Chemoprevention of Colorectal Cancer: the Role of Non-digestible Carbohydrates
This project is designed to enhance understanding of links between food and the health of
the gut. The particular purpose of the project is to investigate the impact of a
well-defined intervention in human volunteers on a panel of novel, and established,
diet-related biomarkers of bowel cancer risk. We have developed a number of novel biomarkers
of diet-related CRC risk measured in colo-rectal mucosal biopsies (and in stool). These
biomarkers include differentially expressed proteins, DNA methylation markers and
inflammation markers. In our on-going BORICC Study we are investigating the relationships
between dietary exposure and nutritional status for these biomarkers in a cross-sectional
study. The next logical step in this research is to determine whether a selected panel of
the most promising biomarkers responds to a dietary intervention i.e. to test their utility
as biomarkers of GI health and potential as surrogate endpoints in future human studies.
We propose to use Hi-maize 260 and polydextrose (PD) as our model resistant starch (RS)
intervention agents. RS describes the fraction of dietary starch which is not digested in
the small bowel and which flows to the colon where it is a substrate for bacterial
fermentation. (Asp, 1996) PD is produced by the bulk melt polycondensation of glucose and
sorbitol to produce an oligosaccharide with a mean degree of polymerisation of 12 which is
resistant to mammalian GI enzymes and, like other RSs, is a substrate for bacterial
fermentation. (Auerbach, 2007) Both Hi-maize and PD are fermented (to a greater or lesser
extent) producing short-chain fatty acids (SCFA) including butyrate. (Asp, 1996) Butyrate
has beneficial effects on gut physiology and immune function including anti-inflammatory
effects. (Wächtershäuser, 2000; Dronamraju, 2009)
In the present project we will investigate the impact of PD and RS, as food-borne substrates
for delivery of butyrate, on biomarkers of bowel cancer risk.
Interventional
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Factorial Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention
Faecal calprotectin concentration
50 days
No
John Mathers, PhD
Study Director
Newcastle University
United Kingdom: National Health Service
002
NCT01214681
May 2010
December 2012
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