Nutritional Therapy of IBD - Integrating Environmental and Bacterial Data

Crohn’s disease (CD) is caused by a combination of environmental, genetic innate immune and microbial factors. Genetic studies in very large cohorts have found that genetic alterations can only explain 13% of the incidence of the disease of CD, and even less in UC. Coupled with the rising incidence, these data suggest a significant role for unknown environmental factors in pathogenesis. The most significant research gap appears to be identification and targeting of upstream events and in particular treatable environmental factors. Dietary factors are among the strongest candidates for environmental factors, along with early exposure to factors that alter the microbiome. There is a surge of IBD that accompanies Westernization, which includes exposure to western diet and industrialized food. Multiple studies raise the possibility that a variety of dietary factors may be associated with Crohn’s disease. These include epidemiologic studies demonstrating both harmful and protective effects of different dietary components, and rodent models that demonstrate the ability of several dietary factors to induce dysbiosis, increase colonization with Adherent Invasive E Coli and or bile acid dependent bacteria, or increase intestinal permeability. The strongest case for an effect of dietary exposure as an environmental factor is the high remission rate observed with Exclusive Enteral Nutrition (EEN) in children with CD. The magnitude of the effect may be dependent on exclusion of regular free diet. A recent study has shown that EEN does not appear to act by increasing diversity or short chain fatty acids as previously thought. Under normal circumstances, the mucous layer, intestinal epithelial cells, Paneth cells and the tight junctions serve as an efficient barrier to exclude viable enteric bacteria from penetrating or interacting with lamina propria immune cells. Multiple dietary components have been shown to change the microbiome by reducing diversity and allowing the growth of pathobionts in rodent models. Others have been shown to deplete the mucous layer, increase migration of bacteria through trans- cellular or paracellular pathways, increase adhesion to the epithelium, increase intestinal permeability (IP) and translocation of Adherent Invasive E.Coli. The case for diet as an environmental cause in UC has been weaker. However recent studies in animal models and human subjects have demonstrated the presence of dysbiosis and an altered mucous layer that is accompanied by an alteration in metabolic pathways of resident bacteria. This altered metabolic function may be associated with exposure to certain dietary components, and leaves the door open for future dietary manipulation of this disease as well.