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Impact of Dietary Flavanols on Microbiota, Immunity and Inflammation in Metabolic Diseases.
Martín, MÁ, Ramos, S
Nutrients. 2021;(3)
Abstract
Flavanols are natural occurring polyphenols abundant in fruits and vegetables to which have been attributed to beneficial effects on health, and also against metabolic diseases, such as diabetes, obesity and metabolic syndrome. These positive properties have been associated to the modulation of different molecular pathways, and importantly, to the regulation of immunological reactions (pro-inflammatory cytokines, chemokines, adhesion molecules, nuclear factor-κB [NF-κB], inducible enzymes), and the activity of cells of the immune system. In addition, flavanols can modulate the composition and function of gut microbiome in a prebiotic-like manner, resulting in the positive regulation of metabolic pathways and immune responses, and reduction of low-grade chronic inflammation. Moreover, the biotransformation of flavanols by gut bacteria increases their bioavailability generating a number of metabolites with potential to affect human metabolism, including during metabolic diseases. However, the exact mechanisms by which flavanols act on the microbiota and immune system to influence health and disease remain unclear, especially in humans where these connections have been scarcely explored. This review seeks to summarize recent advances on the complex interaction of flavanols with gut microbiota, immunity and inflammation focus on metabolic diseases.
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2.
Suppression of UV-B stress induced flavonoids by biotic stress: Is there reciprocal crosstalk?
Schenke, D, Utami, HP, Zhou, Z, Gallegos, MT, Cai, D
Plant physiology and biochemistry : PPB. 2019;:53-63
Abstract
Plants respond to abiotic UV-B stress with enhanced expression of genes for flavonoid production, especially the key-enzyme chalcone synthase (CHS). Some flavonoids are antioxidative, antimicrobial and/or UV-B protective secondary metabolites. However, when plants are challenged with concomitant biotic stress (simulated e.g. by the bacterial peptide flg22, which induces MAMP triggered immunity, MTI), the production of flavonoids is strongly suppressed in both Arabidopsis thaliana cell cultures and plants. On the other hand, flg22 induces the production of defense related compounds, such as the phytoalexin scopoletin, as well as lignin, a structural barrier thought to restrict pathogen spread within the host tissue. Since all these metabolites require the precursor phenylalanine for their production, suppression of the flavonoid production appears to allow the plant to focus its secondary metabolism on the production of pathogen defense related compounds during MTI. Interestingly, several flavonoids have been reported to display anti-microbial activities. For example, the plant flavonoid phloretin targets the Pseudomonas syringae virulence factors flagella and type 3 secretion system. That is, suppression of flavonoid synthesis during MTI might have also negative side-effects on the pathogen defense. To clarify this issue, we deployed an Arabidopsis flavonoid mutant and obtained genetic evidence that flavonoids indeed contribute to ward off the virulent bacterial pathogen Pseudomonas syringae pv. tomato (Pst) DC3000. Finally, we show that UV-B attenuates expression of the flg22 receptor FLS2, indicating that there is negative and reciprocal interaction between this abiotic stress and the plant-pathogen defense responses.
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3.
Flavonoids and the gastrointestinal tract: Local and systemic effects.
Oteiza, PI, Fraga, CG, Mills, DA, Taft, DH
Molecular aspects of medicine. 2018;:41-49
Abstract
The gastrointestinal (GI) tract plays a central role in the absorption, distribution, metabolism, and excretion of flavonoids, which ultimately define the health effects of these bioactives. These aspects are modulated by the interactions of flavonoids with other dietary components, environmental factors, the host, and the GI microbiota. Flavonoid can target molecules in the luminal content, the different GI tract cell types, and the microbiota. Importantly, flavonoid actions at the GI tract can have an impact systemically, e.g. on glucose homeostasis, lipid and energy metabolism, or cardiovascular risk factors. The beneficial actions of flavonoids at the GI include their capacity to: i) protect the intestinal epithelium against pharmacological insults and food toxins; ii) modulate the activity of enzymes involved in lipid and carbohydrate absorption; iii) maintain the intestinal barrier integrity; iv) modulate the secretion of gut hormones; v) modulate the GI tract immune system; vi) exert potential anti-colorectal cancer activity; and vii) shape microbiota composition and function. Further understanding of the mechanisms mediating the effects of flavonoids on the intestine (and its microbiota) is of critical importance given the relevance of the GI tract on sustaining overall health and of the widespread recommendations of increasing the intake of plant bioactives.
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4.
Effects of flavonoids on intestinal inflammation, barrier integrity and changes in gut microbiota during diet-induced obesity.
Gil-Cardoso, K, Ginés, I, Pinent, M, Ardévol, A, Blay, M, Terra, X
Nutrition research reviews. 2016;(2):234-248
Abstract
Diet-induced obesity is associated with low-grade inflammation, which, in most cases, leads to the development of metabolic disorders, primarily insulin resistance and type 2 diabetes. Although prior studies have implicated the adipose tissue as being primarily responsible for obesity-associated inflammation, the latest discoveries have correlated impairments in intestinal immune homeostasis and the mucosal barrier with increased activation of the inflammatory pathways and the development of insulin resistance. Therefore, it is essential to define the mechanisms underlying the obesity-associated gut alterations to develop therapies to prevent and treat obesity and its associated diseases. Flavonoids appear to be promising candidates among the natural preventive treatments that have been identified to date. They have been shown to protect against several diseases, including CVD and various cancers. Furthermore, they have clear anti-inflammatory properties, which have primarily been evaluated in non-intestinal models. At present, a growing body of evidence suggests that flavonoids could exert a protective role against obesity-associated pathologies by modulating inflammatory-related cellular events in the intestine and/or the composition of the microbiota populations. The present paper will review the literature to date that has described the protective effects of flavonoids on intestinal inflammation, barrier integrity and gut microbiota in studies conducted using in vivo and in vitro models.
