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  • Review Article
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Gut feelings: the emerging biology of gut–brain communication

Key Points

  • Recent neurobiological insights into this gut–brain crosstalk have revealed a complex, bidirectional communication system that not only assures proper maintenance of gastrointestinal homeostasis and digestion but is likely to have multiple effects on affect, motivation and higher cognitive functions.

  • Sympathetic and parasympathetic innervations modulate intestinal function and are likely to mediate the reported emotion-related patterns of regional changes in motor, secretory and possibly immune activity in the gastrointestinal tract.

  • There are three basic mechanisms by which sensory information is encoded in the gut: by primary afferent neurons, by immune cells and by enteroendocrine cells.

  • Both extrinsic and intrinsic primary afferents provide input to multiple reflex loops that are aimed at optimizing gut function and maintaining gastrointestinal homeostasis during internal perturbations.

  • The output of enteroendocrine cells is involved both in the regulation of digestive functions through enteric nervous system circuits, as well as in the regulation of CNS processes through endocrine and paracrine signalling to vagal afferents.

  • Immune cells in the gut remain immunologically hyporesponsive to commensal bacteria, while maintaining their responsiveness to pathogenic organisms, and their products indirectly influence the functional properties of enteroendocrine cells.

  • Recent evidence suggests that various forms of subliminal interoceptive inputs from the gut, including those generated by intestinal microbes, may influence memory formation, emotional arousal and affective behaviours. The human insula, and related brain networks (including the anterior cingulate cortex, orbitofrontal cortex and amygdala), has emerged as the most plausible brain region to support this integration.

  • It remains to be determined whether intuitive decision making is based on an interoceptive map of gut responses that enables the brain to make rapid gut-based decisions based on interoceptive memories of such responses.

  • There is extensive evidence of alterations in brain–gut signalling systems during perturbation to gut homeostasis, in several chronic gastrointestinal disorders and in eating disorders. Further understanding of the bidirectional crosstalk between the brain and the digestive system may aid the development of effective therapies for these conditions.

Abstract

The concept that the gut and the brain are closely connected, and that this interaction plays an important part not only in gastrointestinal function but also in certain feeling states and in intuitive decision making, is deeply rooted in our language. Recent neurobiological insights into this gut–brain crosstalk have revealed a complex, bidirectional communication system that not only ensures the proper maintenance of gastrointestinal homeostasis and digestion but is likely to have multiple effects on affect, motivation and higher cognitive functions, including intuitive decision making. Moreover, disturbances of this system have been implicated in a wide range of disorders, including functional and inflammatory gastrointestinal disorders, obesity and eating disorders.

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Figure 1: Gut to brain communication.
Figure 2: Gut–brain signalling related to food intake.
Figure 3: Gut signalling systems, gut sensations and meta-representations of such sensations.
Figure 4: Interoceptive memory and prediction error in chronic disease.

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Acknowledgements

Supported by grants DK048351, DK064539, DK082370 and AT002681 from the National Institutes of Health.

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Glossary

Enteric nervous system

Ganglionated plexus of neurons that is located between the layers of the gut. These neurons, which are equal in number to those in the spinal cord, are able to regulate basic gut functions, such as the peristaltic reflex.

Emotional motor system

System of parallel outflows from cortico–limbic–pontine networks that is engaged during distinct homeostatic states. A medial component provides tonic modulation of spinal reflexes and a lateral component plays a part in executing distinct regional motor patterns of the viscera through autonomic pathways

Enteroendocrine cell

Specialized epithelial cell that releases secretory granules, containing one or several gut peptides, on the basolateral side (and possibly luminal side) in response to luminal chemical, mechanical and possibly neural stimuli.

Enterochromaffin cell

Specialized epithelial cell that releases secretory granules, containing primarily serotonin, on the basolateral side (and possibly luminal side) in response to luminal chemical, mechanical and possibly neural stimuli.

Intrinsic reflex

Also known as an intramural reflex. A reflex of the enteric nervous system in which the afferents, interneuron and efferent neurons that are involved are all contained within the gut wall.

Intrinsic, primary afferent

Afferent neuron with its cell body contained within the enteric nervous system, that encodes mechanical and paracrine signals.

Commensal bacteria

Refers to the 100 trillion bacteria that live in symbiosis with the gut and make up the intestinal microflora.

Myenteric

Subplexus of the enteric nervous system, which is localized between the circular and longitudinal muscle layer.

Ego-syntonic

Psychological term referring to behaviours, values and feelings that are in harmony with, or acceptable to, the needs and goal of a person or that are consistent with a person's ideal self image. This trait is typically seen in patients with anorexia nervosa.

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Mayer, E. Gut feelings: the emerging biology of gut–brain communication. Nat Rev Neurosci 12, 453–466 (2011). https://doi.org/10.1038/nrn3071

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