Intestinal Microbiota Influences Non-intestinal Related Autoimmune Diseases

Abstract

The human body is colonized by millions of microorganisms named microbiota that interact with our tissues in a cooperative and non-pathogenic manner. These microorganisms are present in the skin, gut, nasal, oral cavities, and genital tract. In fact, it has been described that the microbiota contributes to balancing the immune system to maintain host homeostasis. The gut is a vital organ where microbiota can influence and determine the function of cells of the immune system and contributes to preserve the wellbeing of the individual. Several articles have emphasized the connection between intestinal autoimmune diseases, such as Crohn's disease with dysbiosis or an imbalance in the microbiota composition in the gut. However, little is known about the role of the microbiota in autoimmune pathologies affecting other tissues than the intestine. This article focuses on what is known about the role that gut microbiota can play in the pathogenesis of non-intestinal autoimmune diseases, such as Grave's diseases, multiple sclerosis, type-1 diabetes, systemic lupus erythematosus, psoriasis, schizophrenia, and autism spectrum disorders. Furthermore, we discuss as to how metabolites derived from bacteria could be used as potential therapies for non-intestinal autoimmune diseases.

Keywords: CNS; autoimmune disease; gut; microbiome; microbiota; skin.

Figure 1

Microbiota and pathogen control mechanisms of the gut immune system. The immune system of the gut has to deal with wide diversity of microbiota and pathogens. Thus, the immune system will help to establish a beneficial microbiota composition at the gut. Different mechanisms of the gut immune system have been discovered that control microbiota overgrowth and pathogens invasion. The gut immune system locates in the mucosa layer of the intestine mainly at the epithelium layer and Peyer's patches at the lamina propia. Enterocytes, enteroendocrine cells, globet cells, and Paneth cells, located in the intestinal epithelial layer, secrete antimicrobial peptides like defensins. It has been shown that defensins are produced in the course of innate immune defense to activate the adaptive immune response. Another mechanism to control microbiota is the secretion of IgA which is accomplished by dendritic cells (DC). IgGA by interacting with bacteria impedes their adhesion and inhibits bacteria motility. DCs are localized at mucosal surfaces in antigen uptake sites and at inductive lymphoid tissue; they can directly sampling the normal flora and pathogenic bacteria. In the mesenteric lymph node DCs can promote differentiation of T cells, to regulate immune tolerance. Once T cells are activated they differentiate to T helper cells (Th), like Th1, Th2, or Th17 cells. Intestinal DCs will also regulate the differentiation of T cells to T regulatory (Treg) cells. Treg cells have the capacity to suppress the activation and proliferation of Th cells by the secretion of anti-inflammatory cytokines.

Figure 2

Influence of the gut microbiota in non-intestinal diseases. Gut dysbiosis induced by external factors as diet, infections, or antibiotic overuse lead to an inflammatory response that influence the outcome of several autoimmune diseases as Grave's disease, Hashimoto's Thyroiditis, Multiple Sclerosis, SLE, and type1 diabetes. It has also been observed an important role in skin related autoimmune diseases as Psoriasis. Moreover, the evidences in the literature support that gut microbiota can influence CNS disorders like autism, depression, and schizophrenia.