Bile acids drive chemotaxis of Clonorchis sinensis juveniles to the bile duct

Clonorchiasis is a neglected tropical disease caused by Chinese liver fluke, Clonorchis sinensis infection. C. sinensis is a biological carcinogen causing cholangiocarcinoma in humans. In the mammalian host, C. sinensis newly excysted juveniles (CsNEJs) migrate from the duodenum into the bile duct. Bile drives the chemotactic behavior of CsNEJs. Little is known about which components of bile induce the chemotaxis. We designed a chemotaxis assay panel and measured the chemotactic behavior of CsNEJs in response to bile or bile acids. The CsNEJs migrated toward 0.1–1% bile but away from 5–10% bile. The CsNEJs showed strong chemoattraction to cholic acid ≥25 mM, but chemorepulsion to lithocholic acid ≥0.25 mM. To the CsNEJs, mixture of cholic acid and lithocholic acid was chemoattractive at a ratio greater than 25:1 but chemorepulsive at one smaller than that. Regarding migration in the mammalian hosts, high concentration of lithocholic acid in the gallbladder bile may repel CsNEJs from entering it. However, bile in the hepatic bile duct has a chemoattractive strength of cholic acid but a trace amount of lithocholic acid. Collectively, our results explain why the CsNEJs migrate principally to the hepatic bile ducts, bypassing the gallbladder.华支睾吸虫病（Clonorchiasis）是由中华肝吸虫（华支睾吸虫，Clonorchis sinensis）感染引发的一种被忽视的热带病。华支睾吸虫属于生物致癌物，可诱发人类胆管癌。在哺乳动物宿主体内，华支睾吸虫脱囊后幼体（newly excysted juveniles，CsNEJs）会从十二指肠迁移至胆管。胆汁可驱动CsNEJs的趋化行为，但目前对于胆汁中哪些组分能够诱导其趋化作用仍知之甚少。本研究设计了一套趋化检测组合，检测了CsNEJs对胆汁或胆汁酸的趋化行为。结果显示，CsNEJs会向0.1%~1%浓度的胆汁发生迁移，却会避开5%~10%浓度的胆汁。CsNEJs对浓度≥25mM的胆酸表现出强烈的趋化吸引作用，而对浓度≥0.25mM的石胆酸则产生趋化排斥。当胆酸与石胆酸的混合比例大于25:1时，二者的混合物对CsNEJs具有趋化吸引活性；当比例小于该值时，则表现为趋化排斥。针对哺乳动物宿主内的迁移过程，胆囊胆汁中高浓度的石胆酸可能会排斥CsNEJs进入胆囊。然而，肝胆管内的胆汁以具有趋化吸引活性的胆酸为主要成分，且仅含痕量石胆酸。综上，本研究结果解释了为何CsNEJs会主要迁移至肝胆管，而绕过胆囊。