Background: The gut-brain axis plays a potential role in numerous
physiological and pathological conditions. Several substances link stomach with central
nervous system. In particular, hypothalamo-pituitary-adrenocortical axis, thyrotropinreleasing
factor-containing nerve fibers and capsaicin-sensitive nerves are principal
mediators of the harmful and protective central nervous system-mediated effects on
gastric mucosa. Also, existing evidence indicates that nitric oxide, prostaglandins and
calcitonin gene-related peptide play a role as final effectors of gastric protection.
Methods: We undertook a structured search of bibliographic databases for peerreviewed
research literature with the aim of focusing on the role of gut-brain axis in
gastric damage and protection. In particular, we examined manuscripts dealing with
the role of steroids, thyrotropin-releasing hormone, prostaglandins, melatonin, hydrogen sulfide and
peptides influencing food intake (i.e. leptin, cholecystokinin, peptide YY, central glucagon–like peptide-1,
and ghrelin). Also, the role of GABAergic and glutamatergic pathways in gastric mucosal protection have
Results: We found and reviewed 61 peer-reviewed papers dealing with the major aspects related to the
role of gut brain axis in gastric mucosal damage and protection.
Conclusions: A dense neuronal network links stomach with central nervous system and a number of
neurotransmitters and peptides functionally and anatomically related to central nervous system play a
major role in contributing to gastric mucosal integrity.
Exploiting the mechanisms underlying the connection between brain and gut may lead to a better
understanding of the pathophysiology of gastric mucosal injury and to an improvement in the prevention
and, eventually, management of gastric damage.