Impact of Dietary Flavanols on Microbiota, Immunity and Inflammation in Metabolic Diseases

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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Carvedilol Ameliorates Experimental Atherosclerosis by Regulating Cholesterol Efflux and Exosome Functions

International Journal of Molecular Sciences ◽

10.3390/ijms20205202 ◽

2019 ◽

Vol 20 (20) ◽

pp. 5202 ◽

Cited By ~ 2

Author(s):

Chen ◽

Tsui ◽

Chuang ◽

Chiang ◽

Chen ◽

...

Keyword(s):

Cholesterol Efflux ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Nuclear Factor Κb ◽

Experimental Atherosclerosis ◽

Atherosclerotic Cardiovascular Disease ◽

Beneficial Effects ◽

Abca1 Expression ◽

Density Lipoprotein Receptor ◽

And Function

Carvedilol (Cav), a nonselective β-blocker with α1 adrenoceptor blocking effect, has been used as a standard therapy for coronary artery disease. This study investigated the effects of Cav on exosome expression and function, ATP-binding cassette transporter A1 (ABCA1) expression, and cholesterol efflux that are relevant to the process of atherosclerosis. Human monocytic (THP-1) cell line and human hepatic (Huh-7) cells were treated with Cav, and cholesterol efflux was measured. Exosomes from cell culture medium or mice serum were isolated using glycan-coated recognition beads. Low-density lipoprotein receptor knockout (ldlr−/−) mice were fed with high-fat diet and treated with Cav. Cav accentuated cholesterol efflux and enhanced the expressions of ABCA1 protein and mRNA in both THP-1 and Huh-7 cells. In addition, Cav increased expression and function of exosomal ABCA1 in THP-1 macrophage exosomes. The mechanisms were associated with inhibition of nuclear factor-κB (NF-κB) and protein kinase B (Akt). In hypercholesterolemic ldlr−/− mice, Cav enhanced serum exosomal ABCA1 expression and suppressed atherosclerosis by inhibiting lipid deposition and macrophage accumulation. Cav halts atherosclerosis by enhancing cholesterol efflux and increasing ABCA1 expression in macrophages and in exosomes, possibly through NF-κB and Akt signaling, which provides mechanistic insights regarding the beneficial effects of Cav on atherosclerotic cardiovascular disease.

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Metabolic endotoxemia promotes adipose dysfunction and inflammation in human obesity

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00277.2018 ◽

2019 ◽

Vol 316 (2) ◽

pp. E319-E332 ◽

Cited By ~ 13

Author(s):

Mercedes Clemente-Postigo ◽

Wilfredo Oliva-Olivera ◽

Leticia Coin-Aragüez ◽

Bruno Ramos-Molina ◽

Rosa María Giraldez-Perez ◽

...

Keyword(s):

Metabolic Diseases ◽

In Vitro Assays ◽

Low Grade ◽

Human Obesity ◽

Gene And Protein Expression ◽

And Function ◽

Adipose Dysfunction ◽

High Degree ◽

Metabolic Endotoxemia

Impaired adipose tissue (AT) lipid handling and inflammation is associated with obesity-related metabolic diseases. Circulating lipopolysaccharides (LPSs) from gut microbiota (metabolic endotoxemia), proposed as a triggering factor for the low-grade inflammation in obesity, might also be responsible for AT dysfunction. Nevertheless, this hypothesis has not been explored in human obesity. To analyze the relationship between metabolic endotoxemia and AT markers for lipogenesis, lipid handling, and inflammation in human obesity, 33 patients with obesity scheduled for surgery were recruited and classified according to their LPS levels. Visceral and subcutaneous AT gene and protein expression were analyzed and adipocyte and AT in vitro assays performed. Subjects with obesity with a high degree of metabolic endotoxemia had lower expression of key genes for AT function and lipogenesis ( SREBP1, FABP4, FASN, and LEP) but higher expression of inflammatory genes in visceral and subcutaneous AT than subjects with low LPS levels. In vitro experiments corroborated that LPS are responsible for adipocyte and AT inflammation and downregulation of PPARG, SCD, FABP4, and LEP expression and LEP secretion. Thus, metabolic endotoxemia influences AT physiology in human obesity by decreasing the expression of factors involved in AT lipid handling and function as well as by increasing inflammation.

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Beneficial Effects of Dietary Polyphenols on Gut Microbiota and Strategies to Improve Delivery Efficiency

Nutrients ◽

10.3390/nu11092216 ◽

2019 ◽

Vol 11 (9) ◽

pp. 2216 ◽

Cited By ~ 56

Author(s):

Amit Kumar Singh ◽

Célia Cabral ◽

Ramesh Kumar ◽

Risha Ganguly ◽

Harvesh Kumar Rana ◽

...

