盆腔恶性肿瘤患者放疗后肠道菌群变化与放射性肠炎的相关性研究

Clinical study on the correlation between intestinal flora changes and acute radiation enteritis in patients with pelvic malignant tumor after radiotherapy

目的:研究盆腔恶性肿瘤患者放疗后肠道菌群变化,并分析其与脂多糖(LPS)、肿瘤坏死子因子-α(TNF-α)、白细胞介素-1β(IL-1β)及高迁移率族蛋白B1(HMGB1)等炎症因子的相关性,探讨其在预测放射性肠炎中的临床价值。方法:选取2020年10月至2021年6月在徐州医科大学附属江阴临床学院收治的17例首次接受盆腔放疗患者,按照RTOG/EORTC放射反应分级标准分为无症状组、轻症组和重症组。采用16S rDNA测序法检测肠道菌群情况,酶联免疫吸附试验检测炎症因子水平,并进行相关性分析。结果:放疗后患者肠道菌群α多样性明显下降,且放疗前后组间β多样性也存在差异(Stress<0.1)。放疗前重症组患者粪便中Castellaniella属显著高于轻症组和无症状组(P<0.05)。随着放疗剂量累计炎症因子水平明显升高,且变化幅度与放射反应严重等级相关。放疗第3周重症组血清LPS、TNF-α、IL-1β及粪便HMGB1水平高于无症状组和轻症组,差异均有统计学意义(P<0.05)。代表肠道菌群丰度Chao1指数与血清LPS、TNF-α及粪便HMGB1呈负相关(r值分别为-0.655、-0.516、-0.623,均P<0.05);代表肠道菌群多样性Shannon指数与血清LPS呈负相关(r=-0.550,P<0.05)。结论:肠道菌群可能在放射性肠炎的发生、发展中起一定作用。通过检测患者肠道菌群Castellaniella可预测放射性肠炎严重程度,从而为预测及防治放射性肠损伤提供新的思路和方法。

Objective:To study the changes of intestinal flora in patients with pelvic malignant tumor during radiotherapy,and analyze its relationship with lipopolysaccharide(LPS),tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)and high mobility group protein B1(HMGB1),and to investigate its clinical value in predicting radiation enteritis.Methods:A total of 17 patients who received pelvic radiotherapy for the first time in Jiangyin Clinical College Affiliated to Xuzhou Medical University from October 2020 to June 2021 were selected and divided into asymptomatic group,mild group and severe group according to the standard of RTOG/EORTC.The intestinal flora was detected by DNA sequencing,and the level of serum inflammatory factors was detected by enzyme-linked immunosorbent assay.Results:The alpha diversity of intestinal flora decreased significantly after radiotherapy,and there were also differences in beta diversity between groups before and after radiotherapy(stress<0.1).Before radiotherapy,Castellaniella-genus in feces of the severe group was significantly higher than that of the mild group and the asymptomatic group(P<0.05).With the cumulative radiation dose,the level of inflammatory factors increased significantly,and the range of change was related to the severity of radiation reaction.The levels of serum LPS,TNF-α,IL-1βand fecal HMGB1 in the severe group in the third week of radiotherapy were significantly higher than those in the asymptomatic group and the mild group(P<0.05).The Chao1 index representing the abundance of intestinal flora was negatively correlated with LPS and TNF-αin serum and HMGB1 in feces(r=-0.655,-0.516,-0.623,all P<0.05);Shannon index,representing the diversity of intestinal flora,was negatively correlated with LPS in serum(r=-0.550,P<0.05).Conclusion:Intestinal flora may play a role in the occurrence and development of radiation enteritis.The severity of radiation enteritis can be predicted by detecting the castellaniella genus of intestinal flora,which provides a new idea and method for predicting and preventing radiation intestinal injury.