Gut Microbiota-Modulated Metabolomic Profiling Shapes the Etiology and Pathogenesis of Autoimmune Diseases

Autoimmunity is a complex and multifaceted process that contributes to widespread functional decline that affects multiple organs and tissues. The pandemic of autoimmune diseases, which are a global health concern, augments in both the prevalence and incidence of autoimmune diseases, including type 1 diabetes, multiple sclerosis, and rheumatoid arthritis. The development of autoimmune diseases is phenotypically associated with gut microbiota-modulated features at the molecular and cellular levels. The etiology and pathogenesis of autoimmune diseases comprise the alterations of immune systems with the innate and adaptive immune cell infiltration into specific organs and the augmented production of proinflammatory cytokines stimulated by commensal microbiota. However, the relative importance and mechanistic interrelationships between the gut microbial community and the immune system during progression of autoimmune diseases are still not well understood. In this review, we describe studies on the profiling of gut microbial signatures for the modulation of immunological homeostasis in multiple inflammatory diseases, elucidate their critical roles in the etiology and pathogenesis of autoimmune diseases, and discuss the implications of these findings for these disorders. Targeting intestinal microbiome and its metabolomic associations with the phenotype of autoimmunity will enable the progress of developing new therapeutic strategies to counteract microorganism-related immune dysfunction in these autoimmune diseases.

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Adiponectin Role in Neurodegenerative Diseases: Focus on Nutrition Review

International Journal of Molecular Sciences ◽

10.3390/ijms21239255 ◽

2020 ◽

Vol 21 (23) ◽

pp. 9255

Author(s):

Rita Polito ◽

Irene Di Meo ◽

Michelangela Barbieri ◽

Aurora Daniele ◽

Giuseppe Paolisso ◽

...

Keyword(s):

Gut Microbiota ◽

Neurodegenerative Diseases ◽

Immune Cell ◽

Inflammatory Diseases ◽

Metabolic Effects ◽

Beneficial Effects ◽

The Central Nervous System ◽

Regulatory Effects ◽

Nutrition Review ◽

Selective Process

Adiponectin is an adipokine produced by adipose tissue. It has numerous beneficial effects. In particular, it improves metabolic effects and glucose homeostasis, lipid profile, and is involved in the regulation of cytokine profile and immune cell production, having anti-inflammatory and immune-regulatory effects. Adiponectin’s role is already known in immune diseases and also in neurodegenerative diseases. Neurodegenerative diseases, such as Alzheimer’s disease and Parkinson’s disease, are a set of diseases of the central nervous system, characterized by a chronic and selective process of neuron cell death, which occurs mainly in relation to oxidative stress and neuroinflammation. Lifestyle is able to influence the development of these diseases. In particular, unhealthy nutrition on gut microbiota, influences its composition and predisposition to develop many diseases such as neurodegenerative diseases, given the importance of the “gut-brain” axis. There is a strong interplay between Adiponectin, gut microbiota, and brain-gut axis. For these reasons, a healthy diet composed of healthy nutrients such as probiotics, prebiotics, polyphenols, can prevent many metabolic and inflammatory diseases such as neurodegenerative diseases and obesity. The special Adiponectin role should be taken into account also, in order to be able to use this component as a therapeutic molecule.

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Kaempferol Alleviates Murine Experimental Colitis by Restoring Gut Microbiota and Inhibiting the LPS-TLR4-NF-κB Axis

Frontiers in Immunology ◽

10.3389/fimmu.2021.679897 ◽

2021 ◽

Vol 12 ◽

Author(s):

Yifan Qu ◽

Xinyi Li ◽

Fengying Xu ◽

Shimin Zhao ◽

Xuemei Wu ◽

...