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5.
Flavonoid-membrane interactions: involvement of flavonoid-metal complexes in raft signaling.
Tarahovsky, YS, Kim, YA, Yagolnik, EA, Muzafarov, EN
Biochimica et biophysica acta. 2014;(5):1235-46
Abstract
Flavonoids are polyphenolic compounds produced by plants and delivered to the human body through food. Although the epidemiological analyses of large human populations did not reveal a simple correlation between flavonoid consumption and health, laboratory investigations and clinical trials clearly demonstrate the effectiveness of flavonoids in the prevention of cardiovascular, carcinogenic, neurodegenerative and immune diseases, as well as other diseases. At present, the abilities of flavonoids in the regulation of cell metabolism, gene expression, and protection against oxidative stress are well-known, although certain biophysical aspects of their functioning are not yet clear. Most flavonoids are poorly soluble in water and, similar to lipophilic compounds, have a tendency to accumulate in biological membranes, particularly in lipid rafts, where they can interact with different receptors and signal transducers and influence their functioning through modulation of the lipid-phase behavior. In this study, we discuss the enhancement in the lipophilicity and antioxidative activity of flavonoids after their complexation with transient metal cations. We hypothesize that flavonoid-metal complexes are involved in the formation of molecular assemblies due to the facilitation of membrane adhesion and fusion, protein-protein and protein-membrane binding, and other processes responsible for the regulation of cell metabolism and protection against environmental hazards.
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6.
Effects of a flavonoid-rich juice on inflammation, oxidative stress, and immunity in elite swimmers: a metabolomics-based approach.
Knab, AM, Nieman, DC, Gillitt, ND, Shanely, RA, Cialdella-Kam, L, Henson, DA, Sha, W
International journal of sport nutrition and exercise metabolism. 2013;(2):150-60
Abstract
The effects of a flavonoid-rich fresh fruit and vegetable juice (JUICE) on chronic resting and postexercise inflammation, oxidative stress, immune function, and metabolic profiles (metabolomics analysis, gas-chromatography mass-spectrometry platform) in elite sprint and middle-distance swimmers were studied. In a randomized, crossover design with a 3-wk washout period, swimmers (n = 9) completed 10-d training with or without 16 fl oz of JUICE (230 mg flavonoids) ingested pre- and postworkout. Blood samples were taken presupplementation, post-10-d supplementation, and immediately postexercise, with data analyzed using a 2 × 3 repeated-measures ANOVA. Prestudy blood samples were also acquired from nonathletic controls (n = 7, age- and weight-matched) and revealed higher levels of oxidative stress in the swimmers, no differences in inflammation or immune function, and a distinct separation in global metabolic scores (R2Y [cum] = .971). Swim workouts consisted of high-intensity intervals (1:1, 1:2 swim-to-rest ratio) and induced little inflammation, oxidative stress, or immune changes. A distinct separation in global metabolic scores was found pre- to postexercise (R2Y [cum] = .976), with shifts detected in a small number of metabolites related to substrate utilization. No effect of 10-d JUICE was found on chronic resting levels or postexercise inflammation, oxidative stress, immune function, and shifts in metabolites. In conclusion, sprint and middle-distance swimmers had a slight chronic elevation in oxidative stress compared with nonathletic controls, experienced a low magnitude of postworkout perturbations in the biomarkers included in this study, and received no apparent benefit other than added nutrient intake from ingesting JUICE pre- and postworkout for 10 days.
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7.
Regulatory effects of a fermented food concentrate on immune function parameters in healthy volunteers.
Schoen, C, Schulz, A, Schweikart, J, Schütt, S, von Baehr, V
Nutrition (Burbank, Los Angeles County, Calif.). 2009;(5):499-505
Abstract
OBJECTIVE Nutrition is known to influence the immune system and can thereby modulate resistance to infection. The objective of this clinical trial was to assess the influence of a cascade-fermented food consisting of fruits, nuts, and vegetables rich in polyphenols (Regulat) on the immune system in healthy volunteers. METHODS The clinical trial was double-blinded and placebo-controlled. In total, 48 healthy men 20-48 y of age with a body mass index of 20-28 kg/m(2) were enrolled in the clinical trial. The group was characterized according to lifestyle parameters and only men with regular low to moderate intake of fruit and vegetables were enrolled. The intervention lasted for a period of 4 wk. Volunteers received Regulat twice daily or a placebo product (essence of vinegar). RESULTS The intake of Regulat significantly enhanced intracellular glutathione content in lymphocytes (P < 0.05), monocytes (P < 0.05), and natural killer cells (P < 0.01). Furthermore, activation of natural killer cell cytotoxicity in response to interleukin-2 stimulation (P < 0.05), a reduction of total lipid peroxidation, and a reduction of soluble vascular cell adhesion molecule-1 (P < 0.01) and soluble intercellular adhesion molecule-1 (P < 0.05) as inflammatory blood markers were found in the Regulat but not in the placebo group. CONCLUSION In summary, the results from this intervention study demonstrate promising physiologic effects of immune regulation on the innate immune system and antioxidative and anti-inflammatory parameters after Regulat supplementation. However, these promising results need to be confirmed in more volunteers with a more prolonged application to ensure significant beneficial effects of Regulat in the general population.