## 2 Microbiota-Gut-Brain Axis  
### Concepts and Brief Mechanism of Microbiota-Gut-Brain Axis  
The microbiota, the intestine and the brain communicate through the microbiota-gut-brain axis and a disturbance of this axis is involved in the pathophysiology of neurodegenerative disorders [19]. A disturbance of this axis is also involved in the pathophysiology of several diseases, such as obesity and diabetes [19]. The gut microbiota talks to the brain by producing bioactive short-chain fatty acids (SCFAs) that can be absorbed and therefore enter the circulation and they are fairly short-lived detected at relatively low concentrations [20]. There is not a lot of evidence to suggest that at physiologically relevant levels that they enter the brain [21]. They have another mechanism when they can bind G-protein-coupled receptors such as free fatty acid receptors 2 and 3 (FFAR2/3) and importantly cells of the immune system express these receptors [22]. The immune system is talking to the brain and there are involved both humoral and neural pathways and there is the same possibility in the gut-brain axis where the humoral pathway it is probably not the SCFA directly accessing the brain but rather inducing hormonal changes in the periphery regulating immune function [23]. The visceral sensory pathway is important to the nucleus tract solitaire. In this area, neurons project to the limbic system including areas such as the amygdala which is involved in the regulation of emotional behavior all of which are affected by the gut microbiota. The pathways of communication are starting to be illuminated which creates even better opportunities for manipulating this pathway to improve health [24]. It is well known that the gut talks to the brain, but this dialogue is bi-directional. Therefore, it is not just the microbes or the immune system in the gut talking to the brain but it is also the brain talking back to the immune system or to the gut. Therefore, there is this two-way communication that goes back and forth regulatory feedback that leads to health or to dysbiosis of the gut, damage of the brain, and the whole body [25]. For example, gut metabolites can cross the intestine barrier or be recognized by receptors on the barrier to induce satiety. In the opposite direction, hormones produced by the host can affect the gut microbiota and gut health. Noradrenaline released by the adrenergic nerve can interact with certain Gram-negative bacteria in the gut and cause them to grow or be more virulent. Indeed, chronic stress which increases norepinephrine can cause dysbiosis and gut disease [26]. Therefore, diet has a big effect on our gut microbiota and its function. It is bi-directional communication between our brain and the gastro-intestinal (GI) system and it has been used to explain the intestinal function and even the perturbation whether acute or chronic. The components of the gut-brain axis is represented in Figure 1: the first is the gut-brain communication and that is known that there are two components to this the intrinsic and the extrinsic pathways [27]. There is an enteral nervous system,the myenteric plexus and the submucosal plexus which have a very intricate array of communication and use various receptors: the mechanoreceptors, the thermal receptor, the chemoreceptors and osmoreceptors. The sensory neurons sense, the particular stimulus and then pass it through the interneurons, to the motor neurons which can help in different functions such as the secretion, maintenance of the motility and absorptive functions of the gastrointestinal tract. It is important to understand that the enteral nervous system can function even in the absence of the CNS [28]. The VN is still the part of the colon and then it is a pelvic nerve that communicates through the nodose ganglion and then communicates to the CNS [29]. The second one is the spinal pathway through various nerves from T5 to L5 which eventually land up through the paravertebral ganglia into the spinal cord and then communicate to the CNS.