Comprehensive Liver Cancer Center, The Fifth Medical Center of PLA General Hospital, Beijing, China.
Hepatobiliary Surgery Center, The Fifth Medical Center of PLA General Hospital, Beijing, China.
Hepatology. 2020 Mar;71(3):893-906. doi: 10.1002/hep.30852. Epub 2019 Aug 19.
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 α-diversities and β-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.
肝内胆管癌（ICC）是一种胆管癌，死亡率很高。尚未对 ICC 患者的肠道微生物群、胆汁酸（BA）代谢和细胞因子进行描述，因此需要建立更好的非侵入性 ICC 诊断方法。因此，在这项研究中，我们旨在提高对 ICC 患者肠道微生物群、BA 代谢和细胞因子变化的认识。我们发现，ICC 的α多样性和β多样性最高，与肝细胞癌或肝硬化患者以及健康个体相比，ICC 患者的四种属（乳杆菌属、放线菌属、消化链球菌科和 Alloscardovia 属）丰度增加。甘氨鹅脱氧胆酸和牛磺鹅脱氧胆酸（TUDCA）的血浆-粪便比值在 ICC 患者中明显升高。此外，与 TUDCA 血浆-粪便比值呈正相关的属乳杆菌属和 Alloscardovia 属被组合用于区分 ICC 与其他三种疾病。血管侵犯（VI）常导致 ICC 患者预后不良。与无 VI 的 ICC 患者相比，有 VI 的患者的 Ruminococcaceae 家族丰度更高，血浆白细胞介素（IL）-4 和六种结合型 BA 水平升高，而血浆 IL-6 和鹅脱氧胆酸水平降低。在 ICC 患者中观察到血浆牛磺胆酸与 IL-4 之间存在正相关。血浆 TUDCA 与拟杆菌属的丰度和 ICC 患者的生存时间呈负相关，但对肿瘤大小没有影响，这在两种小鼠肿瘤模型中得到了证实。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 ICC 的诊断和预测 ICC 患者的 VI。
