Department of Physiological Sciences, Stellenbosch University, Stellenbosch, Private Bag X1 Matieland, 7602, South Africa.
Department of Internal Medicine, Stellenbosch University, Stellenbosch, Private Bag X1 Matieland, 7602, South Africa.
Sci Rep. 2020 May 29;10(1):8777. doi: 10.1038/s41598-020-65324-2.
Gut dysbiosis contributes to the development of a dysfunctional gut barrier, facilitating the translocation of bacteria and inflammagens, and is implicated in colorectal cancer (CRC) pathogenesis. Such 'leaky gut' conditions result in systemic inflammation, of which a hallmark is increased hypercoagulability. Fluorescence antibody confocal microscopy was used to determine circulating levels of lipopolysaccharide (LPS) in control and CRC populations. Here we showed that circulating levels of LPS are significantly elevated in the CRC population. We also showed that markers of inflammation and hypercoagulability are increased in this population. Furthermore, anomalous blood clotting and structural changes in blood components are presented. Importantly, the association between LPS levels, inflammation, and hematological dysfunction was analysed. Statistical regression models were applied to identify markers with strong association with CRC, and to investigate the correlation between markers. A core aim is enhanced biomarker discovery for CRC. We conclude that circulating LPS can promote systemic inflammation and contribute to the development of a pathological coagulation system, with resulting chronic inflammation and an activated coagulation system implicated in tumorigenesis. Blood-based screening tools are an emerging research area of interest for CRC screening. We propose the use of additional (novel) biomarkers to effectively screen for CRC.
肠道菌群失调导致肠道屏障功能障碍，促进细菌和炎症因子的易位，并与结直肠癌（CRC）的发病机制有关。这种“渗漏肠道”的情况会导致全身炎症，其特征之一是血液高凝状态增加。荧光抗体共聚焦显微镜用于检测对照和 CRC 人群中循环脂多糖（LPS）的水平。我们发现 CRC 人群中 LPS 的循环水平显著升高。我们还表明，该人群中炎症和血液高凝状态的标志物增加。此外，还呈现了血液成分的异常凝血和结构变化。重要的是，分析了 LPS 水平、炎症和血液学功能障碍之间的关联。应用统计回归模型来确定与 CRC 具有强关联的标志物，并研究标志物之间的相关性。一个核心目标是增强 CRC 的生物标志物发现。我们得出结论，循环 LPS 可促进全身炎症，并有助于病理性凝血系统的发展，导致慢性炎症和激活的凝血系统与肿瘤发生有关。基于血液的筛查工具是 CRC 筛查的一个新兴研究领域。我们建议使用额外（新型）生物标志物来有效筛查 CRC。
