hypoperfusion of the gut, infections and toxins, but also selected over-dosed nutrients, drugs, and other lifestyle factors have to be considered. In the fourth part, the means to assess intestinal permeability are presented and critically discussed. The means vary enormously and probably assess different functional components of the barrier. The barrier assessments are further hindered by the natural variability of this functional entity depending on species and genes as well as on diet and other environmental factors. In the final part, we discuss selected diseases associated with increased intestinal permeability such as critically illness, inflammatory bowel diseases, celiac disease, food allergy, irritable bowel syndrome, and – more recently recognized – obesity and metabolic diseases. All these diseases are characterized by inflammation that might be triggered by the translocation of luminal components into the host. In summary, intestinal permeability, which is a feature of intestinal barrier function, is increasingly recognized as being of relevance for health and disease, and therefore, this topic warrants more attention.
Results of 2-year vitamin B treatment on cognitive performance
Zwaluw, N.L. van der; Dhonukshe-Rutten, R.A.M. ; Wijngaarden, J.P. van; Brouwer, E.M. ; Rest, O. van de; Veld, P.H. in 't; Enneman, A.W. ; Dijk, S.C. van; Ham, A.C. ; Swart, K.M.A. ; Velde, N. van der; Schoor, N.M. van; Cammen, T.J.M. van der; Uitterlinden, A.G. ; Lips, P. ; Kessels, R.P.C. ; Groot, C.P.G.M. de - \ 2014
Neurology 83 (2014)23. - ISSN 0028-3878 - p. 2158 - 2166.
folic-acid supplementation - randomized controlled-trial - placebo-controlled trial - alzheimers-disease - elderly-patients - double-blind - homocysteine - metaanalysis - impairment - folate
Objective: We investigated the effects of 2-year folic acid and vitamin B12 supplementation on cognitive performance in elderly people with elevated homocysteine (Hcy) levels. Methods: This multicenter, double-blind, randomized, placebo-controlled trial included 2,919 elderly participants (65 years and older) with Hcy levels between 12 and 50 µmol/L. Participants received daily either a tablet with 400 µg folic acid and 500 µg vitamin B12 (B-vitamin group) or a placebo tablet. Both tablets contained 15 µg vitamin D3. Data were available for global cognitive functioning assessed by Mini-Mental State Examination (n = 2,556), episodic memory (n = 2,467), attention and working memory (n = 759), information processing speed (n = 731), and executive function (n = 721). Results: Mean age was 74.1 (SD 6.5) years. Hcy concentrations decreased 5.0 (95% confidence interval -5.3 to -4.7) µmol/L in the B-vitamin group and 1.3 (-1.6 to -0.9) µmol/L in the placebo group. Cognitive domain scores did not differ over time between the 2 groups, as determined by analysis of covariance. Mini-Mental State Examination score decreased with 0.1 (-0.2 to 0.0) in the B-vitamin group and 0.3 (-0.4 to -0.2) in the placebo group (p = 0.05), as determined by an independent t test. Conclusions: Two-year folic acid and vitamin B12 supplementation did not beneficially affect performance on 4 cognitive domains in elderly people with elevated Hcy levels. It may slightly slow the rate of decline of global cognition, but the reported small difference may be attributable to chance. Classification of evidence: This study provides Class I evidence that 2-year supplementation with folic acid and vitamin B12 in hyperhomocysteinemic elderly people does not affect cognitive performance.
Genomic Characterization of Non-Mucus Adherent Derivatives of Lactobacillus rhamnosus GG Reveals Genes Affecting Pilus Biogenesis
Rasinkangas, P. ; Reunanen, J. ; Douillard, F.P. ; Ritari, J. ; Uotinen, V. ; Palva, A. ; Vos, W.M. de - \ 2014
Applied and Environmental Microbiology 80 (2014)22. - ISSN 0099-2240 - p. 7001 - 7009.
