Nutritional influences in selected gastrointestinal diseases

Abstract

Nutritional factors, as sources of luminal antigens, have been thought to be important factors in the immunopathogenesis of numerous gastrointestinal diseases. In some diseases, the role of the nutritional component is causal in the susceptible host. Such diseases include celiac disease, a common heritable chronic inflammatory condition of the small intestine induced by dietary wheat, rye and barley, in susceptible individuals. Specific HLA-DQ2 and HLA-DQ8 risk alleles are necessary, but not sufficient, for disease development. The well-defined role of HLA-DQ heterodimers encoded by these alleles is to present cereal peptides to CD4+ T cells, activating an inflammatory immune response in the intestine. Genome-wide association studies have been performed which identified the IL2-IL21 risk locus and other genes with immune functions and key roles in thymic T-cell selection. Another example for this group is Wilson's disease, an autosomal recessive disorder of copper metabolism caused by mutation of the ATP7B gene, resulting in a defect of biliary copper excretion and toxic accumulation in the body, especially in the liver, brain and cornea, resulting in hepatic and/or neurological symptoms. In other diseases, however, the association is less well established. In such endeavor, epidemiological observations may become a valuable part of the overall investigations aimed at identifying dietary factors, which are involved in the initiation and perpetuation of the specific disease. As an example, relationships between nutrition and colorectal cancer have been hypothesized early on (e.g. folate, calcium, vitamin D, red meat). Similarly, intake of certain diet constituents like fat, refined sugar, fruits, vegetables and fiber was reported to be associated with the expression of inflammatory bowel diseases. In addition, in children with active Crohn's disease, enteral nutrition was found to be equally effective as corticosteroids in induction of remission, with mucosal healing induced by downregulation of mucosal pro-inflammatory cytokine profiles in both the ileum and the colon after enteral nutrition. However, the particular effect of the consumption of each type of food remains questionable in most cases, at least in part because of insufficient data and serious methodological limitations (e.g. recall bias, heterogeneity between collected data, lack of correction for covariates, difficulties in double blinding).