Gut microbiome and autoimmune disorders

Abstract

Autoimmune diseases have long been known to share a common pathogenesis involving a dysregulated immune system with a failure to recognize self from non-self-antigens. This immune dysregulation is now increasingly understood to be induced by environmental triggers in genetically predisposed individuals. Although several external environmental triggers have been defined in different autoimmune diseases, much attention is being paid to the role of the internal micro-environment occupied by the microbiome, which was once termed "the forgotten organ." In this regard, the gut microbiome, serving as an intermediary between some of those external environmental effectors and the immune system, helps programming of the immune system to be tolerant to innocent external and self-antigens. However, in the presence of perturbed gut microbiota (dysbiosis), the immune system could be erroneously directed in favor of pro-inflammatory pathways to instigate different autoimmune processes. An accumulating body of evidence, including both experimental and human studies (observational and interventional), points to the role of the gut microbiome in different autoimmune diseases. Such evidence could provide a rationale for gut microbiome manipulation with therapeutic and even preventative intent in patients with established or predisposed to autoimmune diseases, respectively. Perturbations of the gut microbiome have been delineated in some immune mediated diseases, IBD in particular. However, such patterns of disturbance (microbiome signatures) and related pathogenetic roles of the gut microbiome are context dependent and cannot be generalized in the same exact way to other autoimmune disorders, and the contribution of the gut microbiome to different disease phenotypes has to be precisely defined. In this review, we revise the evidence for a role of the gut microbiome in various autoimmune diseases and possible mechanisms mediating such a role.

Keywords: Gut microbiome; auto-immune diseases; dysbiosis; immune dysregulation.

Graphical Abstract

Figure 1:

gut microbiome and autoimmune diseases (potential mechanisms). Perturbed gut microbiota can contribute to the development of autoimmune diseases through several proposed , including translocation of pathobionts and their proinflammatory products as lipopolysaccharides (LPS), molecular mimicry, which entails similarity between bacterial antigens and self-antigens in genetically predisposed individuals, and disordered metabolome (which normally helps contain inflammatory pathways in healthy state). Normally, different microbiota metabolites (SCFA in particular) can induce expansion of the immunoregulatory T-helper cells (T-Reg), innate lymphoid cells (ILC-3) and their immunoregulatory cytokines (IL-10, 22) while blocking proinflammatory pathways mediated by Th-17. Patients with autoimmune diseases (AID) usually exhibit gut epithelial barrier dysfunction with increased permeability facilitating bacterial translocation.