intestinal epithelial-cells - placebo-controlled trial - gram-positive bacteria - functional-analysis - atopic disease - strain gg - adhesion - probiotics - surface - prevention
Lactobacillus rhamnosus GG is one of the best-characterized lactic acid bacteria and can be considered a probiotic paradigm. Comparative and functional genome analysis showed that L. rhamnosus GG harbors a genomic island including the spaCBA-srtC1 gene cluster, encoding the cell surface-decorating host-interacting pili. Here, induced mutagenesis was used to study pilus biogenesis in L. rhamnosus GG. A combination of two powerful approaches, mutation selection and next-generation sequencing, was applied to L. rhamnosus GG for the selection of pilus-deficient mutants from an enriched population. The isolated mutants were first screened by immuno-dot blot analysis using antiserum against pilin proteins. Relevant mutants were selected, and the lack of pili was confirmed by immunoelectron microscopy. The pilosotype of 10 mutant strains was further characterized by analyzing pilin expression using Western blot, dot blot, and immunofluorescence methods. A mucus binding assay showed that the mutants did not adhere to porcine intestinal mucus. Comparative genome sequence analysis using the Illumina MiSeq platform allowed us to determine the nature of the mutations in the obtained pilus-deficient derivatives. Three major classes of mutants with unique genotypes were observed: class I, with mutations in the srtC1 gene; class II, with a deletion containing the spaCBA-srtC1 gene cluster; and class III, with mutations in the spaA gene. Only a limited number of collateral mutations were observed, and one of the pilus-deficient derivatives with a deficient srtC1 gene contained 24 other mutations. This strain, PB12, can be considered a candidate for human trials addressing the impact of the absence of pili.
Intestinal microbiota during early life - impact on health and disease
Nylund, L. ; Satokari, R.M. ; Salminen, S. ; Vos, W.M. de - \ 2014
Proceedings of the Nutrition Society 73 (2014)4. - ISSN 0029-6651 - p. 457 - 469.
human-milk oligosaccharides - placebo-controlled trial - pediatric celiac-disease - infant gut microbiota - formula-fed infants - full-term infants - fecal microbiota - atopic eczema - breast-milk - double-blind
In the first years after birth, the intestinal microbiota develops rapidly both in diversity and complexity while being relatively stable in healthy adults. Different life-style-related factors as well as medical practices have an influence on the early-life intestinal colonisation. We address the impact of some of these factors on the consecutive microbiota development and later health. An overview is presented of the microbial colonisation steps and the role of the host in that process. Moreover, new early biomarkers are discussed with examples that include the association of microbiota and atopic diseases, the correlation of colic and early development and the impact of the use of antibiotics in early life. Our understanding of the development and function of the intestinal microbiota is constantly improving but the long-term influence of early-life microbiota on later life health deserves careful clinical studies.
Taste matters-effects of bypassing oral stimulation on hormone and appetite responses
Spetter, M.S. ; Mars, M. ; Viergever, M.A. ; Graaf, C. de; Smeets, P.A.M. - \ 2014
Physiology and Behavior 137 (2014). - ISSN 0031-9384 - p. 9 - 17.
cephalic phase responses - placebo-controlled trial - sensory-specific satiety - plasma ghrelin levels - food-intake - eating behavior - short-term - circulating ghrelin - energy-intake - c-peptide
The interaction between oral and gastric signals is an important part of food intake regulation. Previous studies suggest that bypassing oral stimulation diminishes the suppression of hunger and increases gastric emptying rate. However, the role of appetite hormones, like cholecystokinin-8 and ghrelin, in this process is still unclear. Our objective was to determine the contributions of gastric and oral stimulation to subsequent appetite and hormone responses and their effect on ad libitum intake. Fourteen healthy male subjects (age 24.6 ± 3.8y, BMI 22.3 ± 1.6 kg/m2) completed a randomized, single-blinded, cross-over experiment with 3 treatment-sessions: 1) Stomach distention: naso-gastric infusion of 500 mL/0 kJ water, 2) Stomach distention with caloric content: naso-gastric infusion of 500 mL/1770 kJ chocolate milk, and 3) Stomach distention with caloric content and oral exposure: oral administration of 500 mL/1770 kJ chocolate milk. Changes in appetite ratings and plasma glucose, insulin, cholecystokinin-8, and active and total ghrelin concentrations were measured at fixed time-points up to 30 min after infusion or oral administration. Subsequently, subjects consumed an ad libitum buffet meal. Oral administration reduced appetite ratings more than both naso-gastric infusions (P <0.0001). Gastric infusion of a caloric load increased insulin and cholecystokinin-8 and decreased total ghrelin concentrations more than ingestion (all P <0.0001). No differences in active ghrelin response were observed between conditions. Ad libitum intake did not differ between oral and gastric administration of chocolate milk (P > 0.05). Thus, gastric infusion of nutrients induces greater appetite hormone responses than ingestion does. These data provide novel and additional evidence that bypassing oral stimulation not only affects the appetite profile but also increases anorexigenic hormone responses, probably driven in part by faster gastric emptying. This confirms the idea that learned associations between sensory characteristics and associated metabolic consequences serve to adapt hormone responses to nutrient content. These findings underscore the importance of oral stimulation in the regulation of food intake.