Keyword(s):

Gut Microbiota ◽

Fecal Microbiota Transplantation ◽

Inflammatory Diseases ◽

Intestinal Barrier ◽

Fluorescein Isothiocyanate ◽

Experimental Colitis ◽

Intestinal Microbiome ◽

Attractive Alternative ◽

Protective Effects ◽

Linear Discriminant

Intestinal microbiota dysbiosis is an established characteristic of ulcerative colitis (UC). Regulating the gut microbiota is an attractive alternative UC treatment strategy, considering the potential adverse effects of synthetic drugs used to treat UC. Kaempferol (Kae) is an anti-inflammatory and antioxidant flavonoid derived from a variety of medicinal plants. In this study, we determined the efficacy and mechanism of action of Kae as an anti-UC agent in dextran sulfate sodium (DSS)-induced colitis mice. DSS challenge in a mouse model of UC led to weight loss, diarrhea accompanied by mucous and blood, histological abnormalities, and shortening of the colon, all of which were significantly alleviated by pretreatment with Kae. In addition, intestinal permeability was shown to improve using fluorescein isothiocyanate (FITC)–dextran administration. DSS-induced destruction of the intestinal barrier was also significantly prevented by Kae administration via increases in the levels of ZO-1, occludin, and claudin-1. Furthermore, Kae pretreatment decreased the levels of IL-1β, IL-6, and TNF-α and downregulated transcription of an array of inflammatory signaling molecules, while it increased IL-10 mRNA expression. Notably, Kae reshaped the intestinal microbiome by elevating the Firmicutes to Bacteroidetes ratio; increasing the linear discriminant analysis scores of beneficial bacteria, such as Prevotellaceae and Ruminococcaceae; and reducing the richness of Proteobacteria in DSS-challenged mice. There was also an evident shift in the profile of fecal metabolites in the Kae treatment group. Serum LPS levels and downstream TLR4-NF-κB signaling were downregulated by Kae supplementation. Moreover, fecal microbiota transplantation from Kae-treated mice to the DSS-induced mice confirmed the effects of Kae on modulating the gut microbiota to alleviate UC. Therefore, Kae may exert protective effects against colitis mice through regulating the gut microbiota and TLR4-related signaling pathways. This study demonstrates the anti-UC effects of Kae and its potential therapeutic mechanisms, and offers novel insights into the prevention of inflammatory diseases using natural products.

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The Central Role of the Gut Microbiota in Chronic Inflammatory Diseases

Journal of Immunology Research ◽

10.1155/2014/689492 ◽

2014 ◽

Vol 2014 ◽

pp. 1-12 ◽

Cited By ~ 79

Author(s):

Caroline Marcantonio Ferreira ◽

Angélica Thomaz Vieira ◽

Marco Aurelio Ramirez Vinolo ◽

Fernando A. Oliveira ◽

Rui Curi ◽

...

Keyword(s):

Immune System ◽

Gut Microbiota ◽

Intestinal Microbiota ◽

Immune Cell ◽

Inflammatory Diseases ◽

Sequencing Analysis ◽

Metagenomic Sequencing ◽

Microbiota Composition ◽

Chronic Inflammatory Diseases ◽

Commensal Microbiota

The commensal microbiota is in constant interaction with the immune system, teaching immune cells to respond to antigens. Studies in mice have demonstrated that manipulation of the intestinal microbiota alters host immune cell homeostasis. Additionally, metagenomic-sequencing analysis has revealed alterations in intestinal microbiota in patients suffering from inflammatory bowel disease, asthma, and obesity. Perturbations in the microbiota composition result in a deficient immune response and impaired tolerance to commensal microorganisms. Due to altered microbiota composition which is associated to some inflammatory diseases, several strategies, such as the administration of probiotics, diet, and antibiotic usage, have been utilized to prevent or ameliorate chronic inflammatory diseases. The purpose of this review is to present and discuss recent evidence showing that the gut microbiota controls immune system function and onset, development, and resolution of some common inflammatory diseases.

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Intestinal Microbiota in Common Chronic Inflammatory Disorders Affecting Children

Frontiers in Immunology ◽

10.3389/fimmu.2021.642166 ◽

2021 ◽

Vol 12 ◽

Author(s):

Anna Torun ◽

Anna Hupalowska ◽

Piotr Trzonkowski ◽

Jaroslaw Kierkus ◽

Beata Pyrzynska

Keyword(s):

