Award details

Nutrition and intestinal health

Reference	BBS/E/F/00042242
Principal Investigator / Supervisor	Dr Elizabeth Lund
Co-Investigators / Co-Supervisors
Institution	Quadram Institute Bioscience
Department	Quadram Institute Bioscience Department
Funding type	Research
Value (£)	412,147
Status	Completed
Type	Institute Project
Start date	01/04/2006
End date	01/04/2009
Duration	36 months

Abstract

The preservation of intestinal mucosal integrity depends on maintaining the balance between epithelial cell proliferation and apoptosis. The underlying hypothesis in this project is that dietary factors can modify this homeostatic process with the potential to enhance intestinal health and minimize the detrimental affects of ageing and damaging stimuli resulting from chronic inflammation. It focuses on the impact of essential fatty acids on gene expression and mucosal cell signalling, involvement of nuclear receptors, and interaction with probiotic bacteria in relation to mucosal homeostasis. We have shown that n-3 polyunsaturated fatty acids (PUFAs) down-regulate mitosis and up-regulate apoptosis in intestinal crypts and that redox tone is involved in this process. We now wish to test the hypothesis that signalling via nuclear receptors PPAR and RxR modifies gene expression, assessed using focussed transcriptomic analysis of previously acquired data, and studies using specific agonists and antogonists in in vivo and in vitro models. The relative roles of redox and nuclear receptor mediated regulation of transcription by PUFAs will be investigated in these models, and in colonic biopsies obtained as part of an ongoing human intervention study with oil-rich fish. Taqman based assays for key genes of interest will be developed to allow more quantitative and sensitive analysis of samples. The colonic mucosa is a complex tissue containing colonocytes, fibroblasts and hematopoietic cells. Chronic inflammation such as that occurring as a result of obesity, colonic bacteria and inflammatory bowel disease is associated with increased colorectal tumourogenesis, probably as a result of pro-mitotic/anti-apoptotic cytokine mediated responses. We will establish experimental models to explore the effects of PUFA on the balance between cell proliferation and apoptosis in this complex system.

Summary

unavailable

Committee	Closed Committee - Agri-food (AF)
Research Topics	Ageing, Diet and Health, Immunology, Microbiology
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

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