The role of microbiome in central nervous system disorders

Abstract

Mammals live in a co-evolutionary association with the plethora of microorganisms that reside at a variety of tissue microenvironments. The microbiome represents the collective genomes of these co-existing microorganisms, which is shaped by host factors such as genetics and nutrients but in turn is able to influence host biology in health and disease. Niche-specific microbiome, prominently the gut microbiome, has the capacity to effect both local and distal sites within the host. The gut microbiome has played a crucial role in the bidirectional gut-brain axis that integrates the gut and central nervous system (CNS) activities, and thus the concept of microbiome-gut-brain axis is emerging. Studies are revealing how diverse forms of neuro-immune and neuro-psychiatric disorders are correlated with or modulated by variations of microbiome, microbiota-derived products and exogenous antibiotics and probiotics. The microbiome poises the peripheral immune homeostasis and predisposes host susceptibility to CNS autoimmune diseases such as multiple sclerosis. Neural, endocrine and metabolic mechanisms are also critical mediators of the microbiome-CNS signaling, which are more involved in neuro-psychiatric disorders such as autism, depression, anxiety, stress. Research on the role of microbiome in CNS disorders deepens our academic knowledge about host-microbiome commensalism in central regulation and in practicality, holds conceivable promise for developing novel prognostic and therapeutic avenues for CNS disorders.

Keywords: Central nervous system; Gut–brain axis; Microbiome; Neuro-immune disorders; Neuro-psychiatric disorders.

Figure 1. Microbiome-gut-brain axis in relation to CNS disorders

Multiple pathways guide the downward and upward directions of the microbiome-gut-brain axis in the contexts of health and disease. (A) Downwardly, CNS controls gut microbiome composition through satiation signaling peptides that affect nutrient availability, endocrines that affect gut functions and neural pathways. HPA axis release of cortisol regulates gut movement and integrity. Immune (cells, cytokines and sIgAs) pathways can be turned on in response to altered gut functions. Endocrine and neural pathways can also regulate the secretion from specialized gut epithelial cells, including paneth cells, enteroendocrine cells (ECC) and goblet cells. Their secretory products affect the survival and resident environment of microbiota. (B) Upwardly, gut microbiome controls CNS activities through neural (direct activation of neurons by microbiome), endocrine (e.g. ECC release of 5-HT), metabolic (microbiota synthesis of neuroactive molecules), and immune (CNS infiltrating immune cells and systemic inflammation) pathways. Microbiome influences CNS at healthy (neuro-development) and disease (a range of neuro-immune and neuro-psychiatric disorders) states. Gut luminal microbiota, their products sampled by APCs and epithelium-attaching SFBs mediate peripheral immune education. Gut microbiome composition, specific strains within microbiota, probiotic treatment, microbiota-derived products and other factors constitute the scope of microbiome studies.