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Importance of the Microbiota Inhibitory Mechanism on the Warburg Effect in Colorectal Cancer Cells.
Eslami, M, Sadrifar, S, Karbalaei, M, Keikha, M, Kobyliak, NM, Yousefi, B
Journal of gastrointestinal cancer. 2020;(3):738-747
Abstract
METHODS AND RESULTS Colorectal cancer (CRC) is the third most common cancer in the world. Genetic backgrounds, lifestyle, and diet play an important role in CRC risk. The human gut microbiota has an influence on many features of human physiology such as metabolism, nutrient absorption, and immune function. Imbalance of the microbiota has been implicated in many disorders including CRC. It seems Warburg effect hypothesis corresponds to the early beginning of carcinogenesis because of eventual failure in the synthesis of a pyruvate dehydrogenase complex in cooperation with a supply of glucose in carbohydrates rich diets. From investigation among previous publications, we attempted to make it clear importance of Warburg effect in tumors; it also discusses the mechanisms of probiotics in inhibiting tumor progression and reverse Warburg effect of probiotics in modulating the microbiota and CRC therapies. These effects were observed in some clinical trials, the application of probiotics as a therapeutic agent against CRC still requirements further investigation. CONCLUSION Fiber is fermented by colonic bacteria into SCFAs such as butyrate/acetate, which may play a vital role in normal homeostasis by promoting turnover of the colonic epithelium. Butyrate enters the nucleus and functions as a histone deacetylase inhibitor (HDACi). Because cancerous colonocytes undertake the Warburg effect pathway, their favored energy source is glucose instead of butyrate. Therefore, accumulation of moderate concentrations of butyrate in cancerous colonocytes and role as HDACi. Probiotics have been shown to play a protective role against cancer development by modulating intestinal microbiota and immune response.
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An Assessment of the Glyconutrient Ambrotose™ on Immunity, Gut Health, and Safety in Men and Women: A Placebo-Controlled, Double-Blind, Randomized Clinical Trial.
Bloomer, RJ, Butawan, M, van der Merwe, M, Keating, FH
Nutrients. 2020;(6)
Abstract
BACKGROUND Certain dietary fibers have been reported to improve gut health and cellular immunity. Ambrotose is a glyconutrient supplement that contains mannose-rich polysaccharides (acemannan), reported to improve immune function. A more nutrient-dense version of this dietary supplement has been developed recently, with added aloe leaf gel powder (acemannan). The purpose of this study was to evaluate the impact of the traditional and newly developed Ambrotose products on immunity, gut health, and psychological well-being in healthy men and women. METHODS Seventy-five men and women were randomly assigned in double-blind manner to one of five treatments, as follows: Ambrotose Advanced (AA) at 2 or 4 g daily, Ambrotose LIFE (AL) at 2 or 4 g daily, or placebo. Subjects ingested their assigned treatment daily for eight weeks. Resting heart rate, blood pressure, and measures of psychological well-being were analyzed before and after four and eight weeks of supplementation. Blood samples were collected at the same times and analyzed for zonulin, hematology measures, and cytokines-IL-6, IL-10, IL-1β, and TNF-α (analyzed both with and without stimulation via lipopolysaccharide [LPS]). RESULTS All Ambrotose treatments were well-tolerated. There were no differences among treatments in heart rate or blood pressure across time. Self-reported well-being scores were generally higher for the Ambrotose treatments but there were no changes of statistical significance across time (p > 0.05). Differences of statistical significance were noted for select biochemical variables, the most notable being a dramatic decrease in monocytes in the Ambrotose groups. No change was noted in the cytokine response to LPS stimulation in all groups, indicating a maintenance of a healthy immune response. Conclusion: Regular supplementation with Ambrotose is safe and can improve subclinical cellular adversity (as evidenced by a decrease in monocytes), without unnecessary activation of an immune response.
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Rice Components with Immunomodulatory Function.
Toda, M
Journal of nutritional science and vitaminology. 2019;(Supplement):S9-S12
Abstract
Rice (Oryza sativa) is one of the most important food crops in the world, and the effect of its consumption on human health is of great concern. Evidence has accumulated that rice contains several components, such as γ-oryzanol and rice bran fibers, which modulate the immune system. In addition, rice has other immunologically beneficial characteristics. It has a low allergenic potential and is gluten-free, reducing the risk of development of food allergies and diseases related to gluten sensitivity such as coeliac disease. This review presents the recent advances in our understanding of the immunomodulatory function of rice components.
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Nutraceutical functions of beta-glucans in human nutrition.
