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

Fiona C. Malcomson, Naomi D. Willis, Iain McCallum, Long Xie, Nitin Shivappa, Michael D. Wirth, James R. Hébert, Betul Kocaadam-Bozkurt, Aycil Özturan-Sirin, Seamus B. Kelly, D. Michael Bradburn, Nigel J. Belshaw, Ian T. Johnson, John C. Mathers

Research output: Contribution to journalArticlepeer-review

Abstract

Inflammation drives colorectal cancer development, and colorectal cancer risk is influenced by dietary factors, including dietary fiber. Hyperactive WNT signaling occurs in colorectal cancer and may regulate inflammation. This study investigated (i) relationships between the inflammatory potential of diet, assessed using the Energy-adjusted Dietary Inflammatory Index (E-DII), and markers of WNT signaling, and (ii) whether DII status modulated the response to supplementation with two types of dietary fiber. Seventy-five healthy participants were supplemented with resistant starch and/or polydextrose (PD) or placebo for 50 days. Rectal biopsies were collected before and after 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 fecal calprotectin concentrations were quantified. hsCRP concentration was significantly greater in participants with higher E-DII scores [least square means (LSM) 4.7 vs. 2.4 mg/L, P = 0.03]. Baseline E-DII score correlated with FOSL1 (b = 0.503, P = 0.003) and WNT11 (b = 0.472, P = 0.006) expression, after adjusting for age, gender, body mass index, endoscopy procedure, and smoking status. WNT11 expression was more than 2-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 proinflammatory diets were associated with altered WNT signaling 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 signaling in rectal tissue of healthy individuals.

Original languageEnglish
Pages (from-to)337-346
Number of pages10
JournalCancer Prevention Research
Volume14
Issue number3
Early online date28 Oct 2020
DOIs
Publication statusPublished - Mar 2021

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