The effect of a six-month resistance-type exercise training program on the course of high sensitive cardiac troponin T levels in (pre)frail elderly
Linden, N. van der; Tieland, C.A.B. ; Klinkenberg, L.J.J. ; Verdijk, L. ; Groot, C.P.G.M. de; Loon, L.J.C. van; Dieijen-Visser, M.P. ; Meex, S.J.R. - \ 2014
International Journal of Cardiology 175 (2014)2. - ISSN 0167-5273 - p. 374 - 375.
placebo-controlled trial - older-adults - double-blind - biomarkers - frailty - stress - people
Effects of homocysteine lowering with B vitamins on cognitive aging; meta-analysis of 11 trials with cognitive data on 22,000 individuals
Clarke, R. ; Bennett, D. ; Parish, S. ; Eussen, S.J.P.M. ; Groot, C.P.G.M. de - \ 2014
American Journal of Clinical Nutrition 100 (2014)2. - ISSN 0002-9165 - p. 657 - 666.
randomized controlled-trial - folic-acid supplementation - placebo-controlled trial - alzheimers-disease - older-adults - cardiovascular-disease - plasma homocysteine - stroke prevention - vascular-disease - double-blind
Background: Elevated plasma homocysteine is a risk factor for Alzheimer disease, but the relevance of homocysteine lowering to slow the rate of cognitive aging is uncertain. Objective: The aim was to assess the effects of treatment with B vitamins compared with placebo, when administered for several years, on composite domains of cognitive function, global cognitive function, and cognitive aging. Design: A meta-analysis was conducted by using data combined from 11 large trials in 22,000 participants. Domain-based z scores (for memory, speed, and executive function and a domain-composite score for global cognitive function) were available before and after treatment (mean duration: 2.3 y) in the 4 cognitive-domain trials (1340 individuals); Mini-Mental State Examination (MMSE)–type tests were available at the end of treatment (mean duration: 5 y) in the 7 global cognition trials (20,431 individuals). Results: The domain-composite and MMSE-type global cognitive function z scores both decreased with age (mean ± SE: -0.054 ± 0.004 and -0.036 ± 0.001/y, respectively). Allocation to B vitamins lowered homocysteine concentrations by 28% in the cognitive-domain trials but had no significant effects on the z score differences from baseline for individual domains or for global cognitive function (z score difference: 0.00; 95% CI: -0.05, 0.06). Likewise, allocation to B vitamins lowered homocysteine by 26% in the global cognition trials but also had no significant effect on end-treatment MMSE-type global cognitive function (z score difference: -0.01; 95% CI: -0.03, 0.02). Overall, the effect of a 25% reduction in homocysteine equated to 0.02 y (95% CI: -0.10, 0.13 y) of cognitive aging per year and excluded reductions of >1 mo per year of treatment. Conclusion: Homocysteine lowering by using B vitamins had no significant effect on individual cognitive domains or global cognitive function or on cognitive aging.