Quality Of Life ◽

Immune System ◽

Gut Microbiota ◽

Autoimmune Diseases ◽

Pediatric Population ◽

Genetically Engineered ◽

Intestinal Microbiome ◽

Antigen Receptors ◽

Inflammatory Disorders

The incidence and prevalence rate of chronic inflammatory disorders is on the rise in the pediatric population. Recent research indicates the crucial role of interactions between the altered intestinal microbiome and the immune system in the pathogenesis of several chronic inflammatory disorders in children, such as inflammatory bowel disease (IBD) and autoimmune diseases, such as type 1 diabetes mellitus (T1DM) and celiac disease (CeD). Here, we review recent knowledge concerning the pathogenic mechanisms underlying these disorders, and summarize the facts suggesting that the initiation and progression of IBD, T1DM, and CeD can be partially attributed to disturbances in the patterns of composition and abundance of the gut microbiota. The standard available therapies for chronic inflammatory disorders in children largely aim to treat symptoms. Although constant efforts are being made to maximize the quality of life for children in the long-term, sustained improvements are still difficult to achieve. Additional challenges are the changing physiology associated with growth and development of children, a population that is particularly susceptible to medication-related adverse effects. In this review, we explore new promising therapeutic approaches aimed at modulation of either gut microbiota or the activity of the immune system to induce a long-lasting remission of chronic inflammatory disorders. Recent preclinical studies and clinical trials have evaluated new approaches, for instance the adoptive transfer of immune cells, with genetically engineered regulatory T cells expressing antigen-specific chimeric antigen receptors. These approaches have revolutionized cancer treatments and have the potential for the protection of high-risk children from developing autoimmune diseases and effective management of inflammatory disorders. The review also focuses on the findings of studies that indicate that the responses to a variety of immunotherapies can be enhanced by strategic manipulation of gut microbiota, thus emphasizing on the importance of proper interaction between the gut microbiota and immune system for sustained health benefits and improvement of the quality of life of pediatric patients.

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Gardenia Jasminoides Ameliorates Antibiotic-Associated Aggravation of DNCB-Induced Atopic Dermatitis by Restoring the Intestinal Microbiome Profile

Nutrients ◽

10.3390/nu13041349 ◽

2021 ◽

Vol 13 (4) ◽

pp. 1349

Author(s):

Hyo In Kim ◽

Se Hyang Hong ◽

Seo Yeon Lee ◽

Jin Mo Ku ◽

Min Jeong Kim ◽

...

Keyword(s):

Atopic Dermatitis ◽

Immune Cell ◽

Inflammatory Diseases ◽

Intestinal Microbiome ◽

Serum Cytokine ◽

Microbiome Composition ◽

Gardenia Jasminoides ◽

Histological Damage ◽

Microbiome Profile ◽

Free Environment

The intestinal microbiome is considered one of the key regulators of health. Accordingly, the severity of atopic dermatitis (AD) is mediated by the skin and intestinal microbiome environment. In this study, while evaluating the aggravation in AD symptoms by the antibiotics cocktail (ABX)-induced depletion of the intestinal microbiome, we sought to verify the effect of Gardenia jasminoides (GJ), a medicinal herb used for inflammatory diseases, on AD regarding its role on the intestinal microbiome. To verify the aggravation in AD symptoms induced by the depletion of the intestinal microbiome, we established a novel mouse model by administrating an ABX to create a microbiome-free environment in the intestine, and then applied 2,4-dinitrochlorobenzene (DNCB) to induce an AD-like skin inflammatory response. While ABX treatment aggravated AD-like symptoms, the 2-week administration of GJ improved these pathological changes. DNCB application upregulated immune cell count and serum cytokine expression, which were alleviated by GJ. Moreover, pathological alterations by antibiotics and DNCB, including histological damage of the intestine and the intestinal expression of IL-17, were recovered in GJ-treated mice. The beneficial effect of GJ was due to the restoration of the intestinal microbiome composition. Overall, we suggest GJ as a potential therapeutic agent for AD due to its regulation of the intestinal microbiome.

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Gut microbiota metabolite regulation of host defenses at mucosal surfaces: implication in precision medicine

Precision Clinical Medicine ◽

10.1093/pcmedi/pbz008 ◽

2019 ◽

Vol 2 (2) ◽

pp. 110-119 ◽

Cited By ~ 25

Author(s):

Anthony J Bilotta ◽

Yingzi Cong

Keyword(s):

