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Effects of supplementation with nondigestible carbohydrates on fecal calprotectin and on epigenetic regulation of SFRP1 expression in the large-bowel mucosa of healthy individuals

Lookup NU author(s): Dr Fiona Malcomson, Dr Naomi Willis, Iain McCallum, Dr Long Xie, Idoya Ibero, Wing Leung, Seamus Kelly, David Bradburn, Professor John Mathers

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

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.


Publication metadata

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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