Systematic review using meta-analyses to estimate dose-response relationships between iodine intake and biomarkers of iodine status in different population groups
Ristic-Medic, D. ; Dullemeijer, C. ; Tepsic, J. ; Petrovic-Oggiano, G. ; Popovic, Z. ; Arsic, A. ; Glibetic, M. ; Souverein, O.W. ; Collings, R. ; Cavelaars, A.J.E.M. ; Groot, C.P.G.M. de; Veer, P. van 't; Gurinovic, M. - \ 2014
Nutrition Reviews 72 (2014)3. - ISSN 0029-6643 - p. 143 - 161.
oral iodized oil - blood spot thyroglobulin - placebo-controlled trial - school-age-children - poppy seed oil - thyroid-function - endemic goiter - urinary iodine - dietary iodine - pregnant-women
The objective of this systematic review was to identify studies investigating iodine intake and biomarkers of iodine status, to assess the data of the selected studies, and to estimate dose-response relationships using meta-analysis. All randomized controlled trials, prospective cohort studies, nested case-control studies, and cross-sectional studies that supplied or measured dietary iodine and measured iodine biomarkers were included. The overall pooled regression coefficient (ß) and the standard error of ß were calculated by random-effects meta-analysis on a double-log scale, using the calculated intake-status regression coefficient (ß) for each individual study. The results of pooled randomized controlled trials indicated that the doubling of dietary iodine intake increased urinary iodine concentrations by 14% in children and adolescents, by 57% in adults and the elderly, and by 81% in pregnant women. The dose-response relationship between iodine intake and biomarkers of iodine status indicated a 12% decrease in thyroid-stimulating hormone and a 31% decrease in thyroglobulin in pregnant women. The model of dose-response quantification used to describe the relationship between iodine intake and biomarkers of iodine status may be useful for providing complementary evidence to support recommendations for iodine intake in different population groups.
The effects of probiotics on barrier function and mucosal pouch microbiota during maintenance treatment for severe pouchitis in patients with ulcerative colitis
Persborn, M. ; Gerritsen, J. ; Wallon, C. ; Carlsson, A. ; Akkermans, L.M.A. ; Soderholm, J.D. - \ 2013
Alimentary Pharmacology and Therapeutics 38 (2013)7. - ISSN 0269-2813 - p. 772 - 783.
placebo-controlled trial - familial adenomatous polyposis - follicle-associated epithelium - lactobacillus-rhamnosus gg - bacterial-infection rates - double-blind trial - anal-anastomosis - macromolecular permeability - maintaining remission - escherichia-coli
Background A total of 10-15% of patients with an ileoanal pouch develop severe pouchitis necessitating long-term use of antibiotics or pouch excision. Probiotics reduce the risk of recurrence of pouchitis, but mechanisms behind these effects are not fully understood. Aim To examine mucosal barrier function in pouchitis, before and after probiotic supplementation and to assess composition of mucosal pouch microbiota. Methods Sixteen patients with severe pouchitis underwent endoscopy with biopsies of the pouch on three occasions: during active pouchitis; clinical remission by 4 weeks of antibiotics; after 8 weeks of subsequent probiotic supplementation (Ecologic 825, Winclove, Amsterdam, the Netherlands). Thirteen individuals with a healthy ileoanal pouch were sampled once as controls. Ussing chambers were used to assess transmucosal passage of Escherichia coli K12, permeability to horseradish peroxidase (HRP) and Cr-51-EDTA. Composition and diversity of the microbiota was analysed using Human Intestinal Tract Chip. Results Pouchitis Disease Activity Index (PDAI) was significantly improved after antibiotic and probiotic supplementation. Escherichia coli K12 passage during active pouchitis [3.7 (3.4-8.5); median (IQR)] was significantly higher than in controls [1.7 (1.0-2.4); P <0.01], did not change after antibiotic treatment [5.0 (3.3-7.1); P = ns], but was significantly reduced after subsequent probiotic supplementation [2.2 (1.7-3.3); P <0.05]. No significant effects of antibiotics or probiotics were observed on composition of mucosal pouch microbiota; however, E. coli passage correlated with bacterial diversity (r = -0.40; P = 0.018). Microbial groups belonging to Bacteroidetes and Clostridium clusters IX, XI and XIVa were associated with healthy pouches. Conclusions Probiotics restored the mucosal barrier to E. coli and HRP in patients with pouchitis, a feasible factor in prevention of recurrence during maintenance treatment. Restored barrier function did not translate into significant changes in mucosal microbiota composition, but bacterial diversity correlated with barrier function.