Gut Microbiota ◽

Precision Medicine ◽

Dietary Fiber ◽

Histone Deacetylase Inhibitors ◽

Immune Cell ◽

Inflammatory Diseases ◽

Short Chain Fatty Acids ◽

Cell Functions ◽

Inflammatory State ◽

And Function

Abstract The gut microbiota has a well-established role in the regulation of host homeostasis. Multiple factors control the composition and function of the microbiota. The westernization of diet, a shift away from nutrient-dense foods toward diets high in saturated fats, has been implicated in the rise of chronic inflammatory diseases such as inflammatory bowel disease (IBD). Diet is critical in the development and maintenance of a healthy microbiome, where dietary fiber (found in the highest amounts in fruits, vegetables, and legumes) is metabolized by the microbiome. In turn, the bacterial metabolites of dietary fiber, short chain fatty acids (SCFAs), regulate gut homeostasis. SCFAs engage G-protein coupled receptors (GPRs) and act as histone deacetylase inhibitors (HDACi) to module epithelial and immune cell functions in the intestines, where they generally promote an anti-inflammatory state. This review highlights the functions of SCFAs and their roles in the pathogenesis of IBD to provide insights into their potential therapeutic application for the treatment of IBD for the purposes of precision medicine.

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Interleukin-24 Immunobiology and Its Roles in Inflammatory Diseases

International Journal of Molecular Sciences ◽

10.3390/ijms23020627 ◽

2022 ◽

Vol 23 (2) ◽

pp. 627

Author(s):

Yajie Zhong ◽

Xuan Zhang ◽

Waipo Chong

Keyword(s):

Autoimmune Diseases ◽

Host Defense ◽

Immune Cells ◽

Immune Cell ◽

Inflammatory Diseases ◽

Immune Cell Infiltration ◽

Receptor Complexes ◽

Complex Functions ◽

Inflammatory Bowel ◽

Multifunctional Cytokine

Interleukin (IL)-24 belongs to the IL-10 family and signals through two receptor complexes, i.e., IL-20RA/IL-20RB and IL-20RB/IL22RA1. It is a multifunctional cytokine that can regulate immune response, tissue homeostasis, host defense, and oncogenesis. Elevation of IL-24 is associated with chronic inflammation and autoimmune diseases, such as psoriasis, rheumatoid arthritis (RA), and inflammatory bowel disease (IBD). Its pathogenicity has been confirmed by inducing inflammation and immune cell infiltration for tissue damage. However, recent studies also revealed their suppressive functions in regulating immune cells, including T cells, B cells, natural killer (NK) cells, and macrophages. The tolerogenic properties of IL-24 were reported in various animal models of autoimmune diseases, suggesting the complex functions of IL-24 in regulating autoimmunity. In this review, we discuss the immunoregulatory functions of IL-24 and its roles in autoimmune diseases.

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Effects of Iron and Zinc Biofortified Foods on Gut Microbiota In Vivo (Gallus gallus): A Systematic Review

Nutrients ◽

10.3390/nu13010189 ◽

2021 ◽

Vol 13 (1) ◽

pp. 189

Author(s):

Mariana Juste Contin Gomes ◽

Hércia Stampini Duarte Martino ◽

Elad Tako

Keyword(s):

Gut Microbiota ◽

Pathogenic Bacteria ◽

Experimental Studies ◽

Gallus Gallus ◽

Intestinal Microbiome ◽

Health Concern ◽

In Vivo Model ◽

Positive Effects ◽

Iron And Zinc

Dietary iron and zinc deficiencies are a global health concern. Bacteria that colonize the gastrointestinal tract depend on minerals to maintain their activities; thus, recent evidence suggests that biofortified foods can modulate the host’s beneficial bacterial taxa. The current review analyzed the research data that linked between iron and zinc biofortified foods and gut microbiota modulation. The data analysis was based on the PRISMA guidelines and the data search was performed at PubMed, Web of Science, Science Direct, and Scopus databases for experimental studies published from January 2010 until December 2020. The five selected studies were conducted in an experimental in vivo model (Gallus gallus). The identified and discussed research showed positive effects of biofortified foods on the composition and function of the gut microbiota. Further, an increase in short chain fatty acids producing bacterial populations as Lactobacillus and Ruminococcus, and a decrease in potentially pathogenic bacteria as Streptococcus, Escherichia, and Enterobacter was identified due to the consumption of biofortified foods. In conclusion, biofortified foods may contribute to improved gut health without increasing the colonization of pathogenic bacteria. The dietary inclusion of approximately 50% of iron/zinc biofortified foods has a significant beneficial effect on the gut microbiota. Additional studies in humans and animal models are warranted to further establish the suggested effects on the intestinal microbiome. PROSPERO (CRD42020184221).

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