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  • Review Article
  • Published:

Gut feelings: mechanosensing in the gastrointestinal tract

Nature Reviews Gastroenterology & Hepatology volume 19, pages 283–296 (2022)Cite this article

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Abstract

The primary function of the gut is to procure nutrients. Synchronized mechanical activities underlie nearly all its endeavours. Coordination of mechanical activities depends on sensing of the mechanical forces, in a process called mechanosensation. The gut has a range of mechanosensory cells. They function either as specialized mechanoreceptors, which convert mechanical stimuli into coordinated physiological responses at the organ level, or as non-specialized mechanosensory cells that adjust their function based on the mechanical state of their environment. All major cell types in the gastrointestinal tract contain subpopulations that act as specialized mechanoreceptors: epithelia, smooth muscle, neurons, immune cells, and others. These cells are tuned to the physical properties of the surrounding tissue, so they can discriminate mechanical stimuli from the baseline mechanical state. The importance of gastrointestinal mechanosensation has long been recognized, but the latest discoveries of molecular identities of mechanosensors and technical advances that resolve the relevant circuitry have poised the field to make important intellectual leaps. This Review describes the mechanical factors relevant for normal function, as well as the molecules, cells and circuits involved in gastrointestinal mechanosensing. It concludes by outlining important unanswered questions in gastrointestinal mechanosensing.

Key points

  • Mechanosensation is the ability to sense mechanical forces and transduce them into physiological responses.

  • The gut is a mechanically active organ in which all cells must sense the forces emanating from the digestion of intraluminal contents and organ activity, such as motility.

  • All cells reside in tissue at a baseline mechanical state; the gastrointestinal tract is a layered (composite) organ in which the baseline mechanical state varies by spatial localization.

  • Non-specialized mechanosensory cells sense force to adjust their function; specialized mechanoreceptors are mechanosensory cells that guide physiological organ responses to mechanical stimuli.

  • Gastrointestinal mechanoreceptors share similarities with mechanoreceptors in other sensory and non-sensory organs; leveraging these similarities helps in understanding the purpose and function of mechanoreceptors in the gastrointestinal tract.

  • Mechanosensory circuits built into the gastrointestinal wall allow for spatial and temporal integration of mechanical stimuli into a coordinated physiological response (for example, peristaltic reflex), and connections to the extrinsic mechanosensory circuits are crucial for brain–gut communication (for example, sense of fullness).

  • Areas with research potential include the discovery of unknown mechanosensors, quantification of the baseline mechanical state of the gastrointestinal wall, and the development of novel tests for gut-specific mechanosensation.

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Fig. 1: Static mechanical properties of the gut wall.
Fig. 2: Dynamic activities of the gut wall.
Fig. 3: Circuits, cells and molecules involved in gut mechanosensation.

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Acknowledgements

The authors thank the members of the Mayo Clinic Enteric NeuroScience Program (ENSP) group (G. Farrugia, J. H. Szurszewski, S. J. Gibbons and D. R. Linden), P. Gottlieb (SUNY, Buffalo, NJ, USA) for their constructive feedback, and L. Busby for administrative assistance. NIH support is acknowledged for GM065841, DK128913 (A.M.-P.), and DK052766, DK106456, DK100223 (A.B.).

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Authors and Affiliations

  1. Enteric NeuroScience Program (ENSP), Division of Gastroenterology & Hepatology, Mayo Clinic, Rochester, MN, USA

    Arnaldo Mercado-Perez & Arthur Beyder

  2. Medical Scientist Training Program (MSTP), Mayo Clinic, Rochester, MN, USA

    Arnaldo Mercado-Perez

  3. Department of Physiology & Biomedical Engineering, Mayo Clinic, Rochester, MN, USA

    Arthur Beyder

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Glossary

Mechanosensors

Proteins directly involved in converting a mechanical stimulus into an intracellular electrochemical signal, for example, mechanogated ion channels that convert mechanical forces into an ionic flow.

Signal amplification

Intracellular signalling steps between the primary signal generated by the mechanosensor and the final cellular output.

Mechanotransducers

Proteins that amplify the signals generated by the mechanosensors and conduct the downstream cellular signalling in response to force.

Non-specialized mechanosensory cells

Cells with a given non-mechanosensory primary function that use mechanosensors to sense mechanical stimuli and tune their own function in response to the physical state of their environment.

Specialized mechanoreceptors

Cells whose primary function is the conversion of a mechanical stimulus into a physiological signal that influences the behaviour of other cells.

Receptor current

Ionic current generated during sensory transduction, such as the opening of the mechanogated ion channels.

Generator potentials

Transmembrane electrical potentials or voltage shifts due to receptor current that engage voltage-sensing transducer amplification elements.

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Mercado-Perez, A., Beyder, A. Gut feelings: mechanosensing in the gastrointestinal tract. Nat Rev Gastroenterol Hepatol 19, 283–296 (2022). https://doi.org/10.1038/s41575-021-00561-y

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