Features of the gut brain axis

Features of the gut brain axis

The brain and the gut are intimately connected via the gut–brain axis, which is a bidirectional communication system involving neural and humoral mechanisms. Neural connections involve the central, autonomic and enteric nervous systems. The enteric nervous system receives modulatory input from the brain and provides information to the brain via ascending neural circuits; it can also operate independently of the brain.

The effector limb of the enteric nervous system integrates physiological responses (including gut motility and secretion) and also modulates immune activity, as most immune cells possess receptors for neurotransmitters. The afferent limb comprises sensory nerves that contribute to gut reflexes and convey information to the brain. This information includes signals about noxious stimuli such as gut distension, as well as potentially dangerous signals, including the presence of bacterial endotoxins or pro-inflammatory cytokines. This information is conveyed to the brain and might result in pain, discomfort, or compensatory responses that are aimed at restoring homeostasis; these responses might involve changes in the gut physiology or immune function (for example, cytokine secretion).

The autonomic nervous system links the gut and the brain and consists of sympathetic and parasympathetic nerves. The vagus nerve is a major pathway for signals originating from the foregut and the proximal colon, whereas sacral parasympathetic nerves innervate the distal colon. The sympathetic system primarily exerts an inhibitory influence on the gut, decreasing intestinal motor function and secretion via the release of neurotransmitters such as noradrenaline. Responses to stress are conveyed via the sympathetic system and the hypothalamic–pituitary–adrenal axis.

The autonomic input from the gut is connected to the limbic system of the brain, the most important components of which are the hippocampus, the amygdala and the limbic cortex. The limbic system is responsible for a range of brain processes: the amygdala integrates responses to fear and arousal, whereas the hippocampus is responsible for memory and spatial navigation, and the limbic cortex regulates olfaction and integrates sensory and motor functions. The limbic system receives input from other brain regions that are responsible for a range of behaviours; these regions include the prefrontal cortex, the anterior cingulated gyrus, the temporal lobe and basal ganglia. Communication between the limbic and autonomic systems provides the neural circuitry underlying the strong link between behaviour and gut function in health (such as stomach 'butterflies') and disease (such as irritable bowel syndrome).

The humoral components of the gut–brain axis consist of the hypothalamic–pituitary–adrenal axis, the enteroendocrine system and the mucosal immune system. The hypothalamic–pituitary–adrenal axis is responsible for stress responses, resulting in the release of corticosterone, adrenaline and noradrenaline. Enteroendocrine cells produce hormones such as cholecystokinin and ghrelin, both of which regulate appetite, and 5-hydroxytryptamine, which has a broad range of effects on gut and brain functions.

Nature Reviews Microbiology 10, 735-742 (November 2012)