Diet-Associated Inflammation Modulates Inflammation and WNT Signaling in the Rectal Mucosa, and the Response to Supplementation with Dietary Fiber.
Diet-Associated Inflammation Modulates Inflammation and WNT Signaling in the Rectal Mucosa, and the Response to Supplementation with Dietary Fiber.
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DOI：
10.1158/1940-6207.capr-20-0335
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发表时间：
2021-03
期刊：
影响因子：
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通讯作者：
Mathers JC
中科院分区：
文献类型：
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作者：
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
炎症驱动结直肠癌（CRC）的发展，CRC的风险受到饮食因素的影响，包括膳食纤维。过度活跃的WNT信号发生在结直肠癌中，并可能调节炎症。本研究调查了i)饮食的炎症潜能（使用能量调节饮食炎症指数（E-DII™）评估）与WNT信号标志物之间的关系，以及ii) DII状态是否调节了对补充两种膳食纤维的反应。75名健康的参与者补充了抗性淀粉（RS）和/或聚葡萄糖（PD）或安慰剂50天。在干预前后收集直肠活检，用于评估WNT通路基因表达和隐窝细胞增殖。E-DII评分根据食物频率问卷数据计算。测定高敏c反应蛋白（hsCRP）和粪钙保护蛋白浓度。E-DII评分较高的受试者hsCRP浓度显著较高（最小二乘法平均值（LSM） 4.7 vs. 2.4mg/L， P=0.03）。在调整年龄、性别、BMI、内镜检查程序和吸烟状况后，基线E-DII评分与FOSL1 （β= 0.503， P=0.003）和WNT11 （β=0.472， P=0.006）表达相关。在E-DII评分较高的个体中，WNT11的表达量高出两倍以上（LSM为0.131比0.059，P=0.002）。基线E-DII调节PD补充对FOSL1表达的影响（P=0.04）。更多的促炎饮食与WNT信号的改变有关，并似乎调节PD补充对FOSL1表达的影响。这是第一个研究健康个体直肠组织中E-DII与WNT信号分子标记物之间关系的研究。
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-DII™), 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 (β= 0.503, P=0.003) and WNT11 (β=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.