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Neural signalling of gut mechanosensation in ingestive and digestive processes

Nature Reviews Neuroscience volume 23, pages 135–156 (2022)Cite this article

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Abstract

Eating and drinking generate sequential mechanosensory signals along the digestive tract. These signals are communicated to the brain for the timely initiation and regulation of diverse ingestive and digestive processes — ranging from appetite control and tactile perception to gut motility, digestive fluid secretion and defecation — that are vital for the proper intake, breakdown and absorption of nutrients and water. Gut mechanosensation has been investigated for over a century as a common pillar of energy, fluid and gastrointestinal homeostasis, and recent discoveries of specific mechanoreceptors, contributing ion channels and the well-defined circuits underlying gut mechanosensation signalling and function have further expanded our understanding of ingestive and digestive processes at the molecular and cellular levels. In this Review, we discuss our current understanding of the generation of mechanosensory signals from the digestive periphery, the neural afferent pathways that relay these signals to the brain and the neural circuit mechanisms that control ingestive and digestive processes, focusing on the four major digestive tract parts: the oral and pharyngeal cavities, oesophagus, stomach and intestines. We also discuss the clinical implications of gut mechanosensation in ingestive and digestive disorders.

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Fig. 1: Mechanosensory signalling pathways from the digestive tract to the brain.
Fig. 2: Neural circuits for mechanosensory control of digestive processes in the oral cavity.
Fig. 3: Neural circuits for mechanosensory control of the digestive processes in the oesophagus, stomach and intestines.

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Acknowledgements

The authors thank D.-Y. Kim for help in the literature search, S.J. Moon for comments on the manuscript and members of the S.-Y.K. laboratory for critical discussions. This work was supported by Samsung Science and Technology Foundation under Project Number SSTF-BA2001-09.

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  1. Department of Chemistry, Institute of Molecular Biology and Genetics, Seoul National University, Seoul, South Korea

    Minyoo Kim, Gyuryang Heo & Sung-Yon Kim

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All authors researched data for the article. S.-Y.K. and M.K. contributed substantially to discussion of the content. The authors all wrote the article and reviewed and/or edited the manuscript before submission.

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Correspondence to Sung-Yon Kim.

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Glossary

Bolus

A ball-like mixture of chewed food and saliva that forms in the oral cavity.

Chyme

A thick semi-fluidic mass consisting of partially digested food, gastric acid and digestive enzymes produced by the mechanical and chemical breakdown of the bolus in the stomach.

Motilities

Contractions and relaxations of smooth muscles in the digestive tract that mix, triturate and propel ingesta, supporting numerous digestive functions including swallowing, peristalsis, gastric relaxation and emptying, and defecation.

Mechanoreceptor

A specialized sensory cell that responds to a mechanical stimulus, such as pressure or distortion. Examples include Merkel cells in the skin, mechanosensory vagal nerve endings in the stomach and enterochromaffin cells in the intestines.

Low-threshold mechanoreceptors

Mechanoreceptors that detect innocuous mechanical stimuli.

High-threshold mechanoreceptors

Mechanoreceptors that only respond to intense mechanical stimuli, such as pinching and strong stretching, and are regarded as a type of nociceptor.

Intraganglionic laminar endings

(IGLEs). A morphologically defined type of vagal or spinal sensory nerve endings that is characterized by highly branching, flattened lamellar processes, found in the myenteric ganglia of the oesophagus, stomach and intestines, considered to function as a tension receptor.

Intramuscular arrays

(IMAs). A major morphologically defined sensory terminal type that consists of varicose nerve fibres branching and extending parallel to muscle fibres within the longitudinal or circular muscle layers throughout the gastrointestinal tract; these are proposed, but not demonstrated, as stretch receptors.

Intraganglionic varicose endings

(IGVEs). A morphological type of spinal afferent endings consisting of branching varicose nerve fibres that is found in the myenteric plexus throughout the gastrointestinal tract.

Dogiel type I neurons

A morphologically defined type of enteric neurons with a relatively small cell body, short, flat and thick dendrites, and a single axon, corresponding to electrophysiologically classified S (synaptic)-neurons, as it receives prominent and fast excitatory synaptic inputs.

Dogiel type II neurons

A morphological type of enteric neurons with a large smooth cell body and multiple axons that project locally to the myenteric plexus and to the mucosa. These are often termed ‘after-hyperpolarizing’ neurons, as most exhibit slow and prolonged hyperpolarizing currents following an action potential.

Intestinofugal neurons

Intestinal enteric neurons that project to sympathetic neurons in the prevertebral ganglia (that is, celiac, superior mesenteric or inferior mesenteric ganglia).

Enterochromaffin cells

The largest population of enteroendocrine cells in the intestinal epithelium that release serotonin in response to various chemical, mechanical and neural stimuli, and synthesize 95% of the body’s serotonin.

Filiform papillae

The most numerous lingual papillae that cover most of the dorsal surface of the anterior two thirds of the tongue. Filiform papillae are devoid of taste buds and are considered to play a major role in lingual mechanosensation.

Lingual nerves

Branches of the mandibular division of the trigeminal sensory nerve that innervate the tongue. The chorda tympani nerve also joins the lingual nerve between the lateral and medial pterygoid muscles.

Chorda tympani

A branch of the facial nerve that innervates the anterior two thirds of the tongue and submandibular ganglion.

Sensory trigeminal nerve nuclei

The brainstem nuclei to which trigeminal sensory fibres primarily project, consisting of the mesencephalic nucleus (Me5), principal sensory nucleus (Pr5) and spinal trigeminal nucleus (Sp5).

Vagovagal reflex

A digestive tract reflex coordinated by vagal afferents and efferents, including secondary peristalsis, oesophageal distension-induced sphincter relaxation, receptive relaxation of the stomach and adaptive relaxation of the stomach.

Gag reflex

A protective response in which the back of the throat contracts to prevent swallowing of harmful substances.

Flavour

A multisensory perception of food consisting of both chemical (for example, smell and taste) and physical (for example, texture and temperature) sensations.

Dysphagia

Difficulty in swallowing.

Achalasia

Failure of oesophageal smooth muscle relaxation, which hinders the passage of ingesta, causing dysphagia, regurgitation and, occasionally, chest pain.

Faecal incontinence

Inability to control bowel movement resulting in unexpected stool leakage.

Irritable bowel syndrome

(IBS). A functional gastrointestinal disorder characterized by a group of symptoms including abdominal discomfort or pain, bloating sensation and stool irregularities.

Roux-en-Y gastric bypass

The most commonly performed bariatric surgery involving partitioning off the proximal stomach to create a small pouch and connecting the pouch directly to the jejunum.

Adjustable gastric banding

A type of bariatric surgery procedure in which an adjustable band is placed around the proximal stomach to create a small gastric pouch.

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Kim, M., Heo, G. & Kim, SY. Neural signalling of gut mechanosensation in ingestive and digestive processes. Nat Rev Neurosci 23, 135–156 (2022). https://doi.org/10.1038/s41583-021-00544-7

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