title: Effects of supplementation with nondigestible carbohydrates on fecal calprotectin and on epigenetic regulation of SFRP1 expression in the large-bowel mucosa of healthy individuals.
abstract: 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.
  
  
  
  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 microRNA expression.
  
  
  
  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 × 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.
  
  
  
  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.
  
  
  
  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. The DISC Study was registered at clinicaltrials.gov as NCT01214681.
authors.affiliation: Human Nutrition Research Centre, Institute of Cellular Medicine, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne, United Kingdom.
authors.forename: Fiona C
authors.identifier: 0000-0001-5072-7644
authors.initials: FC
authors.lastname: Malcomson
authors.affiliation: Human Nutrition Research Centre, Institute of Cellular Medicine, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne, United Kingdom.
authors.forename: Naomi D
authors.initials: ND
authors.lastname: Willis
authors.affiliation: Human Nutrition Research Centre, Institute of Cellular Medicine, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne, United Kingdom.
authors.forename: Iain
authors.initials: I
authors.lastname: McCallum
authors.affiliation: Human Nutrition Research Centre, Institute of Cellular Medicine, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne, United Kingdom.
authors.forename: Long
authors.initials: L
authors.lastname: Xie
authors.affiliation: Human Nutrition Research Centre, Institute of Cellular Medicine, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne, United Kingdom.
authors.forename: Idoia
authors.initials: I
authors.lastname: Ibero-Baraibar
authors.affiliation: Institute of Food Research, Norwich Research Park, Norwich, Norfolk, United Kingdom.
authors.forename: Wing C
authors.initials: WC
authors.lastname: Leung
authors.affiliation: Northumbria Healthcare National Health Service Foundation Trust, North Shields, United Kingdom; and.
authors.forename: Seamus
authors.initials: S
authors.lastname: Kelly
authors.affiliation: Northumbria Healthcare National Health Service Foundation Trust, Ashington, United Kingdom.
authors.forename: D Michael
authors.initials: DM
authors.lastname: Bradburn
authors.affiliation: Institute of Food Research, Norwich Research Park, Norwich, Norfolk, United Kingdom.
authors.forename: Nigel J
authors.initials: NJ
authors.lastname: Belshaw
authors.affiliation: Institute of Food Research, Norwich Research Park, Norwich, Norfolk, United Kingdom.
authors.forename: Ian T
authors.initials: IT
authors.lastname: Johnson
authors.affiliation: Human Nutrition Research Centre, Institute of Cellular Medicine, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne, United Kingdom; john.mathers@newcastle.ac.uk.
authors.forename: John C
authors.identifier: 0000-0003-3406-3002
authors.initials: JC
authors.lastname: Mathers
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019175:DNA Methylation; D004040:Dietary Carbohydrates / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004311:Double-Blind Method; D015536:Down-Regulation; D044127:Epigenesis, Genetic; D005243:Feces / Q000737:chemistry*; D005260:Female; D005936:Glucans / Q000737:chemistry; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism*; D039841:Leukocyte L1 Antigen Complex / Q000737:chemistry*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013213:Starch / Q000737:chemistry; D060449:Wnt Signaling Pathway; D055815:Young Adult; D000094742:Secreted Frizzled-Related Proteins
chemical_list: D004040:Dietary Carbohydrates; D005936:Glucans; D036341:Intercellular Signaling Peptides and Proteins; D039841:Leukocyte L1 Antigen Complex; D008565:Membrane Proteins; D035683:MicroRNAs; D012333:RNA, Messenger; D013213:Starch; C117636:SFRP1 protein, human; D000094742:Secreted Frizzled-Related Proteins; C033375:polydextrose
keywords: Wnt signaling; calprotectin; colorectal cancer; epigenetics; nondigestible carbohydrates