Comparative genomic and functional analysis of 100 Lactobacillus rhamnosus strains and their comparison with strain GG
Douillard, F.P. ; Ribbera, A. ; Kant, R. ; Pietilä, T.E. ; Järvinen, H.M. ; Messing, M. ; Randazzo, C.L. ; Paulin, L. ; Laine, P.K. ; Ritari, J. ; Caggia, C. ; Lähteinen, T. ; Brouns, S.J.J. ; Satokari, R.M. ; Ossowski, I. von; Reunanen, J. ; Palva, A. ; Vos, W.M. de - \ 2013
Plos Genetics 9 (2013)8. - ISSN 1553-7404
lactic-acid bacteria - intestinal epithelial-cells - placebo-controlled trial - streptococcus-thermophilus - species identification - salmonella-typhimurium - gastrointestinal-tract - adaptive immunity - atopic disease - in-vitro
Lactobacillus rhamnosus is a lactic acid bacterium that is found in a large variety of ecological habitats, including artisanal and industrial dairy products, the oral cavity, intestinal tract or vagina. To gain insights into the genetic complexity and ecological versatility of the species L. rhamnosus, we examined the genomes and phenotypes of 100 L. rhamnosus strains isolated from diverse sources. The genomes of 100 L. rhamnosus strains were mapped onto the L. rhamnosus GG reference genome. These strains were phenotypically characterized for a wide range of metabolic, antagonistic, signalling and functional properties. Phylogenomic analysis showed multiple groupings of the species that could partly be associated with their ecological niches. We identified 17 highly variable regions that encode functions related to lifestyle, i.e. carbohydrate transport and metabolism, production of mucus-binding pili, bile salt resistance, prophages and CRISPR adaptive immunity. Integration of the phenotypic and genomic data revealed that some L. rhamnosus strains possibly resided in multiple niches, illustrating the dynamics of bacterial habitats. The present study showed two distinctive geno-phenotypes in the L. rhamnosus species. The geno-phenotype A suggests an adaptation to stable nutrient-rich niches, i.e. milk-derivative products, reflected by the alteration or loss of biological functions associated with antimicrobial activity spectrum, stress resistance, adaptability and fitness to a distinctive range of habitats. In contrast, the geno-phenotype B displays adequate traits to a variable environment, such as the intestinal tract, in terms of nutrient resources, bacterial population density and host effects
Review article: the role of gastrointestinal hormones in the treatment of delayed gastric emptying in critically ill patients
Luttikhold, J. ; Ruijter, F.M. de; Norren, K. van; Diamant, M. ; Witkamp, R.F. ; Leeuwen, P.A.M. ; Vermeulen, M.A.R. - \ 2013
Alimentary Pharmacology and Therapeutics 38 (2013)6. - ISSN 0269-2813 - p. 573 - 583.
glucagon-like peptide-1 - motilin receptor agonist - placebo-controlled trial - early enteral nutrition - body-weight gain - diabetic gastroparesis - pancreatic-polypeptide - double-blind - food-intake - acid-secretion
Background The role of diet in inflammatory bowel disease (IBD) is supported by migration studies and increasing incidences in line with Westernisation. Aim To give a complete overview of studies associating habitual diet with the onset or relapses in ulcerative colitis (UC) or Crohn's disease (CD). Methods A structured search in Pubmed, the Cochrane Library and EMBASE was performed using defined key words, including only full text papers in English language. Results Forty-one studies were identified, investigating onset (n = 35), relapses (n = 5) or both (n = 1). Several studies reported high intake of sugar or sugar-containing foods (n = 7 UC, n = 12 CD), and low intake of fruits and/or vegetables (n = 5 UC, n = 10 CD) to be associated with an increased onset risk. However, these findings could not be confirmed by similar or higher numbers of other studies. A possible protective role was found for grain-derived products in CD onset, but results were inconsistent for dietary fibre in UC and CD and grain-derived products in UC. No definite conclusions could be drawn for unsaturated fatty acids (UFA), protein and energy intake due to limited and/or inconsistent results. Six studies reported on diet and relapse risk, of which only two (n = 1 UC, n = 1 CD) had a prospective follow-up. Conclusions The current evidence is not sufficient to draw firm conclusions on the role of specific food components or nutrients in the aetiology of IBD. Furthermore, large prospective studies into the role of habitual diet as a trigger of relapses are needed, to identify new therapeutic or preventive targets
Challenges in translational research on probiotic lactobacilli: from in vitro assays to clinical trials
Meijerink, M. ; Mercenier, A.M.E. ; Wells, J. - \ 2013
Beneficial Microbes 4 (2013)1. - ISSN 1876-2883 - p. 83 - 100.
