Impacts of microbiome metabolites on immune regulation and autoimmunity

Abstract

Summary A vast number of studies have demonstrated a remarkable role for the gut microbiota and their metabolites in the pathogenesis of inflammatory diseases, including multiple sclerosis (MS). Recent studies in experimental autoimmune encephalomyelitis, an animal model of MS, have revealed that modifying certain intestinal bacterial populations may influence immune cell priming in the periphery, resulting in dysregulation of immune responses and neuroinflammatory processes in the central nervous system (CNS). Conversely, some commensal bacteria and their antigenic products can protect against inflammation within the CNS. Specific components of the gut microbiome have been implicated in the production of pro‐inflammatory cytokines and subsequent generation of Th17 cells. Similarly, commensal bacteria and their metabolites can also promote the generation of regulatory T‐cells (Treg), contributing to immune suppression. Short‐chain fatty acids may induce Treg either by G‐protein‐coupled receptors or inhibition of histone deacetylases. Tryptophan metabolites may suppress inflammatory responses by acting on the aryl hydrocarbon receptor in T‐cells or astrocytes. Interestingly, secretion of these metabolites can be impaired by excess consumption of dietary components, such as long‐chain fatty acids or salt, indicating that the diet represents an environmental factor affecting the complex crosstalk between the gut microbiota and the immune system. This review discusses new aspects of host–microbiota interaction and the immune system with a special focus on MS as a prototype T‐cell‐mediated autoimmune disease of the CNS.

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