Autoimmune diseases like rheumatoid arthritis are multifactorial in nature requiring both genetic and environmental factors for onset. hormones in rheumatoid arthritis. 1 INTRODUCTION Autoimmune diseases are characterized by NVP-TNKS656 alterations in normal immune function resulting in hyperactive immune response against self proteins and Rabbit polyclonal to BIK.The protein encoded by this gene is known to interact with cellular and viral survival-promoting proteins, such as BCL2 and the Epstein-Barr virus in order to enhance programed cell death.. tissues. Even though the etiology of autoimmune disorders is usually unknown extensive clinical research over the past decade has pointed to genetic and environmental factors that interact to trigger disease. The genetic basis of autoimmunity is usually associated with a complex array of risk loci the most important being those located in the Major Histocompatibility Complex (MHC) conferring susceptibility or resistance to disease [1]. Different disease outcomes in genetically identical individuals [2] imply that environmental triggers such as diet [3] infections and smoking exacerbate autoimmunity[4-6]. Although in these studies environment-derived antigens have been reported to increase (inflammatory reactions) mechanistic insight into how autoimmunity occurs remain largely obscure. Recent improvements in “omic”-based methods (metagenomics metabolomics and proteomics) and bioinformatics NVP-TNKS656 have facilitated our understanding of the mechanisms of a broad range of diseases and have allowed us to identify potential biomarkers for diagnosis and therapeutic intervention [7]. One particular area of research receiving increasing attention over the past 5 years has focused on using omic-based techniques to study how the gut microbiome the collection of bacteria viruses fungi and protozoa lining the gastrointestinal mucosa significantly impact health and disease [8-10]. These vastly diverse microbial communities not only play a vital role in nutrient synthesis and energy harvest from foods but also tightly regulate the innate and adaptive branches of immunity [11-16]. Recent research about the role of gut microbes in adaptive immune response has substantially changed our understanding of how genes environmental factors and our “second genome” (the gut microbiome) interact to influence autoimmunity. In this review we focus on the sex-bias of autoimmune NVP-TNKS656 disorders that although well documented still lacks mechanistic NVP-TNKS656 insight with regards to genetic and gut microbial interactions. Studies in humans and mouse models have revealed that females are 2-10 occasions more susceptible than males into a wide range of autoimmune disorders including rheumatoid arthritis (RA) Multiple Sclerosis (MS) systemic lupus erythematosus (SLE) myasthenia gravis (MG) Sjogren’s syndrome and Hashimoto’s thyroiditis [17 18 Yet recent evidence is just beginning to emerge linking sex-specific microbial clades during disease progression and pointing to complex interactions between gut microbes genetic factors environment and sex hormones. This review does not intend to discuss the current knowledge around the genetic or environmental triggers of autoimmune disorders and gender-bias which have been elegantly reviewed elsewhere [19-22]. Here we review the current literature relating gut microbes to the sex-based differences observed in numerous autoimmune disorders and discuss how diverse experimental platforms contribute to developing useful NVP-TNKS656 biomarkers for disease progression and for therapeutics. 2 The gut microbiome and autoimmunity Mucosal surfaces are uncovered daily to numerous environmental factors and therefore require an effective protection that can efficiently eliminate the majority of external brokers. The mucosa-associated lymphoid system (MALT) which carries most of the immunologically active cells in the body is the main barrier against potential insults from gut commensals and external agents. A characteristic feature of mucosal immunity that distinguishes it from systemic immunity is the maintenance of tolerance to non-dangerous antigens in the gut [23-26]. Intestinal bacteria are necessary for the development of qualified mucosal immunity. Experiments with germ-free (GF) and specific-pathogen free mice (SPF) have shown that stimuli from intestinal commensals are required for maturation development and function of important components of humoral and cell-mediated immunity [27 28 Bacterial metabolites and metabolic products generated from specific dietary substrates mainly short chain fatty acids (SCFA) also regulate immune function. For.