placebo-controlled trial - lactic-acid bacteria - regulatory t-cells - blood mononuclear-cells - intestinal epithelial-cells - irritable-bowel-syndrome - influenza-virus infection - randomized controlled-trial - tight junction proteins - host-microbiota dialog
Beneficial effects of certain probiotic strains have been established in the treatment and prevention of various immune and intestinal disorders in humans, including allergic diseases, chronic inflammatory diseases and diarrhoea. The proposed mechanisms underlying the immunomodulatory effects of probiotics in humans are not understood in precise detail but include enhancement of intestinal barrier function, altered epithelial signalling, competition with pathogens and effects on immune cells and immunity depending on the probiotic strain. The publication of controversial or inconclusive probiotic studies in humans highlights the need for a better understanding of the mechanisms and improved strain selection criteria. This review focuses on the immunomodulatory properties of lactobacilli and bifidobacteria in vitro and in vivo, current knowledge concerning the mechanisms in vivo and challenges in translational research on probiotics. A better understanding of the molecular mechanisms of probiotics, the effect of probiotic mixtures versus single strains, the effect of formulation of probiotics and the fate of ingested probiotics should help to clarify the value of immune assays as selection criteria for probiotics.
The Impact of Lactobacillus plantarum WCFS1 Teichoic Acid D-Alanylation on the Generation of Effector and Regulatory T-cells in Healthy Mice
Smelt, M.J. ; Haan, B.J. de; Bron, P.A. ; Swam, I. van; Meijerink, M. ; Wells, J. ; Kleerebezem, M. ; Faas, M.M. ; Vos, P. de - \ 2013
PLoS ONE 8 (2013)4. - ISSN 1932-6203 - 14 p.
placebo-controlled trial - inflammatory-bowel-disease - blood mononuclear-cells - tlr signaling pathways - lipoteichoic acid - double-blind - dendritic cells - ulcerative-colitis - maintaining remission - acidophilus deficient
To date it remains unclear how probiotics affect the immune system. Bacterial envelope components may play an essential role, as these are the first to establish bacterial-host cell interactions. Teichoic acids (TAs), and especially lipoteichoic acids, are the most pro-inflammatory components of the gram-positive bacterial envelope. This effect is dependent on D-alanyl substitution of the TA backbone and interactions with TLR2 on host cells. Although the pro-inflammatory properties of TAs have been established in vitro, it remains unclear how TAs affect immunomodulation in vivo. In this study, we investigated the role of TA D-alanylation on L. plantarum–induced intestinal and systemic immunomodulation in vivo. For this, we compared the effect of L. plantarum WCFS1 and its TA D-Alanylation negative derivative (dltX-D) on the distribution of dendritic cell and T cell populations and responses in healthy mice. We demonstrated that the majority of the L. plantaruminduced in vivo immunomodulatory effects were dependent on D-alanylation (D-Ala), as some L. plantarum WCFS1-induced immune changes were not observed in the dltX-D-treated group and some were only observed after treatment with dltX-D. Strikingly, not only pro-inflammatory immune responses were abolished in the absence of D-Ala substitution, but also antiinflammatory responses, such as the L. plantarum-induced generation of regulatory T cells in the spleen. With this study we provide insight in host-microbe interactions, by demonstrating the involvement of D-alanylation of TAs on the bacterial membrane in intestinal and systemic immunomodulation in healthy mice.
