Characterization of Gut Microbiota, Bile Acid Metabolism, and Cytokines in Intrahepatic Cholangiocarcinoma
Characterization of Gut Microbiota, Bile Acid Metabolism, and Cytokines in Intrahepatic Cholangiocarcinoma
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DOI：
10.1002/hep.30852
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发表时间：
2019-08-19
期刊：
影响因子：
13.5
通讯作者：
Lu, Yinying
中科院分区：
文献类型：
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作者：
Jia, Xiaodong;Lu, Shanshan;Lu, Yinying
肝内胆管细胞癌（ICC）是胆管癌的一种，具有很高的死亡率。肠道菌群，胆汁酸（BA）代谢和细胞因子尚未在ICC患者的特点，更好的非侵入性诊断方法ICC是必不可少的。因此，在这项研究中，我们旨在提高我们对ICC患者肠道微生物群，BA代谢和细胞因子变化的理解。我们发现，与肝细胞癌或肝硬化患者和健康个体相比，ICC的α-二聚体和β-二聚体含量最高，并且ICC患者中四个属（乳杆菌属、放线菌属、消化链球菌科和别斯卡多维亚属）的丰度增加。ICC患者的甘氨熊去氧胆酸和牛磺熊去氧胆酸（TUDCA）血浆/粪便比值明显升高。此外，与TUDCA血浆-粪便比率正相关的乳酸杆菌属和别斯卡多维亚属被组合以区分ICC与其他三种疾病。血管侵犯（VI）经常导致ICC患者预后不良。与无VI的ICC患者相比，VI患者的瘤胃球菌科丰度更高，血浆白细胞介素（IL）-4和6种结合型BA水平升高，血浆IL-6和鹅去氧胆酸水平降低。在ICC患者中观察到血浆牛磺胆酸与IL-4之间呈正相关。血浆TUDCA与伪不动杆菌属的丰度和ICC患者的生存时间呈负相关，但对肿瘤大小没有影响，如在两种小鼠肿瘤模型中所确定的。结论：在这项研究中，我们确定了一些生物标志物，包括肠道微生物群，BA和炎症细胞因子，用于诊断ICC和预测ICC患者的VI。
Intrahepatic cholangiocarcinoma (ICC), a type of bile duct cancer, has a high mortality rate. Gut microbiota, bile acid (BA) metabolism, and cytokines have not been characterized in patients with ICC, and better noninvasive diagnostic approaches for ICC are essential to be established. Therefore, in this study we aimed to improve our understanding of changes in gut microbiota, BA metabolism, and cytokines in patients with ICC. We found that the alpha-diversities and beta-diversities of ICC were highest and that the abundances of four genera (Lactobacillus, Actinomyces, Peptostreptococcaceae, and Alloscardovia) were increased in patients with ICC compared with those in patients with hepatocellular carcinoma or liver cirrhosis and in healthy individuals. The glycoursodeoxycholic acid and tauroursodeoxycholic acid (TUDCA) plasma-stool ratios were obviously increased in patients with ICC. Furthermore, the genera Lactobacillus and Alloscardovia that were positively correlated with TUDCA plasma-stool ratios were combined to discriminate ICC from the other three diseases. Vascular invasion (VI) frequently led to a poor prognosis in patients with ICC. Compared with patients with ICC without VI, patients with VI had a greater abundance of the family Ruminococcaceae, increased levels of plasma interleukin (IL)-4 and six conjugated BAs, and decreased levels of plasma IL-6 and chenodeoxycholic acid. A positive correlation between plasma taurocholic acid and IL-4 was observed in patients with ICC. Plasma TUDCA was negatively correlated with the abundance of the genus Pseudoramibacter and the survival time of patients with ICC, but had no effect on tumor size, as determined in two murine tumor models. Conclusion: In this study, we identified some biomarkers, including gut microbiota, BAs and inflammatory cytokines, for the diagnosis of ICC and prediction of VI in patients with ICC.