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The Role of Microbial Byproducts in Protection Against Immunological Disorders and the Hygiene Hypothesis


Vaccine Adjuvant Properties of Probiotic Bacteria

Abstract: Vaccine-preventable diseases are still responsible for the deaths of more than 1 million children under the age of 5 years annually, mostly in developing countries. A substantial number of these deaths are due to pneumococcal bacteria and infections with rotavirus. Important issues faced by the WHO, governments, vaccine manufacturers, and international organizations such as UNICEF and the Global Alliance for Vaccines and Immunization (GAVI) are the cost-effective introduction of these life-saving vaccines in resource-poor countries where there is a considerable disease burden, and achieving high rates of completion of vaccination schedules remains elusive. Problems with vaccine coverage and vaccine delivery in these regions are significant, as in some cases large proportions of the target population do not receive adequate vaccination. Consequently, there is a need to develop more effective vaccination strategies that can provide adequate protection with reduced schedules. To date, emphasis has been placed on identifying novel vaccine antigens and adjuvants that induce stronger protective immune responses, as well as developing mucosally-administered vaccines. These approaches would have enormous benefits in allowing safe administration of vaccines in remote areas and may overcome the necessity for multiple doses. In this regard, the use of probiotic bacteria as novel mucosal adjuvants to enhance existing vaccine specific-immune responses offers an exciting new approach. In this review, we discuss the evidence for the role of probiotics in enhancing vaccine responses and provide justification for further investigation into their clinical effects and mechanisms of action. ... Read more

Does the Gut Microbiota Trigger Hashimoto's Thyroiditis?

Abstract: Hashimoto's thyroiditis is an organ-specific autoimmune disease in which both genetic predisposition and environmental factors serve as the trigger of the disease. A growing body of evidence suggests involvement of viral infection in the development of Hashimoto's thyroiditis. However, not only pathogenic microorganisms but also non-pathogenic commensal microorganisms induce proinflammatory or regulatory immune responses within the host. In accordance, series of studies indicate a critical role of intestinal commensal microbiota in the development of autoimmune diseases including inflammatory bowel diseases, type 1 diabetes, rheumatoid arthritis, and multiple sclerosis. In contrast, the role of the gut and indigenous microorganisms in Hashimoto's thyroiditis has received little attention. Whereas activation of innate pattern recognition receptors such as Toll-like receptors and disturbed intestinal epithelial barrier may contribute to thyroiditis development, only a few studies have addressed a link between the gut and Hashimoto's thyroiditis and provided just indirect and weak evidence for such a link. Despite this unsatisfactory situation, we here focus on the possible interaction between the gut and thyroid autoimmunity. Further studies are clearly needed to test the hypothesis that the gut commensal microflora represents an important environmental factor triggering Hashimoto's thyroiditis. ... Read more

Sublingual Specific Immunotherapy

Abstract: Sublingual application of allergen extracts in specific immunotherapy is a modern approach aimed at improving patient treatment acceptance through reduced serious side effects. This therapeutic approach has proven to be efficacious and safe for the treatment of allergies caused by airborne allergens: 1) studies have shown a rapid onset of action, as early as seven days after beginning treatment; 2) a strong effect during treatment, superior to most forms of symptomatic treatment; 3) a lasting effect after cessation; 4) a preventive effect against new sensitizations and new-onset asthma; and 5) an unprecedented safety profile compared to the subcutaneous route. SLIT is an established treatment option for moderate to severe allergic rhinoconjunctivitis with or without asthma, which can be given to adults as well as to children above five. The complexity of the treatment of this condition mandates expert care by an experienced allergologist. ... Read more

miRNAs at the Crossroad Between Hematopoietic Malignancies and Autoimmune Pathogenesis

Abstract: The study of microRNA (miRNA) regulation in the pathogenesis of autoimmune diseases and hematopoietic malignancies provides new understanding of the mechanisms of disease and is currently the focus of many researchers in the field. Autoimmune disorders and cancers of immune system comprise a wide range of genetically complex diseases that share certain aspects of dysregulated genetic networks, most notably deactivation of apoptosis. miRNA mechanisms control gene expression at the post-transcriptional level, linking mRNA processing and gene function. Considerable amount of data have been accumulated that indicate that the alteration of miRNA expression closely mirrors the development of immune system diseases and is likely to play a role in their pathogenesis. However, a knowledge gap remains in our understanding of how miRNA dysregulation and the specific effects of miRNAs on target gene expression underlay the disease phenotype. Here we review a number of studies describing miRNA alterations in autoimmune diseases and hematopoietic cancers and discuss potential miRNA-regulated mechanisms that differentially influence the development of autoimmunity as compared to cancer progression. ... Read more