Effect of iron intervention on growth during gestation, infancy, childhood, and adolescence: a systematic review with meta-analysis
Vucic, V. ; Berti, C. ; Vollhardt, C. ; Fekete, K. ; Cetin, I. ; Koletzko, B. ; Gurinovic, M. ; Veer, P. van 't - \ 2013
Nutrition Reviews 71 (2013)6. - ISSN 0029-6643 - p. 386 - 401.
randomized controlled-trial - breast-fed infants - placebo-controlled trial - anemic school-children - zinc supplementation - micronutrient status - physical growth - cognitive-development - preschool-children - indonesian infants
To evaluate the effect of iron intervention on physical growth in fetuses, infants, children, and adolescents up to 18 years of age, a systematic review with meta-analysis of randomized controlled trials (RCTs) was conducted. Structured electronic searches were conducted to February 2010 using MEDLINE, Embase, and the Cochrane Library databases. RCTs that included iron-fortified foods, iron-fortified formula, or iron supplements and in which height, weight, mid-arm circumference (MAC), head circumference, birth weight, or length of gestation was evaluated were analyzed for inclusion. In total, 21 RCTs in infants, children, and adolescents and 7 studies in pregnant women met the inclusion criteria. The overall pooled result (random-effects model) showed no significant effects of iron intervention on any of the parameters measured. To accommodate wide heterogeneity, studies were stratified according to dose of iron, duration of intervention, age, and baseline iron status. However, only doses of 40–66¿mg of supplemental iron and intervention in children =6 years of age showed a slight but significant association with weight and MAC.
Serum 25-hydroxyvitamin D is associated with cognitive executive function in Dutch prefrail and frail elderly: a cross-sectional study exploring the associations of 25-hydroxyvitamin D with glucose metabolism, cognitive performance and depression
Brouwer, E.M. ; Nieuwerth-van de Rest, O. ; Tieland, C.A.B. ; Zwaluw, N.L. van der; Steegenga, W.T. ; Adam, J.J. ; Loon, L.J.C. van; Feskens, E.J.M. ; Groot, C.P.G.M. de - \ 2013
Journal of the American Medical Directors Association 14 (2013)1. - ISSN 1525-8610 - p. 852.e9 - 852.e17.
randomized controlled-trial - vitamin-d supplementation - placebo-controlled trial - parathyroid-hormone - insulin-resistance - double-blind - older women - risk-factors - us adults - population
Objectives: The primary objective was to explore the possible association of serum 25-hydroxyvitamin D (25[OH] D) and vitamin D intake with markers of glucose metabolism, depression, and cognitive performance. In addition, we examined to what extent the associations between vitamin D and cognitive performance were modified or mediated by fasting plasma glucose (FPG) levels. Design, Setting, and Participants: Cross-sectional study using data of 127 frail or prefrail Dutch elderly, aged 65 years or older. Frailty was defined according to the criteria of Fried and colleagues. A participant was classified prefrail when 1 to 2 criteria were met; frailty was classified as the presence of 3 or more criteria. Measurements: Associations of 25(OH) D and vitamin D intake with markers of glucose metabolism and domain-specific cognitive performance were examined by multivariable regression analyses. The possible association of vitamin D with depression and global cognitive performance was explored by Poisson regression. Results: No associations were observed for 25(OH) D with FPG, fasting plasma insulin (FPI), Homeostasis Model Assessment-estimated Insulin Resistance (HOMA-IR), or depression. In contrast, serum 25(OH) D was positively associated with executive functioning (beta 0.007, P=.01) and tended to be associated with information-processing speed (beta 0.006, P=.06). FPG did not modify or mediate these associations. Vitamin D intake was not associated with cognitive performance, glucose metabolism, or depression. Conclusion: This cross-sectional study suggests an association of serum 25(OH) D with domain-specific cognitive performance, in particular executive functioning and possibly information-processing speed, but not with FPG, FPI, HOMA-IR, or depression. Whether these associations are causal is yet to be demonstrated. Copyright (C) 2013 - American Medical Directors Association, Inc.
