The gut-brain axis: interactions between enteric microbiota, central and enteric nervous systems

Abstract

The gut-brain axis (GBA) consists of bidirectional communication between the central and the enteric nervous system, linking emotional and cognitive centers of the brain with peripheral intestinal functions. Recent advances in research have described the importance of gut microbiota in influencing these interactions. This interaction between microbiota and GBA appears to be bidirectional, namely through signaling from gut-microbiota to brain and from brain to gut-microbiota by means of neural, endocrine, immune, and humoral links. In this review we summarize the available evidence supporting the existence of these interactions, as well as the possible pathophysiological mechanisms involved. Most of the data have been acquired using technical strategies consisting in germ-free animal models, probiotics, antibiotics, and infection studies. In clinical practice, evidence of microbiota-GBA interactions comes from the association of dysbiosis with central nervous disorders (i.e. autism, anxiety-depressive behaviors) and functional gastrointestinal disorders. In particular, irritable bowel syndrome can be considered an example of the disruption of these complex relationships, and a better understanding of these alterations might provide new targeted therapies.

Keywords: Gut-brain axis; central nervous system; enteric microbiota; enteric nervous system; irritable bowel syndrome.

Figure 1

Microbiome gut-brain axis structure The central nervous system and in particular hypothalamic pituitary adrenal (HPA) axis (in dashed line) can be activated in response to environmental factors, such as emotion or stress. HPA is finalized to cortisol release and is driven by a complex interaction between amygdala (AMG), hippocampus (HIPP), and hypothalamus (HYP), constituting the limbic system. HYP secretion of the corticotropin-releasing factor (CRF) stimulates adrenocorticotropic hormone (ACTH) secretion from pituitary gland that, in turn, leads to cortisol release from the adrenal glands. In parallel, central nervous system communicate along both afferent and efferent autonomic pathways (SNA) with different intestinal targets such as enteric nervous system (ENS), muscle layers and gut mucosa, modulating motility, immunity, permeability and secretion of mucus. The enteric microbiota has a bidirectional communication with these intestinal targets, modulating gastrointestinal functions and being itself modulated by brain-gut interactions