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Diet-associated inflammation modulates inflammation and WNT signaling in the rectal mucosa, and the response to supplementation with dietary fibre

Lookup NU author(s): Dr Fiona MalcomsonORCiD, Dr Naomi Willis, Iain McCallum, Dr Long Xie, Dr Betul Kocaadam, Dr Aycil Ozturan, Seamus Kelly, David Bradburn, Professor John Mathers

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This is the authors' accepted manuscript of an article that has been published in its final definitive form by American Association for Cancer Research, 2021.

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Abstract

Inflammation drives colorectal cancer (CRC) development and CRC risk is influenced by dietary factors, including dietary fibre. Hyperactive WNT signalling occurs in CRC and may regulate inflammation. This study investigated i) relationships between the inflammatory potential of diet, assessed using the Energy-adjusted Dietary Inflammatory Index (E-DIITM), and markers of WNT signalling, and ii) whether DII status modulated the response to supplementation with two types of dietary fibre. Seventy-five healthy participants were supplemented with resistant starch (RS) and/or polydextrose (PD) or placebo for 50 days. Rectal biopsies were collected pre and post-intervention and used to assess WNT pathway gene expression and crypt cell proliferation. E-DII scores were calculated from food frequency questionnaire data. High-sensitivity C-reactive protein (hsCRP) and faecal calprotectin concentrations were quantified. hsCRP concentration was significantly greater in participants with higher E-DII scores (least square means (LSM) 4.7 vs. 2.4mg/L, P=0.03). Baseline E-DII score correlated with FOSL1 ( 0.503, P=0.003) and WNT11 (0.472, P=0.006) expression, after adjusting for age, gender, BMI, endoscopy procedure and smoking status. WNT11 expression was more than two-fold greater in individuals with higher E-DII scores (LSM 0.131 vs. 0.059, P=0.002). Baseline E-DII modulated the effects of PD supplementation on FOSL1 expression (P=0.04).More pro-inflammatory diets were associated with altered WNT signalling and appeared to modulate the effects of PD supplementation on expression of FOSL1.This is the first study to investigate relationships between the E-DII and molecular markers of WNT signalling in rectal tissue of healthy individuals.

Publication metadata

Author(s): Malcomson FC, Willis ND, McCallum I, Xie L, Shivappa N, Wirth MD, Hébert JR, Kocaadam-Bozkurt B, Özturan-Sirin A, Kelly SB, Bradburn DM, Belshaw NJ, Johnson IT, Mathers JC

Publication type: Article

Publication status: Published

Journal: Cancer Prevention Research

Year: 2021

Volume: 14

Issue: 3

Pages: 337-346

Print publication date: 01/03/2021

Online publication date: 28/10/2020

Acceptance date: 22/10/2020

Date deposited: 11/11/2020

ISSN (print): 1940-6207

ISSN (electronic): 1940-6215

Publisher: American Association for Cancer Research

URL: https://doi.org/10.1158/1940-6207.CAPR-20-0335

DOI: 10.1158/1940-6207.CAPR-20-0335

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