UK IND-ISPG Studentship: How does vitamin D maintain gut health

Lead Research Organisation: Quadram Institute Bioscience
Department Name: Contracts

Abstract

Convincing evidence exists for the preventive effect of increased vitamin D status on colon cancer risk. However, since a significant proportion of the UK population is vitamin D deficient, particularly during the winter months, this represents a significant public health concern. Colon carcinogenesis is associated with altered epigenetic modifications, such as DNA methylation, which modulate the expression of genes important for controlling cancer development. We have recently demonstrated that the abnormal DNA methylation of these genes in the healthy human colon is induced during ageing but the rate of its acquisition is significantly influenced by vitamin D status. Vitamin D has previously been suggested to affect cancer risk via postulated mechanisms that include effects on cell signalling pathways, modulation of innate immune responses and promoting epithelial barrier integrity. This project will therefore explore the hypothesis that vitamin D influences colon cancer risk by modifying the epigenetic regulation of genes involved in these processes. The project will utilise a recently developed colonic epithelial stem cell culture system to elucidate the mechanisms by which vitamin D modulates abnormal, age-related DNA methylation and determine the consequences these changes have for gene expression, signalling pathways and ultimately the cell.

Publications

10 25 50
 
Description It has been shown for the first time that treating colonic stem cells with calcitriol (the bioactive form of vitamin D) causes changes in the methylation status of genes controlling cell growth and proliferation. Methylated genes are typically silenced (not active) and silenced genes are associated with higher cancer risk, so this research provides evidence that vitamin D may have a role to play in preventing the development and progression of bowel cancer.
Exploitation Route The research within this project was undertaken in vitro and using novel cultured models of the human colon, and the findings would need validating by showing that similar effects of vitamin D on methylation status of genes could be achieved in humans. For example, cross-sectional studies could be done to look for associations between individual's vitamin D status and the methylation of genes in the colon, or a placebo-controlled vitamin D intervention study could be conducted to see if increasing vitamin D status results in changes in gene methylation.
Sectors Agriculture, Food and Drink,Healthcare