Keyword(s):

Gut Microbiota ◽

Clinical Data ◽

Antimicrobial Activities ◽

Dietary Polyphenols ◽

Beneficial Effects ◽

Obesity And Diabetes ◽

Bacterial Quorum Sensing ◽

Health And Disease ◽

Bacterial Quorum ◽

And Function

The human intestine contains an intricate ecological community of dwelling bacteria, referred as gut microbiota (GM), which plays a pivotal role in host homeostasis. Multiple factors could interfere with this delicate balance, including genetics, age, antibiotics, as well as environmental factors, particularly diet, thus causing a disruption of microbiota equilibrium (dysbiosis). Growing evidences support the involvement of GM dysbiosis in gastrointestinal (GI) and extra-intestinal cardiometabolic diseases, namely obesity and diabetes. This review firstly overviews the role of GM in health and disease, then critically reviews the evidences regarding the influence of dietary polyphenols in GM based on preclinical and clinical data, ending with strategies under development to improve efficiency of delivery. Although the precise mechanisms deserve further clarification, preclinical and clinical data suggest that dietary polyphenols present prebiotic properties and exert antimicrobial activities against pathogenic GM, having benefits in distinct disorders. Specifically, dietary polyphenols have been shown ability to modulate GM composition and function, interfering with bacterial quorum sensing, membrane permeability, as well as sensitizing bacteria to xenobiotics. In addition, can impact on gut metabolism and immunity and exert anti-inflammatory properties. In order to overcome the low bioavailability, several different approaches have been developed, aiming to improve solubility and transport of dietary polyphenols throughout the GI tract and deliver in the targeted intestinal regions. Although more research is still needed, particularly translational and clinical studies, the biotechnological progresses achieved during the last years open up good perspectives to, in a near future, be able to improve the use of dietary polyphenols modulating GM in a broad range of disorders characterized by a dysbiotic phenotype.

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Osteoimmunology: Interactions of the Bone and Immune System

Endocrine Reviews ◽

10.1210/er.2007-0038 ◽

2008 ◽

Vol 29 (4) ◽

pp. 403-440 ◽

Cited By ~ 322

Author(s):

Joseph Lorenzo ◽

Mark Horowitz ◽

Yongwon Choi

Keyword(s):

Bone Marrow ◽

Immune System ◽

Immune Cells ◽

Bone Cells ◽

The Other ◽

Organ Systems ◽

Health And Disease ◽

The Many ◽

And Function ◽

Broad Overview

Abstract Bone and the immune system are both complex tissues that respectively regulate the skeleton and the body’s response to invading pathogens. It has now become clear that these organ systems often interact in their function. This is particularly true for the development of immune cells in the bone marrow and for the function of bone cells in health and disease. Because these two disciplines developed independently, investigators in each don’t always fully appreciate the significance that the other system has on the function of the tissue they are studying. This review is meant to provide a broad overview of the many ways that bone and immune cells interact so that a better understanding of the role that each plays in the development and function of the other can develop. It is hoped that an appreciation of the interactions of these two organ systems will lead to better therapeutics for diseases that affect either or both.

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Tolerogenic Dendritic Cells Shape a Transmissible Gut Microbiota that Protects from Metabolic Diseases

10.2337/figshare.14687523 ◽

2021 ◽

Author(s):

Emelyne Lécuyer ◽

Tiphaine Le Roy ◽

Aurélie Gestin ◽

Amélie Lacombe ◽

Catherine Philippe ◽

...

Keyword(s):

Dendritic Cells ◽

Metabolic Diseases ◽

Intestinal Inflammation ◽

Intestinal Barrier ◽

Intestinal Barrier Function ◽

Low Grade ◽

Obesity And Diabetes ◽

Tolerogenic Dendritic Cells ◽

Tolerogenic Function ◽

And Function

Excess of chronic contact between microbial motifs and intestinal immune cells are known to trigger a low-grade inflammation involved in many pathologies such as obesity and diabetes. The important skewing of intestinal adaptive immunity in the context of diet-induced obesity (DIO) is well described but how dendritic cells (DCs) participate to these changes is still poorly documented. To address this question, transgenic mice with enhanced DCs lifespan and immunogenicity (DChBcl-2 mice) are challenged with a high-fat diet. Those mice display resistance to DIO and metabolic alterations. The DIO-resistant phenotype is associated with healthier parameters of intestinal barrier function and lower intestinal inflammation. DChBcl-2 DIO-resistant mice demonstrate a particular increase in tolerogenic DC numbers and function which is associated with strong intestinal IgA, Th17 and T regulatory immune responses. Microbiota composition and function analyses reveal that the DChBcl-2 mice microbiota is characterized by lower immunogenicity and an enhanced butyrate production. Cohousing experiments and fecal microbial transplantations are sufficient to transfer the DIO resistance status to WT mice demonstrating that maintenance of DCs tolerogenic ability sustains a microbiota able to drive DIO resistance. DCs tolerogenic function is revealed as a new potent target in metabolic disease management.

