epiglucan and Atherosclerosis

We have earlier demonstrated that muesli enriched with oat beta-glucan effectively lowered serum LDL cholesterol. Addition of plant stanols further lowered LDL cholesterol. Besides these hypocholesterolemic effects, beta-glucan and plant stanol esters (PSE) may also affect inflammatory processes. Forty-two mildly hypercholesterolemic subjects randomly consumed for 4 wk (crossover design) control muesli (4.8 g control fiber), beta-glucan muesli (4.8 g oat beta-glucan), or combination muesli (4.8 g oat beta-glucan plus 1.4 g stanol as PSE). Changes in cytokine production (IL-6, IL-8, and TNF-alpha) of LPS-stimulated peripheral blood mononuclear cells (PBMC) and whole blood were evaluated, as well as changes in plasma high-sensitivity (hs)-CRP. Additionally, changes in expression profiles of 84 genes involved in atherosclerosis metabolism were assessed in isolated PBMC. IL-6, IL-8, and TNF-alpha production by PBMC and whole blood after LPS stimulation did not differ between the treatments. Also high-sensitivity C-reactive protein (hs-CRP) levels were similar. beta-Glucan consumption did not change gene expression, while only 3 genes (ADFP, CDH5, CSF2) out of the 84 genes from the atherosclerotic risk panel were differentially expressed (p < 0.05) after consumption of PSE. Consumption of beta-glucan with or without PSE did not influence inflammatory parameters in mildly hypercholesterolemic subjects.

Topics: Adult; Atherosclerosis; Avena; beta-Glucans; C-Reactive Protein; Cross-Over Studies; Dietary Fiber; Double-Blind Method; Female; Gene Expression; Genetic Predisposition to Disease; Humans; Hypercholesterolemia; Inflammation; Interleukin-1; Interleukin-8; Leukocytes, Mononuclear; Lipopolysaccharides; Male; Middle Aged; Sitosterols; Tumor Necrosis Factor-alpha

Pro‑inflammatory (M1) macrophages have key roles in atherogenesis. As β‑glucan has been demonstrated to exert pro‑inflammatory effects, the present study examined whether β‑glucan exerts atherogenic effects via converting macrophages into M1 phenotype. The results from reverse transcription‑quantitative polymerase chain reaction, flow cytometry, western blotting and transmission electron microscope indicated that M1 macrophage markers inducible nitric oxide synthase and cluster of differentiation 80 were upregulated, dectin‑1 (a receptor for β‑glucan) expression and nuclear factor (NF)‑κB nuclear translocation were promoted, and autophagy level was inhibited following β‑glucan treatment of macrophages. Additionally, dectin‑1 small interfering RNA (siRNA), autophagy inducer rapamycin and NF‑κB inhibitor SN50 reversed the effects of β‑glucan on autophagy level and macrophage M1 polarization, suggesting that dectin‑1 and NF‑κB are upstream of autophagy in β‑glucan‑induced macrophage M1 polarization. Notably, simultaneous treatment with dectin‑1 siRNA and SN50 exhibited similar effects on β‑glucan‑reduced autophagy compared with dectin‑1 siRNA treatment alone. These findings demonstrate that dectin‑1 may mediate β‑glucan‑reduced autophagy through NF‑κB in macrophages. Accordingly, results from hematoxylin and eosin staining, western blotting and immunofluorescence staining demonstrated that β‑glucan accelerated the progress of atherosclerosis in apolipoprotein E‑deficient mice and modulated expression of dectin‑1, beclin‑1 and light chain 3II/I in aortas similarly to that observed in macrophages. These results indicate that dectin‑1 activation by β‑glucan exerts atherogenic effects via converting macrophages into M1 phenotype in an NF‑κB‑autophagy‑dependent pathway.

