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

Malcomson, Fiona C., Willis, Naomi D., McCallum, Iain, Xie, Long, Shivappa, Nitin, Wirth, Michael D., Hébert, James R., Kocaadam-Bozkurt, Betul, Özturan-Sirin, Aycil, Kelly, Seamus B., Bradburn, D. Michael, Belshaw, Nigel J., Johnson, Ian T. and Mathers, John C. (2021) Diet-associated inflammation modulates inflammation and WNT signaling in the rectal mucosa, and the response to supplementation with dietary fiber. Cancer Prevention Research, 14 (3). pp. 337-346. ISSN 1940-6207

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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.

Item Type: Article
Additional Information: Funding Information: This work was supported by an award from the BBSRC Diet and Health Research Industry Club (DRINC; grant number BB/H005013/1) to J.C. Mathers, I.T. Johnson, N.J. Belshaw, and S.B. Kelly. I. McCallum was funded by a fellowship from Northumbria NHS Foundation Trust. The authors acknowledge further support from the Newcastle University Centre for Ageing and Vitality, which is funded by the Medical Research Council and BBSRC as part of the cross-council Lifelong Health and Wellbeing Initiative (grant no. MR/L016354/1) and from the Wellcome Trust. Further funding was awarded by the Wellcome Trust Broadening Our Horizons scheme to support the collaboration between Newcastle University and the University of South Carolina.
Uncontrolled Keywords: oncology,cancer research,sdg 3 - good health and well-being ,/dk/atira/pure/subjectarea/asjc/2700/2730
Faculty \ School: Faculty of Science > School of Environmental Sciences
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Depositing User: LivePure Connector
Date Deposited: 03 Nov 2020 11:49
Last Modified: 22 Oct 2022 07:24
DOI: 10.1158/1940-6207.CAPR-20-0335

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