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Tolerogenic Dendritic Cells Shape a Transmissible Gut Microbiota that Protects from Metabolic Diseases

10.1101/2020.10.22.350033 ◽

2020 ◽

Author(s):

Emelyne Lécuyer ◽

Tiphaine Le Roy ◽

Aurélie Gestin ◽

Amélie Lacombe ◽

Catherine Philippe ◽

...

Keyword(s):

Dendritic Cells ◽

Metabolic Diseases ◽

Intestinal Inflammation ◽

Intestinal Barrier ◽

Intestinal Barrier Function ◽

Low Grade ◽

Obesity And Diabetes ◽

Tolerogenic Dendritic Cells ◽

Tolerogenic Function ◽

And Function

ABSTRACTExcess of chronic contact between microbial motifs and intestinal immune cells are known to trigger a low-grade inflammation involved in many pathologies such as obesity and diabetes.The important skewing of intestinal adaptive immunity in the context of diet-induced obesity (DIO) is well described but how dendritic cells (DCs) participate to these changes is still poorly documented. To address this question, transgenic mice with enhanced DCs lifespan and immunogenicity (DChBcl-2 mice), are challenged with a high fat diet.Those mice display resistance to DIO and metabolic alterations. The DIO resistant phenotype is associated with healthier parameters of intestinal barrier function and lower intestinal inflammation. DChBcl-2 DIO-resistant mice demonstrate a particular increase in tolerogenic DC numbers and function which is associated with strong intestinal IgA, Th17 and T regulatory immune responses.Microbiota composition and function analyses reveal that the DChBcl-2 mice microbiota is characterized by a lower immunogenicity and an enhanced butyrate production. Cohousing experiments and fecal microbial transplantations are sufficient to transfer the DIO resistance status to WT mice demonstrating that maintenance of DCs tolerogenic ability sustains a microbiota able to drive DIO resistance. DCs tolerogenic function is revealed as a new potent target in metabolic diseases management.

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The Sleep-Immune Crosstalk in Health and Disease

Physiological Reviews ◽

10.1152/physrev.00010.2018 ◽

2019 ◽

Vol 99 (3) ◽

pp. 1325-1380 ◽

Cited By ~ 118

Author(s):

Luciana Besedovsky ◽

Tanja Lange ◽

Monika Haack

Keyword(s):

Immune System ◽

Sleep Duration ◽

Time Course ◽

Future Research ◽

Low Grade ◽

Immune Functions ◽

Short Sleep Duration ◽

Immune Parameters ◽

Immune System Activation ◽

Health And Disease

Sleep and immunity are bidirectionally linked. Immune system activation alters sleep, and sleep in turn affects the innate and adaptive arm of our body’s defense system. Stimulation of the immune system by microbial challenges triggers an inflammatory response, which, depending on its magnitude and time course, can induce an increase in sleep duration and intensity, but also a disruption of sleep. Enhancement of sleep during an infection is assumed to feedback to the immune system to promote host defense. Indeed, sleep affects various immune parameters, is associated with a reduced infection risk, and can improve infection outcome and vaccination responses. The induction of a hormonal constellation that supports immune functions is one likely mechanism underlying the immune-supporting effects of sleep. In the absence of an infectious challenge, sleep appears to promote inflammatory homeostasis through effects on several inflammatory mediators, such as cytokines. This notion is supported by findings that prolonged sleep deficiency (e.g., short sleep duration, sleep disturbance) can lead to chronic, systemic low-grade inflammation and is associated with various diseases that have an inflammatory component, like diabetes, atherosclerosis, and neurodegeneration. Here, we review available data on this regulatory sleep-immune crosstalk, point out methodological challenges, and suggest questions open for future research.

