Fig. 1.

Schematic for microbiota regulation of neuroinflammation and HPA axis activity. Communication within the microbiota-gut-brain axis involves the complex co-ordination of a number of factors and systems. The microbiota can govern events in the periphery and CNS by various means of communication including vagal nerve activation, cytokine production, neuropeptide and neurotransmitter release, SCFA release and microbial by-products, and by utilising the lymphatic and systemic circulation. Once these signals penetrate the blood brain barrier and reach the brain, they can influence the maturation and activation state of the microglia. Once activated, microglia play a key role in immune surveillance, synaptic pruning and clearance of debris. They also facilitate a number of everyday functions in the brain, including the regulation of HPA axis activation state. The release of glucocorticoids (cortisol) as a consequence of HPA axis activation can in turn regulate the activation state of brain microglia, as well as influence cytokine release and trafficking of monocytes from the periphery to the brain. HPA Hypothalamic-Pituitary-Adrenal; BDNF Brain derived neurotrophic factor; LTP Long term potentiation; BBB Blood-brain barrier; GC Glucocorticoids; GR Glucocorticoid receptor; FFAR Free fatty acid receptor; SCFA Short chain fatty acid; NP Neuropeptide; NT Neurotransmitter; DC Dendritic cell; EEC Enteroendocrine cell.