The Gut Brain Axis (GBA)
Gut bacteria use primarily GABA, DA, NE, 5-HT and histamine to communicate with the central nervous system (CNS) [3], but also intermediate compounds, notably short-chain fatty acids (SCFAs) [4], tryptophan [5], and secondary bile acids [6]. Signals generated by these neurotransmitters and molecules are transported to the brain via afferent vagus nerve (VN) fibers. In response, the brain sends signals back to enterochromaffin cells (ECCs) and enteroendocrine cells (EECs) in the gut wall, and the mucosal immune system via efferent VN fibers [7]. Activation of the VN improves the integrity of the gut wall, reduces peripheral inflammation, and inhibits the release of pro-inflammatory cytokines [8]. Signals generated by the hypothalamus reach the pituitary and adrenal glands and communicate with EECs via the hypothalamic pituitary adrenal axis (HPA) [9]. The intricate control of entero-endocrine signaling and immune-responses keeps the gut microbiome in a balanced state. If unbalanced, the gut enters a state of dysbiosis, characterized by a drastic increase in Enterobacteriaceae, especially Escherichia, Shigella, Proteus and Klebsiella, and an increase in enterotoxin levels [10]. If left untreated, major gastrointestinal disorders, such as diarrhoea, ulcerative colitis (UC), Crohn’s disease, and other inflammable bowel diseases (IBDs) may develop [11,12,13]. In severe cases, elevated toxin levels may alter the functioning of the intestinal– and blood–brain barrier (BBB) that may lead to neurodegeneration [10,14,15,16].
Neurotransmitters
Since gut microbiota co-evolved with humans and animals to perform neuronal functions, it is safe to assume that certain species, notably those that colonize the gastro-intestinal tract (GIT) first, play the largest role in the synthesis and degradation of neurotransmitters.