Modulatory Effects of Gut Microbiota on the Central Nervous System: How Gut Could Play a Role in Neuropsychiatric Health and Diseases

Abstract

Gut microbiome is an integral part of the Gut-Brain axis. It is becoming increasingly recognized that the presence of a healthy and diverse gut microbiota is important to normal cognitive and emotional processing. It was known that altered emotional state and chronic stress can change the composition of gut microbiome, but it is becoming more evident that interaction between gut microbiome and central nervous system is bidirectional. Alteration in the composition of the gut microbiome can potentially lead to increased intestinal permeability and impair the function of the intestinal barrier. Subsequently, neuro-active compounds and metabolites can gain access to the areas within the central nervous system that regulate cognition and emotional responses. Deregulated inflammatory response, promoted by harmful microbiota, can activate the vagal system and impact neuropsychological functions. Some bacteria can produce peptides or short chain fatty acids that can affect gene expression and inflammation within the central nervous system. In this review, we summarize the evidence supporting the role of gut microbiota in modulating neuropsychological functions of the central nervous system and exploring the potential underlying mechanisms.

Keywords: Anxiety; Brain-Gut axis; Depression; Gut microbiota; Stress.

Figure

Bidirectional interactions between gut microbiota, gut permeability and central nervous system (CNS). Increased gut permeability can lead to translocation of gut microbiota or metabolic products such as lipopolysaccharides through the intestinal barrier. Exposure of epithelial cells or mucosal immune cells to bacterial or metabolic products can lead to activation of an immune response and release of pro-inflammatory cytokines. Additionally, metabolic products can directly affect the function of enteric neurons, spinal sensory neurons and vagus nerve through activation to Toll-like receptors or translocation and release of neuroactive peptides and hormones. On the other hand, stress can lead to activation of the hypothalamus-pituitary axis and excessive release of the corticotropin-releasing factor. This hormone along with altered vagal activity can modulate the local activation of mast cells in the intestinal wall and release of cytokines, causing increased gut permeability. ENS, enteric nervous system.