Topics: Animals; Apolipoproteins E; Atherosclerosis; Autophagy; B7-1 Antigen; beta-Glucans; Cell Polarity; Disease Models, Animal; Lectins, C-Type; Macrophages; Male; Mice; Microscopy, Electron, Transmission; NF-kappa B; Nitric Oxide Synthase; RAW 264.7 Cells; Signal Transduction

There is strong evidence indicating that gut microbiota have the potential to modify, or be modified by the drugs and nutritional interventions that we rely upon. This study aims to characterize the compositional and functional effects of several nutritional, neutraceutical, and pharmaceutical cardiovascular disease interventions on the gut microbiome, through metagenomic and metabolomic approaches. Apolipoprotein-E-deficient mice were fed for 24 weeks either high-fat/cholesterol diet alone (control, HFC) or high-fat/cholesterol in conjunction with one of three dietary interventions, as follows: plant sterol ester (PSE), oat β-glucan (OBG) and bile salt hydrolase-active Lactobacillus reuteri APC 2587 (BSH), or the drug atorvastatin (STAT). The gut microbiome composition was then investigated, in addition to the host fecal and serum metabolome.. We observed major shifts in the composition of the gut microbiome of PSE mice, while OBG and BSH mice displayed more modest fluctuations, and STAT showed relatively few alterations. Interestingly, these compositional effects imparted by PSE were coupled with an increase in acetate and reduction in isovalerate (p < 0.05), while OBG promoted n-butyrate synthesis (p < 0.01). In addition, PSE significantly dampened the microbial production of the proatherogenic precursor compound, trimethylamine (p < 0.05), attenuated cholesterol accumulation, and nearly abolished atherogenesis in the model (p < 0.05). However, PSE supplementation produced the heaviest mice with the greatest degree of adiposity (p < 0.05). Finally, PSE, OBG, and STAT all appeared to have considerable impact on the host serum metabolome, including alterations in several acylcarnitines previously associated with a state of metabolic dysfunction (p < 0.05).. We observed functional alterations in microbial and host-derived metabolites, which may have important implications for systemic metabolic health, suggesting that cardiovascular disease interventions may have a significant impact on the microbiome composition and functionality. This study indicates that the gut microbiome-modifying effects of novel therapeutics should be considered, in addition to the direct host effects.

Topics: Acetates; Animals; Apolipoproteins E; Atherosclerosis; Atorvastatin; beta-Glucans; Butyrates; Cardiovascular Diseases; Carnitine; Cholesterol; Cholesterol, Dietary; Diet, High-Fat; Dietary Supplements; Feces; Gastrointestinal Microbiome; Hemiterpenes; Limosilactobacillus reuteri; Male; Metabolome; Mice; Obesity; Pentanoic Acids; Probiotics

Topics: Animals; Atherosclerosis; beta-Glucans; Biomarkers; Blood Glucose; Combined Modality Therapy; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diabetic Nephropathies; Diet, High-Fat; Dietary Fiber; Dietary Supplements; Exercise Therapy; Glycated Hemoglobin; Lipids; Male; Rats, Wistar; Saccharomyces cerevisiae; Streptozocin

