The metabolic nature of inflammatory bowel diseases

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. Experimental and clinical evidence supports a role of metabolic perturbation in the development of gut inflammation in inflammatory bowel disease (IBD). This Review discusses the role of diet and metabolic inflammation in IBD, outlining key concepts and highlighting the links between metabolism and inflammation in IBD. Key points Experimental gut inflammation is driven by excessive intake of simple carbohydrates, polyunsaturated fatty acids and food additives in a Western diet. Innate immune receptors and the commensal microbiota modulate diet-induced metabolic inflammation in and beyond the gut. Epidemiological studies indicate that the westernization of diet conveys a risk of developing inflammatory bowel disease (IBD). Translational studies demonstrate perturbation of immunometabolism and host–microorganism commensalism in IBD. Conceptual nutritional trials corroborate the inflammatory nature of a Western diet in IBD, supporting the concept of diet-induced metabolic gut inflammation.