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Intestinal plasticity and metabolism as regulators of organismal energy homeostasis

Nature Metabolism volume 4, pages 1444–1458 (2022)Cite this article

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Abstract

The small intestine displays marked anatomical and functional plasticity that includes adaptive alterations in adult gut morphology, enteroendocrine cell profile and their hormone secretion, as well as nutrient utilization and storage. In this Perspective, we examine how shifts in dietary and environmental conditions bring about changes in gut size, and describe how the intestine adapts to changes in internal state, bowel resection and gastric bypass surgery. We highlight the critical importance of these intestinal remodelling processes in maintaining energy balance of the organism, and in protecting the metabolism of other organs. The intestinal resizing is supported by changes in the microbiota composition, and by activation of carbohydrate and fatty acid metabolism, which govern the intestinal stem cell proliferation, intestinal cell fate, as well as survivability of differentiated epithelial cells. The discovery that intestinal remodelling is part of the normal physiological adaptation to various triggers, and the potential for harnessing the reversible gut plasticity, in our view, holds extraordinary promise for developing therapeutic approaches against metabolic and inflammatory diseases.

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Fig. 1: Basic anatomy of small intestine and colon.
Fig. 2: Dietary and microbial cues model the intestinal absorptive surface.
Fig. 3: Interplay of metabolites controls the balance between intestinal cell division, differentiation and growth.
Fig. 4: Nutrient uptake in the intestine is modified by circuitry of enteroendocrine cells, enterocytes and peripheral organs.

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Acknowledgements

This work received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme, ERC advanced grant (787470, IntraGutSex), Biotechnology and Biological Sciences Research Council (BB000528/1), and MRC intramural funding to I.M.-A.; and from an ERC consolidator grant (815962, Healthybiota), the Swiss National Science Foundation (grant 310030_205042) and the Clayton Foundation for Biomedical Research to M.T.

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  1. Ozren Stojanović

    Present address: Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK

Authors and Affiliations

  1. Department of Cell Physiology and Metabolism, Centre Medical Universitaire (CMU), Faculty of Medicine, University of Geneva, Geneva, Switzerland

    Ozren Stojanović & Mirko Trajkovski

  2. Diabetes Centre, Faculty of Medicine, University of Geneva, Geneva, Switzerland

    Ozren Stojanović & Mirko Trajkovski

  3. MRC London Institute of Medical Sciences, London, UK

    Irene Miguel-Aliaga

  4. Institute of Clinical Sciences, Faculty of Medicine, Imperial College London, London, UK

    Irene Miguel-Aliaga

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All authors conceptualized, discussed and wrote the paper. O.S. prepared the figures. M.T. initiated the project.

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Stojanović, O., Miguel-Aliaga, I. & Trajkovski, M. Intestinal plasticity and metabolism as regulators of organismal energy homeostasis. Nat Metab 4, 1444–1458 (2022). https://doi.org/10.1038/s42255-022-00679-6

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