Probiotic bacteria have been associated with a reduction in cardiovascular disease risk, a leading cause of death and disability.. The aim of this study was to assess the impact of dietary administration of exopolysaccharide-producing probiotic Lactobacillus cultures on lipid metabolism and gut microbiota in apolipoprotein E (apoE)-deficient mice.. First, we examined lipid metabolism in response to dietary supplementation with recombinant β-glucan-producing Lactobacillus paracasei National Food Biotechnology Centre (NFBC) 338 expressing the glycosyltransferase (Gtf) gene from Pediococcus parvulus 2.6 (GTF), and naturally exopolysaccharide-producing Lactobacillus mucosae Dairy Product Culture Collection (DPC) 6426 (DPC 6426) compared with the non-β-glucan-producing isogenic control strain Lactobacillus paracasei NFBC 338 (PNZ) and placebo (15% wt:vol trehalose). Second, we examined the effects on the gut microbiota of dietary administration of DPC 6426 compared with placebo. Probiotic Lactobacillus strains at 1 × 10(9) colony-forming units/d per animal were administered to apoE(-/-) mice fed a high-fat (60% fat)/high-cholesterol (2% wt:wt) diet for 12 wk. At the end of the study, aortic plaque development and serum, liver, and fecal variables involved in lipid metabolism were analyzed, and culture-independent microbial analyses of cecal content were performed.. Total cholesterol was reduced in serum (P < 0.001; ∼33-50%) and liver (P < 0.05; ∼30%) and serum triglyceride concentrations were reduced (P < 0.05; ∼15-25%) in mice supplemented with GTF or DPC 6426 compared with the PNZ or placebo group, respectively. In addition, dietary intervention with GTF led to increased amounts of fecal cholesterol excretion (P < 0.05) compared with all other groups. Compositional sequencing of the gut microbiota revealed a greater prevalence of Porphyromonadaceae (P = 0.001) and Prevotellaceae (P = 0.001) in the DPC 6426 group and lower proportions of Clostridiaceae (P < 0.05), Peptococcaceae (P < 0.001), and Staphylococcaceae (P < 0.01) compared with the placebo group.. Ingestion of exopolysaccharide-producing lactobacilli resulted in seemingly favorable improvements in lipid metabolism, which were associated with changes in the gut microbiota of mice.

Topics: Animals; Apolipoproteins E; Atherosclerosis; beta-Glucans; Cholesterol; Diet; Dietary Supplements; Disease Models, Animal; Feces; Gastrointestinal Tract; Gene Expression Regulation, Enzymologic; Glycosyltransferases; Lactobacillus; Lipid Metabolism; Liver; Mice; Mice, Knockout; Microbiota; Pediococcus; Probiotics; Triglycerides; Vascular Cell Adhesion Molecule-1

The present study aimed to investigate the effects of separate and simultaneous dietary intake of atorvastatin (ATO) and the soluble fiber oat bran on serum and hepatic lipid levels and the degree of atherosclerosis. Ninety female LDL-receptor-deficient (LDLr-/-) mice were fed a Western-type diet containing either low dose (0.0025%), high dose (0.01%) or no ATO, with or without oat bran (27%) (n=15 per group) for 16 weeks. Both ATO and oat bran were effective in reducing serum total cholesterol levels (low ATO: -5.48, high ATO: -9.12, oat bran: -3.82 mmol/l, compared to control (no ATO/no oat bran), all p<0.0001). When oat bran was added to a low dose ATO, the cholesterol-lowering effects of this combination were 50% smaller compared to the low dose ATO diet alone (between-group difference: 2.77 mmol/l, p=0.002), whereas total cholesterol decreased to a similar extent in the groups fed a high dose ATO, with or without oat bran (between-group difference: 1.10 mmol/l, p=0.21). Serum LDL- and HDL-cholesterol, triglycerides, hepatic lipid levels and atherosclerotic lesion development showed a similar pattern. In conclusion, the efficacy of oat bran and atorvastatin to lower lipid levels and atherosclerosis is reduced after simultaneous intake. We hypothesize that oat bran inhibits the intestinal absorption of atorvastatin, and consequently its cholesterol-lowering effects. The effects are likely dependent on the type of statin and dietary fiber, and on the relative timing of intake of the statin and the dietary fiber. Future studies should focus on these aspects to provide further insight into the exact mechanism of this food-drug interaction.

Topics: Adipose Tissue; Animals; Anticholesteremic Agents; Aorta; Atherosclerosis; Atorvastatin; Avena; beta-Glucans; Blood; Body Weight; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Combined Modality Therapy; Dietary Fiber; Eating; Female; Heptanoic Acids; Intestinal Absorption; Lipids; Liver; Mice; Mice, Inbred Strains; Mice, Knockout; Plaque, Atherosclerotic; Pyrroles; Receptors, LDL; Treatment Outcome; Triglycerides