Figure 1.

The bidirectional nature of the gut/brain axis, and the potential of the gut microbiome as a therapeutic route. (A) Proposed model of the gut microbiota as an amplifier of immune/inflammatory response. The exact genetic and environmental impacts on gut microbial composition is yet to be fully understood. Furthermore, the cellular and or soluble mechanisms of the reciprocal interactions between the microbiome and the host are still needed to be elucidated. Recent findings show significant alterations in microbial taxa of the gut microbiome and potential associations with pro-inflammatory pathways that can lead to or amplify disease. An effective therapeutic intervention targeting the microbiota might have to counteract dysbiosis, leaky gut that promotes microbial translocation and subsequent inflammation, thus modulating disease pathology. (B) Animal models suggest that autoimmune diseases including MS could be associated with gut dysbiosis, increased intestinal permeability, microbial translocation, and local and systemic inflammation. Inflammatory mediators, such as TNF-α, are known to reduce the expression of tight junction proteins thereby increasing the intestinal barrier permeability. (C) Experimental evidence obtained in animal models also suggest that interventions shifting the immune responses towards immunoregulatory pathways based on regulatory cells producing anti-inflammatory cytokines such as IL-10, TGF-β or IL-35 can restore immune homeostasis and protect against CNS inflammatory demyelination. Reduced inflammatory mediators as well as the direct production of metabolites such as SCFA by the balanced microbiome would facilitate increasing the compromised epithelial integrity. CSFA: short-chain fatty acids; CNS: central nervous system; MS: multiple sclerosis; EAE: experimental autoimmune encephalomyelitis; CD: cluster of differentiation; Th: T helper; IL: interleukin; TNF: tumor necrosis factor; TGF: transforming growth factor.