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The gut as a sensory organ

Key Points

  • The lining of the digestive tract is exposed to an extraordinarily broad range of chemicals and organisms

  • The gut continuously monitors the composition of its contents to optimize digestion and absorption, and to ward off threats to its integrity

  • The gut has numerous sensors that detect nutrients, distension, symbiotic and pathogenic microorganisms, toxins and other components of its luminal contents

  • For the digestive system to react appropriately to its environment, the sensory information is communicated to extensive endocrine, neural, immune and nonimmune tissue defence systems

  • More than 20 receptors that face the luminal contents are potential therapeutic targets for diabetes, obesity and digestive disorders; restricting orally active therapeutics to the lumen could reduce off-target actions

Abstract

The gastrointestinal tract presents the largest and most vulnerable surface to the outside world. Simultaneously, it must be accessible and permeable to nutrients and must defend against pathogens and potentially injurious chemicals. Integrated responses to these challenges require the gut to sense its environment, which it does through a range of detection systems for specific chemical entities, pathogenic organisms and their products (including toxins), as well as physicochemical properties of its contents. Sensory information is then communicated to four major effector systems: the enteroendocrine hormonal signalling system; the innervation of the gut, both intrinsic and extrinsic; the gut immune system; and the local tissue defence system. Extensive endocrine–neuro–immune–organ-defence interactions are demonstrable, but under-investigated. A major challenge is to develop a comprehensive understanding of the integrated responses of the gut to the sensory information it receives. A major therapeutic opportunity exists to develop agents that target the receptors facing the gut lumen.

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Figure 1: Summary of sensory inputs to the gut and the effector systems that they influence.
Figure 2: Sensory systems at the luminal interface.
Figure 3: Multiple sensors and multiple downstream effectors of gut sensory systems, using the L cell as an example.

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Acknowledgements

Work from the University of Melbourne laboratory is supported by the National Health and Medical Research Council of Australia. We are grateful for insightful comments of J. Brock, H. Cox, J. Keast, A. Lomax and R. Young.

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Correspondence to John B. Furness.

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Furness, J., Rivera, L., Cho, HJ. et al. The gut as a sensory organ. Nat Rev Gastroenterol Hepatol 10, 729–740 (2013). https://doi.org/10.1038/nrgastro.2013.180

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