Nutritional Therapy in Inflammatory Bowel Disease

Chen Sarbagili-Shabat; Rotem Sigall-Boneh; Arie Levine

Disclosures

Curr Opin Gastroenterol. 2015;31(4):303-308. 

In This Article

Dietary Components in Health and Disease: Animal Models

Previously published studies have highlighted the possible deleterious effect of animal fat, milk fat, iron and emulsifiers in IBD rodent models.[15–23] Martinez-Medina et al.[17] recently demonstrated that a high-fat, high-sugar diet led to dysbiosis and colonization with adherent invasive Escherichia coli (AIEC), depletion of the mucous layer and increased intestinal permeability in an IL10−/− knockout mouse. The effect of a high-fat diet was also reproduced in the TNFΔAre/wt mouse model of ileitis by comparing mice fed conventional chow or a high-fat diet.[19] Mice fed the high-fat diet developed increased intestinal permeability, generated Th17-driven dendritic cells and developed more severe ileitis. Gluten has also now been proposed to play a deleterious role in ileitis as well. Gluten can induce zonulin, which in turn increases small intestinal permeability.[24] In an elegant study by Wagner et al.[20] in the same mouse model, they compared the development of ileitis with standard chow, gluten-free chow or chow with added gluten. Exposure to chow containing gluten exacerbated ileitis, most likely by increasing the intestinal permeability. Two relatively new kids on the block in this growing list may connect diet and AIEC, a possible pathobiont in Crohn's disease. These bacteria can translocate across ileal epithelium, survive in macrophages and generate TNF-alpha, leading to granulomas. Strains of AIEC have been isolated from the ileum and the colon of control and Crohn's disease patients.[8,25] Maltodextrin was recently found to promote AIEC biofilms, and increase adhesion of AIEC strains to intestinal epithelial cells and macrophages via upregulation of type 1 pili expression.[26] Importantly, this mechanism does not require the usual ligand for attachment (CEACAM 6), suggesting that exposure to maltodextrin may allow AIEC to attach when it otherwise could not adhere to cells. Maltodextrin is a thickening and binding agent found in breakfast cereals as well as aspartame and sucralose, commonly used as artificial sweeteners. Iron and heme may be critical for the chain of events enabling AIEC penetration and survival in macrophages. Growth of AIEC required iron, and the enrichment of these strains with heme acquisition genes correlated with persistence in macrophages.[27] Red meat has also joined this list in rodent models, as it was recently found to promote inflammation in a dextran sulfate sodium (DSS) colitis model. Interestingly enough, the effect of red meat was ameliorated by resistant starch, one of the sources for butyrate production.[28]

Two recent studies have shed light on the potential benefits and mechanisms of n-butyrate, a product of bacterial fermentation of fibers and starches, on the innate immune system.[29,30]n-Butyrate was found to reduce the secretion of interleukin (IL)-6, IL-12 and nitric oxide synthase via a direct effect on the inhibition of deacetylation of histones,[29] and also found to induce differentiation of regulatory T cells.[30] However, it was ineffective in ameliorating colitis in a DSS model of colitis.[29]

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