Diet fuelling inflammatory bowel diseases: preclinical and clinical concepts

Abstract

The diet and gut microbiota have been extensively interrogated as a fuel for gut inflammation in inflammatory bowel diseases (IBDs) in the last few years. Here, we review how specific nutrients, typically enriched in a Western diet, instigate or deteriorate experimental gut inflammation in a genetically susceptible host and we discuss microbiota-dependent and independent mechanisms. We depict the study landscape of nutritional trials in paediatric and adult IBD and delineate common grounds for dietary advice. Conclusively, the diet reflects a critical rheostat of microbial dysbiosis and gut inflammation in IBD. Dietary restriction by exclusive enteral nutrition, with or without a specific exclusion diet, is effectively treating paediatric Crohn's disease, while adult IBD trials are less conclusive. Insights into molecular mechanisms of nutritional therapy will change the perception of IBD and will allow us to enter the era of precision nutrition. To achieve this, we discuss the need for carefully designed nutritional trials with scientific rigour comparable to medical trials, which also requires action from stake holders. Establishing evidence-based dietary therapy for IBD does not only hold promise to avoid long-term immunosuppression, but to provide a widely accessible therapy at low cost. Identification of dietary culprits disturbing gut health also bears the potential to prevent IBD and allows informed decision making in food politics.

Keywords: diet; dietary factors; gut inflammation; inflammatory bowel disease; intestinal microbiology.

Figure 1

The Western diet impairs epithelial immune responses and promotes dysbiosis and inflammation. A Western diet is enriched with simple carbohydrates, fat (eg, saturated and polyunsaturated fatty acids and cholesterol) and food additives (eg, emulsifiers, food colourants, processed carbohydrates). These compounds may directly induce compositional and functional alterations of the gut microbiota, which partly impairs epithelial functions in the gut, that is, perturbs Paneth cells and the gut barrier. Consequently, a dysbiotic microbiota promotes susceptibility to gut inflammation by perturbation of host–microbe interactions. Polyunsaturated fatty acids in a Western diet trigger acute enteritis in mice without evidence for gut microbial dysbiosis, which is rather controlled by epithelial endoplasmic reticulum homeostasis (maintained by X-box-binding protein 1 and Glutathione peroxidase 4). Cholesterol exposure induces an acute inflammatory response involving neutrophils in the gut of mice, possibly by inflammasome sensing. GPX4, Glutathione peroxidase 4; IL, interleukin; XBP1, X-box-binding protein 1.

Figure 2

The diet and gut microbiota perturb immune responses in IBD. Dietary constituents such as macronutrients and food additives have been shown to affect the gut microbiota in humans. Diet-induced alterations of the gut microbiota may exert diverse effects on gut mucosal immune responses and IBD-associated dysbiosis promotes gut inflammation in preclinical models, partly by loss of production of beneficial microbial metabolites, such as SCFAs and indole derivatives. In addition, the bloom of certain pathobionts may impair the epithelial barrier and stimulate a proinflammatory environment. AhR, arylhydrocarbon receptor; BA, bile acid; ER, endoplasmic reticulum; H2S, hydrogen sulfide; IBD, inflammatory bowel diseases; IL, interleukin; SCFA, short chain fatty acid.