Circulating Biomarkers of Gut Barrier Function: Correlates and Nonresponse to Calcium Supplementation among Colon Adenoma Patients.
Circulating Biomarkers of Gut Barrier Function: Correlates and Nonresponse to Calcium Supplementation among Colon Adenoma Patients.
复制标题
DOI：
10.1158/1055-9965.epi-15-0488
复制
发表时间：
2016-02
期刊：
影响因子：
--
通讯作者：
Fedirko V
中科院分区：
文献类型：
--
作者：
Yang B;Bostick RM;Tran HQ;Gewirtz AT;Campbell PT;Fedirko V
肠道屏障功能障碍会导致多种胃肠道疾病，包括结直肠癌，但与肠道通透性过高相关的因素在人类中的研究很少。我们在一项随机、双盲、安慰剂对照临床试验 (n = 193) 中，在 4 个月的治疗期内，测试了两种剂量的钙（1.0 或 2.0 g/d）对肠道通透性循环生物标志物（抗鞭毛蛋白和抗脂多糖 [LPS] 免疫球蛋白 [Igs]，通过 ELISA 测量）的影响，并评估了与这些生物标志物基线水平相关的因素。与腰围最低性别特异性三分位相比，男性抗鞭毛蛋白 IgA 和抗 LPS IgA 的基线浓度在统计学上分别显着较高，分别为 11.8% 和 14.1%，体重指数 (BMI) ≥ 35 kg/m2 的人群分别高出 31.3% 和 39.8%，腰围最低的性别特定三分位数的人群中高出 19.9% 和 22.0%。血浆 C 反应蛋白上三分位女性的综合渗透性评分（所有四种生物标志物的光密度总和）高出 24.3%（ptrend < 0.01）。我们发现补充钙对抗鞭毛蛋白或抗 LPS Igs 没有明显影响。我们的结果表明：1）男性和肥胖程度较高的人可能具有更大的肠道通透性，2）肠道通透性和全身炎症可能直接相关，3）补充钙可能不会在四个月内改变肠道通透性生物标志物的循环水平。我们的研究结果可能会增进对影响肠道通透性的因素的理解，从而为结直肠癌和其他健康结果风险的可治疗生物标志物的开发提供信息。
Gut barrier dysfunction contributes to several gastrointestinal disorders, including colorectal cancer, but factors associated with intestinal hyperpermeability have been minimally studied in humans. We tested the effects of two doses of calcium (1.0 or 2.0 g/d) on circulating biomarkers of gut permeability (anti-flagellin and anti-lipopolysaccharide [LPS] immunoglobulins [Igs], measured via ELISA) over a 4-month treatment period among colorectal adenoma patients in a randomized, double-blinded, placebo-controlled clinical trial (n = 193), and evaluated factors associated with baseline levels of these biomarkers. Baseline concentrations of anti-flagellin IgA and anti-LPS IgA were, respectively, statistically significantly proportionately higher by 11.8% and 14.1% among men, 31.3% and 39.8% among those with a body mass index (BMI) ≥ 35 kg/m2, and 19.9% and 22.0% among those in the upper relative to the lowest sex-specific tertile of waist circumference. A combined permeability score (the summed optical densities of all four biomarkers) was 24.3% higher among women in the upper tertile of plasma C-reactive protein (ptrend < 0.01). We found no appreciable effects of supplemental calcium on anti-flagellin or anti-LPS Igs. Our results suggest that 1) men and those with higher adiposity may have greater gut permeability, 2) gut permeability and systemic inflammation may be directly associated with one another, and 3) supplemental calcium may not modify circulating levels of gut permeability biomarkers within four months. Our findings may improve understanding of the factors that influence gut permeability to inform development of treatable biomarkers of risk for colorectal cancer and other health outcomes.