Gut microbiome-mediated regulation of neuroinflammation

Abstract

The intestinal microbiome influences neuroinflammatory disease in animal models, and recent studies have identified multiple pathways of communication between the gut and brain. Microbes are able to produce metabolites that enter circulation, can alter inflammatory tone in the intestines, periphery, and central nervous system (CNS), and affect trafficking of immune cells into the brain. Additionally, the vagus nerve that connects the enteric nervous system to the CNS is implicated in modulation of brain immune responses. As preclinical research findings and concepts are applied to humans, the potential impacts of the gut microbiome-brain axis on neuroinflammation represent exciting frontiers for further investigation.

Figure 1.. The gut microbiome influences neuroinflammatory disease through diverse pathways.

Microbes can affect distal systems, such as the central nervous system, through many routes, including microbe-derived molecules, immune activation, and direct signaling. Metabolites and other microbial-derived molecules alter microglial inflammatory tone, can act as molecular mimics of neural antigens, and can directly interact with host proteins to exacerbate neuropathology. Intestinal and systemic inflammation can affect risk for neuroinflammatory disease, and signals from microbes stimulate peripheral γδ T and Th17 cells to traffic to the brain. Direct connections exist between the gut and the brain via the vagus nerve, and stimulating or severing this connection impacts neuroinflammation, neurological symptoms, and brain pathology. The gut-immune-brain communication may be important to consider when developing therapeutics for certain human CNS disorders.