IBD and Diet, the Role of Foods, and Genetics

A recent article in Medscape (Expert Rev Clin Immunol. 2013;9(8):735-747.) looked at the role of foods in the management of IBD. The author Lynette Ferguson summarised some of the key areas, and this summary is a synopsis of her paper.

Inflammatory bowel disease includes ulcerative colitis and Crohn’s disease, which are both inflammatory disorders of the gastrointestinal tract. Both types of inflammatory bowel disease have a complex aetiology, resulting from a genetically determined susceptibility interacting with environmental factors, including the diet and gut microbiota. Genome Wide Association Studies have implicated more than 160 single-nucleotide polymorphisms in disease susceptibility. Consideration of the different pathways suggested to be involved implies that specific dietary interventions are likely to be appropriate, dependent upon the nature of the genes involved. Epigenetics and the gut microbiota are also responsive to dietary interventions. Nutrigenetics may lead to personalized nutrition for disease prevention and treatment, while nutrigenomics may help to understand the nature of the disease and individual response to nutrients.

Epigenetics provides a mechanism for regulating otherwise heritable changes in gene expression, but without changes to the coding DNA sequence

Diet has a significant impact on the development and progression of IBD. However, it is apparent that no single dietary regime is beneficial to all patients with the disease. The most prudent dietary advice is likely to relate to genotype. By 2010, it was apparent that more than 90 genetic variants were involved in disease susceptibility, and a number of these had clear mechanistic associations with diet. Important developments since 2010, especially involving the development of a highly focused gene chip for autoimmune diseases such as IBD (the immunochip) have increased this number to more than 160 genes, and also increased our understanding of the number of pathways likely to be involved in disease susceptibility. Again specific dietary recommendations may associate with these newly discovered genes. For example, vitamin D and VDR polymorphisms are being increasingly recognized as important in IBD pathogenesis.

As well as genetic variants, two other factors are becoming increasingly apparent from the recent literature. IBD susceptibility, especially in animal models, has emerged after epigenetic changes. Epigenetics, as DNA methylation, is known to be modulated by micro-nutrients interacting in one carbon metabolism. Histone deacetylase (HDAC) inhibition is also recognised as a key target, which may be responsive to various phytochemicals in the diet. Modulation of the gut microbiota may be especially important among the various effects of dietary manipulation. Although there have been some interesting results on UC and a mixed probiotic, most studies considering effects of probiotics and prebiotics on IBD have proved generally disappointing. It would appear that modulation of macro- and micronutrients, and dietary phytochemicals, may produce more sustainable effects.

Key Issues

• Inflammatory bowel diseases, including Crohn’s disease (CD) or ulcerative colitis (UC), are increasing in incidence in the western world.
• The pathogenesis of these diseases, especially CD, involves an inflammatory response targeted at the commensal microflora residing in the intestinal tract of a genetically susceptible host.
• This genetic susceptibility is impacted, both positively and negatively by diet.
• Genes associated with susceptibility to CD fall primarily into five key pathways. These include innate pattern recognition receptors (NOD1, NOD2, TLR4), autophagy (ATG16L1, IRGM), the differentiation of Th17-lymphocytes (IL-23R, JAK2, STAT3), orchestration of the secondary immune response (HLA region, TNFSF15, PTPN2and IL-12B) and the maintenance of epithelial barrier integrity (IBD5, DLG5, ITLN1, and so on).
• There is overlap among many but not all of the genes in CD and UC; the latter three but not the former two of the pathways identified above would appear important in UC.
• Knowledge of the affected genes, coupled with in vitro, animal or human studies, leads to some potentially advantageous foods for both diseases.
• For individuals carrying genes involved in innate pattern recognition receptors or for autophagy, regimes that modulate the bacterial flora, including probiotics and prebiotics, may be beneficial, as may vitamin D.
• For individuals carrying genes in differentiation of Th-17 lymphocytes or orchestrating secondary immune response, long-chain polyunsaturated fatty acids, or various polyphenols including curcumin or epigallocatechin gallate may play a useful role.
• A range of flavonoids are known to modulate the efficacy of epithelial barrier function; quercetin, epigallocatechin gallate, genistein, quercetin and myricetin.
• Key micro nutrients include, Zinc, Vitamin D, Folate, B12 and Selenium
• long-chain omega-3 PUFA are also helpful in some
• Clinical trials in this area are urgently indicated.

Epigenetics & IBD

Epigenetics research may be essential to understanding the potential role of environment, including diet, in IBD. Jenke and Zilbauer reviewed the results of recent studies on epigenetic events in IBD, considering both the challenges and also the opportunities for future research. They summarized the accumulating evidence that epigenetics may modulate some of the effects of genetic predisposition, as well as environment and intestinal microbiota on the pathogenesis of IBD.[1]

Commentary

IBD is a complex illness, increasing in frequency and requires careful consideration in terms of nutrient support and intervention. Without gene assays it can be a trial and error strewn approach, but cautious evolution of food selection and micro-nutrient supplementation can provide significant improvements in functionality.

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