The role of diet in the aetiopathogenesis of inflammatory bowel disease

Abstract

Crohn's disease and ulcerative colitis, collectively known as IBD, are chronic inflammatory disorders of the gastrointestinal tract. Although the aetiopathogenesis of IBD is largely unknown, it is widely thought that diet has a crucial role in the development and progression of IBD. Indeed, epidemiological and genetic association studies have identified a number of promising dietary and genetic risk factors for IBD. These preliminary studies have led to major interest in investigating the complex interaction between diet, host genetics, the gut microbiota and immune function in the pathogenesis of IBD. In this Review, we discuss the recent epidemiological, gene-environment interaction, microbiome and animal studies that have explored the relationship between diet and the risk of IBD. In addition, we highlight the limitations of these prior studies, in part by explaining their contradictory findings, and review future directions.

Figure 1 |. The pathophysiology of inflammatory bowel disease.

The pathophysiology of inflammatory bowel disease (IBD) is related to an inappropriate host immune response to commensal bacteria in genetically susceptible individuals. Environmental influences alter the composition of the gut microbiota and change mucosal barrier function. Dendritic cells and macrophages are antigen-presenting cells involved in activation of T cells and production of pro-inflammatory cytokines. Dendritic cells are activated through the the recognition of luminal antigens by Toll-like receptors (TLRs) and are in turn necessary for activation of naïve T cells. Macrophages could also serve as antigen-presenting cells once stimulated by INFγ secreted by T cells. Activated macrophages and dendritic cells also produce pro-inflammatory cytokines including TNF-alpha, IL212, and IL23. The result of this pro-inflamamtory cytokine cascade is loss of immune tolerance to commensal bacteria and the production of pro-inflammatory cytokines by activated T cells. INF, Inteferon-gamma;TNF, tumour necrosis factor; IL-312, interleukin-12; IL-23, interleukin-23;

Figure 2 |. Potential mechanisms underpinning the relationship between diet and inflammatory bowel disease.

As compared to Mediterranean diet which is characterized by high intake of fruits and vegetables, whole grains, and sea good, western diet characterized by high intake of red and processed meat, saturated fat, and refined sugar is widely thought to increase risk of IBD. Although the exact mechanism underpinning the association between diet and risk of IBD is unknown, a number of plausible mechanisms have been proposed. Specifically, western diet has been linked to changes in the gut microbiome and epithelial barrier function and appears to have a direct impact on the immune function triggering a pro-inflammatory environment characterized by an imbalance in the T_H17/T_reg axis.

Figure 3 |. The complex causal relationship between diet and inflammatory bowel disease-.

The pathophysiology of IBD is thought to be related to inappropriate immune response to the gut microbiome in the genetically susceptible host. The composition of the gut microbiome is primarily dictated by environmental determinants particularly diet and the host genetics. In turn dietary factors may have differential influence on the immune function and risk of IBD according to the host genetics. Studies examining the role of diet, gut microbiome, and host genetics on risk of IBD are particularly complicated by the reciprocal effect of active disease on the gut microbiome and individuals’ dietary choices.