Role of the IL-23/IL-17 Axis in Crohn's Disease

Abstract: Crohn's disease is an immune-mediated disease that is characterized by chronic intestinal inflammation. Effector CD4+ T-lymphocytes are expanded in Crohn's disease-associated inflammatory lesions and play a critical role in the pathogenesis of this condition. Recently, a novel population of effector T-lymphocytes has been identified, which is clearly separated from the traditional Th1 and Th2 lineages and is characterized by the secretion of IL-17, hence its designation as Th17. The development of this population has been closely linked to IL-23, a member of the IL-12 family of cytokines. Converging lines of evidence support the hypothesis that the IL-23/Th17 axis is of pathogenic relevance for Crohn's disease. Protein and mRNA levels of IL-23, IL-17, and other Th17 effector cytokines, such as IL-21 and IL-22, are elevated in areas with active Crohn's disease-related inflammation, whereas lamina propria mononuclear cells from patients with Crohn's disease secrete increased amounts of IL-17 upon T-cell receptor-specific stimulation. Genome-wide association studies have identified several Crohn's disease-associated polymorphisms in genes that encode for proteins of the IL-23/Th17 pathway. Functional studies have shown that Th17-related effector cytokines induce pro-inflammatory responses that are components of the pathogenetic mechanisms of Crohn's disease, including recruitment of neutrophils via IL-8 induction, upregulation of inflammatory mediators such as TNF-α, IL-1β, and IL-6, and secretion of metalloproteinases by intestinal fibroblasts. Finally, in several animal models of intestinal inflammation, disease severity is ameliorated when the IL-23/Th17 pathway is rendered deficient. These findings point to a critically important role for IL-23/Th17-mediated immune responses in Crohn's disease pathogenesis and may offer unique therapeutic opportunities for patients. ... Read more

Peanut Allergy: An Evolving Clinical Challenge

Abstract: Peanut allergy is an IgE-mediated food allergy responsible for causing severe and occasionally fatal reactions in those sensitized to peanuts. The prevalence of peanut allergy appears to be on the rise worldwide, yet there are no therapeutics currently available that can alter the course of this condition. This article will review the epidemiology, pathogenesis, and clinical features of peanut allergy and discuss future possibilities in diagnostic and therapeutic modalities. ... Read more

Gut-mediated and HLA-B27-associated Arthritis: An Emphasis on Ankylosing Spondylitis and Crohn's Disease with a Proposal for the Use of New Treatment

Abstract: Ankylosing spondylitis (AS) and Crohn's disease (CD), especially when associated with spondylitis are interrelated conditions included within the categories of spondyloarthropathic disease entities. They share some common clinical, genetic, and microbiological findings. An extensive amount of studies which have been carried out by various independent groups throughout the world have shown that Klebsiella pneumoniae microorganisms could be suggested as the most likely etiopathogenetic triggers for AS and CD based on the molecular mimicry mechanism and the existence of the evidence for immunological, microbiological, and molecular link between Klebsiella and self antigens. It is proposed that the use of low starch diet in conjunction with the currently used treatment might help in the eradication of Klebsiella microbes from the bowel and could result in the stoppage and alleviation of the disease process in patients with AS and/or CD. ... Read more

Cytokines in the Pathogenesis of Ulcerative Colitis

Abstract: Ulcerative colitis is a chronic inflammatory condition of the large intestine whose etiology remains largely unknown. Its pathogenesis involves the breakdown of intestinal mucosal homeostasis due to a genetically determined miscommunication between commensal flora and the gut associated immune system. Cytokines are central components of the inflammatory pathways that take place during the active and chronic phases of ulcerative colitis. Recent research has identified several novel cytokine systems that are upregulated at the mucosa of patients with UC and started to unveil their functional importance for disease pathogenesis. The significance of interleukin-13 (IL-13), TNF-like cytokine 1A (TL1A), IL-33, and their receptors in ulcerative colitis is strongly supported by converging expression and functional data. These molecular systems may define subgroups of patients with uniform immunological profiles. Within these subpopulations such novel cytokine systems may serve as markers of biological activity of the disease. More importantly, they may offer unique therapeutic opportunities through the development of drugs that specifically target and neutralize well-defined inflammatory pathways. ... Read more

T Cell Costimulation and Coinhibition: Genetics and Disease

Abstract: T cell costimulatory and coinhibitory pathways are essential orchestrators and regulators of the adaptive immune response. In recent years, the costimulatory CD28 receptor and B7 ligand families have been expanded to include a total of four and seven members, respectively. Several polymorphisms, mutations, and deletions in both regulatory and protein-coding regions of these genes have subsequently been discovered and evaluated for genetic linkage to various human diseases. Here, we review this evidence as we discuss T cell costimulation and coinhibition in the context of genetic susceptibility to autoimmunity, cancer, and other diseases. As we gain further insight into the functional significance and mechanism of these immunoregulatory pathways by both genetic and immunological approaches, these receptors and ligands are poised to become key targets for immunotherapy. ... Read more

Inflammatory Disease and the Human Microbiome

Abstract: The human body is a superorganism in which thousands of microbial genomes continually interact with the human genome. A range of physical and neurological inflammatory diseases are now associated with shifts in microbiome composition. Seemingly disparate inflammatory conditions may arise from similar disruption of microbiome homeostasis. Intracellular pathogens long associated with inflammatory disease are able to slow the innate immune response by dysregulating activity of the VDR nuclear receptor. This facilitates the ability of other species to gradually accumulate in tissue and blood, where they generate proteins and metabolites that significantly interfere with the body’s metabolic processes. The microbes that contribute to this dysfunction are often inherited from family members. Immunosuppressive therapies for inflammatory disease allow pathogens driving these processes to spread with greater ease. In contrast to immunosuppression, treatments that stimulate the immune system seem to allow for reversal of this pathogen-induced genomic dysregulation. ... Read more

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