Abstract
Crohn’s disease and ulcerative colitis, phenotypically comprising a spectrum of inflammatory bowel diseases (IBDs), spread globally during the westernization of lifestyle and dietary habits over the past few decades. Here, we review experimental and clinical evidence for the metabolic nature of gut inflammation in IBD and delineate distinct parallels to the inflammatory state in metabolic diseases. Experimental evidence indicates that excessive intake of specific macronutrients in a Western diet fuels an inflammatory response in the gut by exploiting sensors of innate immunity and perturbation of gut microbial metabolism. Genetic IBD risk partly affects metabolism and stress signalling of innate immunity, and immunometabolism controls susceptibility to gut inflammation. Epidemiological and clinical studies indicate that specific nutrients in the Western diet pose a risk for the development of IBD and a poor disease course. Translational studies in IBD indicate perturbation of energy metabolism in immune cells and perturbation of gut microbial metabolism, which can be shaped by diet. In turn, dietary restriction by exclusive enteral nutrition induces remission in patients with IBD. Collectively, these studies support a metabolic underpinning of gut inflammation in IBD as described for metabolic inflammation in obesity and related disorders.
Key points
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Experimental gut inflammation is driven by excessive intake of simple carbohydrates, polyunsaturated fatty acids and food additives in a Western diet.
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Innate immune receptors and the commensal microbiota modulate diet-induced metabolic inflammation in and beyond the gut.
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Epidemiological studies indicate that the westernization of diet conveys a risk of developing inflammatory bowel disease (IBD).
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Translational studies demonstrate perturbation of immunometabolism and host–microorganism commensalism in IBD.
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Conceptual nutritional trials corroborate the inflammatory nature of a Western diet in IBD, supporting the concept of diet-induced metabolic gut inflammation.
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Acknowledgements
T.E.A. is supported by the Austrian Science Fund (FWF P33070) and the European Research Council (ERC–STG: 101039320). L.M. and J.S. are grateful for the support from the Austrian Society of Gastroenterology & Hepatology (ÖGGH). F.G. appreciates support from the Tyrolean Science Funds (TWF). H.T. received funding by the excellence initiative (Competence Centers for Excellent Technologies - COMET) of the Austrian Research Promotion Agency FFG: Research Center of Excellence in Vascular Ageing Tyrol, VASCage (K-Project Nr. 843536) funded by the BMVIT, BMWFW, the Wirtschaftsagentur Wien and the Standortagentur Tirol.
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All authors wrote and reviewed/edited the manuscript before submission. T.E.A., M.M., J.S., L.M., F.G. and H.T. made substantial contributions to the discussion of content. T.E.A., M.M., J.S., L.M. and F.G. researched data for the article. J.S., L.M. and F.G. prepared the figures and boxes.
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Nature Reviews Gastroenterology & Hepatology thanks Taku Kobayashi, who co-reviewed with Shintaro Sagami; Benoit Chassaing; and Dirk Haller for their contribution to the peer review of this work.
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Glossary
- Fibre
-
Term for complex carbohydrates mainly contained in plant-derived food.
- Metabolic inflammation
-
Chronic low-grade inflammation detectable in the serum of patients with metabolic diseases, such as obesity and type 2 diabetes, which stems from metabolically active tissues.
- Western diet
-
Dietary habit established in industrialized countries that is frequently characterized by an increased intake of simple carbohydrates, long-chain fatty acids and food additives as well as reduced intake of plant-derived fibre.
- Metabolic syndrome
-
A clinical phenotype characterized by obesity, elevated blood pressure, blood glucose and/or blood triglyceride concentration that is associated with a higher risk of cardiovascular diseases and type 2 diabetes.
- Immunometabolism
-
A concept in which diet-derived or host-derived metabolites regulate immune function and, vice versa, the immune system controls metabolism.
- Colitis
-
Inflammation affecting the large intestine.
- Enteritis
-
Inflammation affecting the small intestine.
- Exposome
-
A measure of an individual’s exposure to non-genetic (endogenous and exogenous) cues that affect health during a lifetime.
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Adolph, T.E., Meyer, M., Schwärzler, J. et al. The metabolic nature of inflammatory bowel diseases. Nat Rev Gastroenterol Hepatol 19, 753–767 (2022). https://doi.org/10.1038/s41575-022-00658-y
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DOI: https://doi.org/10.1038/s41575-022-00658-y
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