Ciecierska, A, Drywień, ME, Hamulka, J, Sadkowski, T
Roczniki Panstwowego Zakladu Higieny. 2019;(4):315-324
Abstract
Recent studies have shown that naturally occurring substances found in the food of the daily human diet are important for preventing chronic non-communicable diseases. One of them is beta-glucan, which is a natural polysaccharide, occurring in plant cell walls, mainly oats, barley and wheat. It is also present in baker’s yeast cells, fungal cell walls, and some microorganisms. Beta-glucan belongs to one of the dietary fiber fractions, which are attributed a number of beneficial health properties, including the prevention and treatment of certain digestive diseases and supporting the immune system. This compound has biological activity that depends on the size, molecular weight, conformation, frequency of bonds, solubility and changes in structure. Beta-glucan reduces cholesterol and glucose concentrations in the blood, which reduces the risk of cardiovascular disease and diabetes. In addition to its effects on lipid levels and glucose metabolism, beta-glucan also exhibits antioxidant properties by scavenging reactive oxygen species, thereby reducing the risk of diseases, including atherosclerosis, cardiovascular diseases, neurodegenerative diseases, diabetes, and cancer. Immunostimulatory and antitumor effects have also been reported. The immunostimulatory activity of beta-glucan occurs as a result of its attachment to specific receptors present on the immune cell surface. Beta-glucan belongs to the group of prebiotics which stimulate the growth and activity of the desired natural intestinal microbiota, while inhibiting the growth of pathogens. It plays an important role in the proper functioning of the gastrointestinal tract and preventing inflammation as well as colon cancer. Such a number of health benefits resulting from the properties of beta-glucan may play a key role in improving health and preventing chronic non-communicable diseases, such as diabetes, hypercholesterolemia, obesity, cardiovascular diseases, and cancer.
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Chain length-dependent effects of inulin-type fructan dietary fiber on human systemic immune responses against hepatitis-B.
Vogt, LM, Elderman, ME, Borghuis, T, de Haan, BJ, Faas, MM, de Vos, P
Molecular nutrition & food research. 2017;(10)
Abstract
SCOPE In vivo studies demonstrating that only specific dietary-fibers contribute to immunity are still inconclusive, as measuring immune effects in healthy humans remains difficult. We applied a relatively inefficacious vaccination-challenge to study chain length-dependent effects of inulin-type fructan (ITF) dietary fibers on human immunity. METHODS AND RESULTS ITFs with two different 'degree of polymerization-' (DP)-profiles were tested in vitro for effects on PBMC-cytokines and TLR2 activation. In a double-blind placebo-controlled trial, 40 healthy volunteers (18-29 years) were divided into three groups and supplemented from day 1 to day 14 with DP10-60 ITF, DP2-25 ITF (both n = 13), or fructose placebo (n = 14), 8 g/day. On day 7, all volunteers were vaccinated against hepatitis B. Anti-HbsAg-titer development and lymphocyte subsets were studied. In vitro, DP10-60 ITFs stimulated a Th1-like cytokine profile and stimulated TLR2 more strongly than DP2-25 ITFs. In vivo, DP10-60 increased anti-HBsAg titers, Th1-cells, and transitional B-cells. Both ITFs increased CD45ROhi CTLs at day 35, and CD161+ cytokine producing NK-cells at day 21 and 35. CONCLUSION Support of immunity is determined by the chain length of ITFs. Only long-chain ITFs support immunity against pathogenic hepB-epitopes introduced by vaccination. Our findings demonstrate that specific dietary fibers need to be selected for immunity support.
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A β-Glucan-Based Dietary Fiber Reduces Mast Cell-Induced Hyperpermeability in Ileum From Patients With Crohn's Disease and Control Subjects.
Ganda Mall, JP, Casado-Bedmar, M, Winberg, ME, Brummer, RJ, Schoultz, I, Keita, ÅV
Inflammatory bowel diseases. 2017;(1):166-178
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Abstract
BACKGROUND Administration of β-glucan has shown immune-enhancing effects. Our aim was to investigate whether β-glucan could attenuate mast cell (MC)-induced hyperpermeability in follicle-associated epithelium (FAE) and villus epithelium (VE) of patients with Crohn's disease (CD) and in noninflammatory bowel disease (IBD)-controls. Further, we studied mechanisms of β-glucan uptake and effects on MCs in vitro. METHODS Segments of FAE and VE from 8 CD patients and 9 controls were mounted in Ussing chambers. Effects of the MC-degranulator compound 48/80 (C48/80) and yeast-derived β-1,3/1,6 glucan on hyperpermeability were investigated. Translocation of β-glucan and colocalization with immune cells were studied by immunofluorescence. Caco-2-cl1- and FAE-cultures were used to investigate β-glucan-uptake using endocytosis inhibitors and HMC-1.1 to study effects on MCs. RESULTS β-glucan significantly attenuated MC-induced paracellular hyperpermeability in CD and controls. Transcellular hyperpermeability was only significantly attenuated in VE. Baseline paracellular permeability was higher in FAE than VE in both groups, P<0.05, and exhibited a more pronounced effect by C48/80 and β-glucan P<0.05. No difference was observed between CD and controls. In vitro studies showed increased passage, P<0.05, of β-glucan through FAE-culture compared to Caco-2-cl1. Passage was mildly attenuated by the inhibitor methyl-β-cyclodextrin. HMC-1.1 experiments showed a trend to decreasing MC-degranulation and levels of TNF-α but not IL-6 by β-glucan. Immunofluorescence revealed more β-glucan-uptake and higher percentage of macrophages and dendritic cells close to β-glucan in VE of CD compared to controls. CONCLUSIONS We demonstrated beneficial effects of β-glucan on intestinal barrier function and increased β-glucan-passage through FAE model. Our results provide important and novel knowledge on possible applications of β-glucan in health disorders and diseases characterized by intestinal barrier dysfunction.