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Lookup NU author(s): Dr Fiona MalcomsonORCiD, Dr Naomi Willis, Iain McCallum, Dr Long Xie, Idoya Ibero, Wing Leung, Seamus Kelly, David Bradburn, Professor John Mathers
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
Background: Hyperactive Wnt signaling is frequently observed in colorectal cancer. Higher intakes of dietary fiber [nondigestible carbohydrates (NDCs)] and the fermentation product butyrate are protective against colorectal cancer and may exert their preventative effects via modulation of the Wnt pathway.Objectives: We investigated the effects of supplementing healthy individuals with 2 NDCs [resistant starch (RS) and polydextrose] on fecal calprotectin concentrations and Wnt pathway related gene expression. In addition, we determined whether effects on secreted frizzled-related protein 1 (SFRP1) expression are mediated via the epigenetic mechanisms DNA methylation and micro RNA expression.Design: In a randomized, double-blind, placebo-controlled trial (the Dietary Intervention, Stem cells and Colorectal Cancer (DISC) Study), 75 healthy participants were supplemented with RS and/or polydextrose or placebo for 50 d in a 2 X 2 factorial design. Pre and postintervention stool samples and rectal mucosal biopsies were collected and used to quantify calprotectin and expression of 12 Wnt-related genes, respectively. The expression of 10 microRNAs predicted to target SFRP1 was also quantified by quantitative reverse transcriptase-polymerase chain reaction, and DNA methylation was quantified at 7 CpG sites within the SFRP1 promoter region by pyrosequencing.Results: NDC supplementation did not affect fecal calprotectin concentration. SFRP1 mRNA expression was reduced by both RS (P = 0.005) and polydextrose (P = 0.053). RS and polydextrose did not affect SFRP1 methylation or alter the expression of 10 microRNAs predicted to target SFRP1. There were no significant interactions between RS and polydextrose.Conclusions: RS and polydextrose supplementation did not affect fecal calprotectin concentrations. Downregulation of SFRP1 with RS and polydextrose could result in increased Wnt pathway activity. However, effects on Wnt pathway activity and downstream functional effects in the healthy large-bowel mucosa remain to be investigated.
Author(s): Malcomson FC, Willis ND, McCallum I, Xie L, Ibero-Baraibar I, Leung WC, Kelly S, Bradburn DM, Belshaw NJ, Johnson IT, Mathers JC
Publication type: Article
Publication status: Published
Journal: American Journal of Clinical Nutrition
Year: 2017
Volume: 105
Issue: 2
Pages: 400-410
Print publication date: 01/02/2017
Online publication date: 11/01/2017
Acceptance date: 05/12/2016
Date deposited: 13/04/2017
ISSN (print): 0002-9165
ISSN (electronic): 1938-3207
Publisher: American Society for Nutrition
URL: https://doi.org/10.3945/ajcn.116.135657
DOI: 10.3945/ajcn.116.135657
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