Microarray analysis reveals marked intestinal microbiota aberrancy in infants having eczema compared to healthy children in at-risk for atopic disease
Nylund, L. ; Satokari, R. ; Nikkilä, J. ; Rajilic-Stojanovic, M. ; Kalliomäki, M. ; Isolauri, E. ; Salminen, S. ; Vos, W.M. de - \ 2013
BMC Microbiology 13 (2013). - ISSN 1471-2180
placebo-controlled trial - gut microbiota - phylogenetic microarray - double-blind - fecal microbiota - galacto-oligosaccharides - gastrointestinal-tract - molecular analysis - primary prevention - immunoglobulin-e
BACKGROUND: Deviations in composition and diversity of intestinal microbiota in infancy have been associated with both the development and recurrence of atopic eczema. Thus, we decided to use a deep and global microarray-based method to characterize the diversity and temporal changes of the intestinal microbiota in infancy and to define specific bacterial signatures associated with eczema. Faecal microbiota at 6 and 18 months of age were analysed from 34 infants (15 with eczema and 19 healthy controls) selected from a prospective follow-up study based on the availability of faecal samples. The infants were originally randomized to receive either Lactobacillus rhamnosus GG or placebo. RESULTS: Children with eczema harboured a more diverse total microbiota than control subjects as assessed by the Simpson's reciprocal diversity index of the microarray profiles. Composition of the microbiota did not differ between study groups at age of 6 months, but was significantly different at age of 18 months as assessed by MCPP (p=0.01). At this age healthy children harboured 3 -fold greater amount of members of the Bacteroidetes (p=0.01). Microbiota of children suffering from eczema had increased abundance of the Clostridium clusters IV and XIVa, which are typically abundant in adults. Probiotic Lactobacillus rhamnosus GG supplementation in early infancy was observed to have minor long-term effects on the microbiota composition. CONCLUSION: A diverse and adult-type microbiota in early childhood is associated with eczema and it may contribute to the perpetuation of eczema
Intestinal microbiota in functional bowel disorders: a Rome foundation report
Simrén, M. ; Barbara, G. ; Flint, H.J. ; Spiegel, B.M. ; Spiller, R.C. ; Vanner, S. ; Verdu, E.F. ; Whorwell, P.J. ; Zoetendal, E.G. - \ 2013
Gut 62 (2013)1. - ISSN 0017-5749 - p. 159 - 176.
quality-of-life - randomized controlled-trial - placebo-controlled trial - chain fatty-acids - 16s ribosomal-rna - multispecies probiotic supplementation - induced visceral hypersensitivity - postinfective gut dysfunction - mucosa-associated microbiota - human col
It is increasingly perceived that gut host-microbial interactions are important elements in the pathogenesis of functional gastrointestinal disorders (FGID). The most convincing evidence to date is the finding that functional dyspepsia and irritable bowel syndrome (IBS) may develop in predisposed individuals following a bout of infectious gastroenteritis. There has been a great deal of interest in the potential clinical and therapeutic implications of small intestinal bacterial overgrowth in IBS. However, this theory has generated much debate because the evidence is largely based on breath tests which have not been validated. The introduction of culture-independent molecular techniques provides a major advancement in our understanding of the microbial community in FGID. Results from 16S rRNA-based microbiota profiling approaches demonstrate both quantitative and qualitative changes of mucosal and faecal gut microbiota, particularly in IBS. Investigators are also starting to measure host-microbial interactions in IBS. The current working hypothesis is that abnormal microbiota activate mucosal innate immune responses which increase epithelial permeability, activate nociceptive sensory pathways and dysregulate the enteric nervous system. While we await important insights in this field, the microbiota is already a therapeutic target. Existing controlled trials of dietary manipulation, prebiotics, probiotics, synbiotics and non-absorbable antibiotics are promising, although most are limited by suboptimal design and small sample size. In this article, the authors provide a critical review of current hypotheses regarding the pathogenetic involvement of microbiota in FGID and evaluate the results of microbiota-directed interventions. The authors also provide clinical guidance on modulation of gut microbiota in IBS