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The Gut–Brain Axis
The gut–brain axis (GBA) it is a complex network in which the CNS and the enteric nervous system (ENS) interact with each other in a bilateral manner by several mechanisms, including nervous, hormonal, metabolic, and immunological ones. Recently, this relationship has been described as the ‘microbiota–gut–brain axis’ because of the known role of the gut microbiota in maintaining a physiological brain–gut relationship and its participation in the pathogenesis of several diseases. In this complex network, a plethora of interactions take place.
The brain—a central, coordinating element of the GBA—receives and releases information via the enteric, sympathetic, and autonomic nervous systems  Further, the hypothalamus–pituitary axis (HPA) as well as sympathetic and cortisol-related immune regulations are involved . The GBA is bidirectional; the CNS takes part in the modulation of ENS functions in several ways—directly and indirectly (directly through changes induced in the microenvironment of the gastrointestinal tract, and indirectly through signaling molecules)—both antagonistically and synergistically . Three major pathways of GBA communication can be distinguished—the vagus nerve pathway, the neuroendocrine pathway, and the immune-related pathway .
It has been proverbially said, that immunity derives from the intestine and this is not an unjustified statement, as the human gut contains the largest concentration of immune cells in the organism . The proper functioning of the intestines appears crucial in guarding autoimmunity, especially due to the fact that the intestines are capable of recognizing and distinguishing potentially harmful bacteria from commensal ones . The latter are involved in both adaptive and innate immunity. The microbiota, through microbe-associated molecular patterns (MAMPs), is involved in promoting the function of cells and cytokines affecting the CNS, which mainly include Il-6, Il-1a, IL-1b, and TNF-α .
A vast majority of the gastrointestinal tract functions are controlled by the autonomic nervous system and include bile secretion, motility of the gut, mucosal production, and even the immune response . Normally, in the case of the human body, each action triggers a response; therefore, the information entering the CNS through the autonomic nervous system (ANS) is subsequently transmitted to the organs of the body through closed positive and negative feedback loops . The HPA works mainly through the so-called stress hormones and is responsible for the rapid reactions of the body; therefore, disturbances in its functioning exert a significant impact on the entire organism. It seems that in both human and animal models, the HPA is overreactive when the gut microbiota is disturbed, and this overactivity may reversely result in disturbances of the gut microbiota . The mucosal barrier in the gastrointestinal tract is an extremely important element, constituting the organ’s border and connecting many systems in the human body. It consists of both building and functional elements, including a layer of mucus and phospholipids. Furthermore, the submucosal blood flow has a regulatory effect on the production and release of several mediators. The maintenance of mucosal barrier homeostasis depends on a plethora of bidirectional interacting elements, with a significant role played by the gut–brain axis. As Dolores Sgambato et. al. observed, among the mechanisms included in this cooperation we can find the aforementioned hypothalamus–pituitary–adrenocortical (HPA) system, GABAergic and glutamatergic neurotransmission, thyrotropin release hormone, physiologically active lipids, CGRP, melatonin, as well as peptides such as GLP-1, YY peptide, leptin, and ghrelin. The complexity of this physiology results in a similarly complex pathophysiology: any disturbance in this system can have a negative effect on the integrity of the mucosal barrier .
Several microbial molecules are similar to the human ones. Intestinal cells (e.g., enterocytes and secretory cells) are capable of producing and releasing cytokines, chemokines, and, most importantly, endocrine and neurotransmitter molecules ( e.g., PYY, GLP-1, 5-HT, GABA) . Furthermore, the microbiota is able to produce metabolites with neuromodulatory properties, with visible results in the ANS . Those metabolites include dopamine, 5-HT, GABA, short-chain fatty acids (SCFAs) capable of crossing the brain–blood barrier (BBB), thus influencing neurotransmission within the CNS . Interestingly, several different polymodal receptors are observed within the vagus nerve. The vagus nerve is responsible for gastrointestinal tract innervation and thus it is able not only to recognize physical stimuli like stretching but also to detect the previously mentioned bacteria-produced molecules . A study of the so-called ‘cholinergic anti-inflammatory pathway’ proved that the efferent part of the vagus nerve has protective abilities through the inhibition of proinflammatory cytokines . Interestingly, patients who undergo vagotomy because of ulcers appear to be more susceptible to neuropsychiatric diseases . On the other hand, stimulation of the vagus nerve in mice increased neurogenesis in the hippocampus .
2. Pathophysiology of Helicobacter pylori Infection
The entry is from 10.3390/cells10092191
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