Diet-Associated Inflammation Modulates Inflammation and WNT Signaling in the Rectal Mucosa, and the Response to Supplementation with Dietary Fiber

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dc.authoridShivappa, Nitin/0000-0003-0441-8896
dc.authoridXIE, LONG/0000-0002-2138-888X
dc.authoridMathers, John/0000-0003-3406-3002
dc.authoridMalcomson, Fiona/0000-0001-5072-7644
dc.authoridOzturan Sirin, Aycil/0000-0003-2145-3626
dc.authoridKocaadam Bozkurt, Betul/0000-0002-9058-4630
dc.authoridJohnson, Ian/0000-0002-2353-4609
dc.authorwosidHebert, James/JEF-1061-2023
dc.authorwosidShivappa, Nitin/X-2215-2018
dc.authorwosidXIE, LONG/HOH-1079-2023
dc.authorwosidJohnson, Ian T/D-2892-2012
dc.authorwosidHebert, James R/IUO-5628-2023
dc.authorwosidWirth, Michael/C-6330-2013
dc.authorwosidMalcomson, Fiona/KMY-7212-2024
dc.contributor.authorMalcomson, Fiona C.
dc.contributor.authorWillis, Naomi D.
dc.contributor.authorMcCallum, Iain
dc.contributor.authorXie, Long
dc.contributor.authorShivappa, Nitin
dc.contributor.authorWirth, Michael D.
dc.contributor.authorHebert, James R.
dc.date.accessioned2024-06-12T11:17:52Z
dc.date.available2024-06-12T11:17:52Z
dc.date.issued2021
dc.departmentTrakya Üniversitesien_US
dc.description.abstractInflammation 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 DIE 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 calpmtectin concentrations were quantified. hsCRP concentration was significantly grater 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 (beta = 0.503, P = 0.003) and WNT11 (beta = 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. Prevention Relevance: Our finding that more inflammatory dietary components may impact large bowel health through effects on a well-recognized pathway involved in cancer development will strengthen the evidence base for dietary advice to help prevent bowel cancer.en_US
dc.description.sponsorshipBBSRC Diet and Health Research Industry Club (DRINC) [BB/H005013/1]; Northumbria NHS Foundation Trust; Newcastle University Centre for Ageing and Vitality - Medical Research Council; BBSRC as part of the cross-council Lifelong Health and Wellbeing Initiative [MR/L016354/1]; Wellcome Trust; Wellcome Trust Broadening Our Horizons scheme; BBSRC [BB/H005013/1] Funding Source: UKRI; MRC [MR/L016354/1] Funding Source: UKRIen_US
dc.description.sponsorshipThis 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.en_US
dc.identifier.doi10.1158/1940-6207.CAPR-20-0335
dc.identifier.endpage346en_US
dc.identifier.issn1940-6207
dc.identifier.issn1940-6215
dc.identifier.issue3en_US
dc.identifier.pmid33115783en_US
dc.identifier.scopus2-s2.0-85102099982en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.startpage337en_US
dc.identifier.urihttps://doi.org/10.1158/1940-6207.CAPR-20-0335
dc.identifier.urihttps://hdl.handle.net/20.500.14551/24875
dc.identifier.volume14en_US
dc.identifier.wosWOS:000625890600005en_US
dc.identifier.wosqualityQ3en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherAmer Assoc Cancer Researchen_US
dc.relation.ispartofCancer Prevention Researchen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectColorectal-Canceren_US
dc.subjectResistant Starchen_US
dc.subjectGene-Expressionen_US
dc.subjectProteinen_US
dc.subjectIndexen_US
dc.subjectRisken_US
dc.subjectMechanismsen_US
dc.subjectProliferationen_US
dc.subjectPreventionen_US
dc.subjectMutationsen_US
dc.titleDiet-Associated Inflammation Modulates Inflammation and WNT Signaling in the Rectal Mucosa, and the Response to Supplementation with Dietary Fiberen_US
dc.typeArticleen_US

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