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Anthocyanins Function as Anti-Inflammatory Agents in a Drosophila Model for Adipose Tissue Macrophage Infiltration

BioMed Research International ◽

10.1155/2018/6413172 ◽

2018 ◽

Vol 2018 ◽

pp. 1-9 ◽

Cited By ~ 8

Author(s):

Alice Valenza ◽

Carola Bonfanti ◽

Maria Enrica Pasini ◽

Paola Bellosta

Keyword(s):

Adipose Tissue ◽

Fruits And Vegetables ◽

Metabolic Diseases ◽

Fat Body ◽

Protective Action ◽

Macrophage Infiltration ◽

Tissue Macrophage ◽

Beneficial Effects ◽

Drosophila Model ◽

Stress Kinase

Epidemiological and preclinical studies have demonstrated that bioactive foods like flavonoids, polyphenolic compounds derived from fruits and vegetables, exert a protective action against obesity, cardiovascular disorders, and Adipocyte Tissue Macrophage infiltration (ATM). All these pathologies are characterized by increase in reactive oxygen species (ROS) and in proinflammatory cytokines that have been shown to favor the migration of immune cells, particularly of macrophages, in metabolically active organs like the liver and adipose tissue, that in Drosophila are constituted by a unique organ: the fat body. This study, using a unique Drosophila model that mimics human ATM, reveals the beneficial effects of flavonoids to reduce tissue inflammation. Our data show that anthocyanin-rich food reduces the number of hemocytes, Drosophila macrophages, infiltrating the fat cells, a process that is associated with reduced production of ROS and reduced activation of the JNK/SAPK p46 stress kinase, suggesting a fundamental function for anthocyanins as antioxidants in chronic inflammation and in metabolic diseases.

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Intestinal Barrier in Human Health and Disease

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph182312836 ◽

2021 ◽

Vol 18 (23) ◽

pp. 12836

Author(s):

Natalia Di Tommaso ◽

Antonio Gasbarrini ◽

Francesca Romana Ponziani

Keyword(s):

Gut Microbiota ◽

Metabolic Diseases ◽

Intestinal Barrier ◽

Leaky Gut ◽

Barrier Dysfunction ◽

Permeable Barrier ◽

Gut Dysbiosis ◽

Health And Disease ◽

And Function ◽

The Relationship

The intestinal mucosa provides a selective permeable barrier for nutrient absorption and protection from external factors. It consists of epithelial cells, immune cells and their secretions. The gut microbiota participates in regulating the integrity and function of the intestinal barrier in a homeostatic balance. Pathogens, xenobiotics and food can disrupt the intestinal barrier, promoting systemic inflammation and tissue damage. Genetic and immune factors predispose individuals to gut barrier dysfunction, and changes in the composition and function of the gut microbiota are central to this process. The progressive identification of these changes has led to the development of the concept of ‘leaky gut syndrome’ and ‘gut dysbiosis’, which underlie the relationship between intestinal barrier impairment, metabolic diseases and autoimmunity. Understanding the mechanisms underlying this process is an intriguing subject of research for the diagnosis and treatment of various intestinal and extraintestinal diseases.

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Nordic Diet and Inflammation—A Review of Observational and Intervention Studies

Nutrients ◽

10.3390/nu11061369 ◽

2019 ◽

Vol 11 (6) ◽

pp. 1369 ◽

Cited By ~ 5

Author(s):

Maria Lankinen ◽

Matti Uusitupa ◽

Ursula Schwab

Keyword(s):

Dietary Patterns ◽

Observational Studies ◽

Fruits And Vegetables ◽

Intervention Studies ◽

Current Evidence ◽

Processed Meat ◽

Low Grade ◽

Inverse Association ◽

Beneficial Effects ◽

Nordic Diet

Low-grade inflammation (LGI) has been suggested to be involved in the development of chronic diseases. Healthy dietary patterns, such as the Mediterranean diet (MD), may decrease the markers of LGI. Healthy Nordic diet (HND) has many similarities with MD, but its effects on LGI are less well known. Both of these dietary patterns emphasize the abundant use of fruits and vegetables (and berries in HND), whole grain products, fish, and vegetable oil (canola oil in HND and olive oil in MD), but restrict the use of saturated fat and red and processed meat. The aim of this narrative review is to summarize the results of studies, which have investigated the associations or effects of HND on the markers of LGI. Altogether, only two publications of observational studies and eight publications of intervention trials were found through the literature search. Both observational studies reported an inverse association between the adherence to HND and concentration of high sensitivity C-reactive protein (hsCRP). A significant decrease in the concentration of hsCRP was reported in two out of four intervention studies measuring hsCRP. Single intervention studies reported the beneficial effects on interleukin 1Ra and Cathepsin S. Current evidence suggests the beneficial effects on LGI with HND, but more carefully controlled studies are needed to confirm the anti-inflammatory effects of the HND.

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