Fig. 1

Proposed mechanisms and pathways of the microbiota-gut-brain axis: Gut microbes synthesize a vast array of neuroactive molecules including neurotransmitters such as GABA and through fermentation, short chain fatty acids, which have effects on the nervous system. The intestinal microbiota also has direct and indirect effects of on the intestinal epithelium, local mucosal immune system, enteric nervous system and spinal and vagal nerves. Mediators and signals from these systems, including cytokines and neurotransmitters, modulate central nervous system (CNS) function and neuroendocrine responses such as the hypothalamus pituitary adrenal axis (HPA). In turn signals from the CNS and neuroendocrine system, including cortisol, catecholamines and acetylcholine, can alter gut microbiota composition. While such bi-directional signaling has been identified, definitive evidence for the specific roles of these pathways in communication between gut microbes and the brain is largely lacking