Brain-Gut Axis: Clinical Implications

Abstract

This article provides an overarching view of what is currently known about the physiology of the brain-gut axis in both health and disease and how these concepts apply to irritable bowel syndrome, the most common functional gastrointestinal disorder in pediatrics.

Keywords: Brain–gut axis; Brain–gut–microbiome axis; Enteric nervous system; Irritable bowel syndrome; Serotonin.

Copyright © 2018 Elsevier Inc. All rights reserved.

Figures

Fig. 1.

Communication between the enteric nervous system (ENS) and central nervous system (CNS, brain and spinal cord) is bidirectional and continuous. The gut and the brain communicate via the parasympathetic nervous system through afferent sensory pathways of the vagus nerve and via the sympathetic nervous system through efferent motor pathways of the prevertebral ganglia. The brain–gut axis is also modulated by the enteric microbiota. The microbiota can modulate the CNS directly via the vagus nerve and/or indirectly by influencing the ENS and by production of metabolites that cross the blood brain barrier. Serotonin (5-HT) is important for brain–gut communication as both a neurotransmitter in the ENS and CNS, as well as a hormone present throughout the circulation. 5-HT is synthesized by tryptophan hydroxylase 1 (TPH1) in enterochromaffin (EC) cells, TPH2 in neurons, and is inactivated after reuptake primarily by the serotonin reuptake transporter (SERT). 5-HIAA, 5-hydroxyindoleacetic acid; 5-HT, 5-hydroxytryptamine; MAO, monoamine oxidase; TPH, tryptophan hydroxylase; Trp, tryptophan.

Fig. 2.

The hypothalamic–pituitary–adrenal (HPA) axis influences the brain–gut axis. Stress can elicit an emotional response and hypothalamic activation. Activation of the hypothalamus induces the secretion of corticotropin-releasing factor (CRF). CRF activates the pituitary gland, and in response, adrenocorticotropic hormone is secreted. Adrenocorticotropic hormone (ACTH) acts on the adrenal gland to induce the secretion of cortisol. The increase in cortisol, a key hormone in stress response, acts on the gut to alter GI tract function, autonomic tone, visceral perception, and behavior, which all relate to irritable bowel syndrome (IBS).