Liang Tingbo, Su Wei, Zhang Qi, Li Guogang, Gao Shunliang, Lou Jianying, Zhang Yun, Ma Tao, Bai Xueli
Department of Hepatobiliary and Pancreatic Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Collaborative Innovation Center for Cancer Medicine, Zhejiang University, Guangzhou, China.
Department of Hepatobiliary and Pancreatic Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
J Am Coll Surg. 2016 Mar;222(3):269-280.e10. doi: 10.1016/j.jamcollsurg.2015.12.009. Epub 2015 Dec 18.
Bile duct microenvironment plays several key roles in cholangiolithiasis occurrence. Sphincter of Oddi laxity (SOL) is associated with cholangiolithiasis, probably due to enhanced reflux of intestinal contents that changes the microenvironment. However, the microenvironment has not been investigated comprehensively.
Patients with cholangiolithiasis were consecutively recruited and their bile was collected intraoperatively for high-throughput experiments. Pyrosequencing of 16S ribosomal RNA gene was performed to characterize the microbiota in the bile. A liquid chromatography mass spectrometry-based method was used to profile bile composition. Clinical manifestation, microbiome, and bile composition were compared between patients with and without SOL.
Eighteen patients with SOL and 27 patients without SOL were finally included. Patients with SOL showed more severe inflammation. Bacteria in the bile duct were overwhelmingly aerobes and facultative anaerobes. Proteobacteria and Firmicutes were the most widespread phylotypes, especially Enterobacteriaceae. Compared with those without SOL, patients with SOL possessed more varied microbiota. In the SOL group, pathobionts, such as Bilophila and Shewanella algae had richer communities, and harmless bacteria were reduced. Metabolomics analysis showed the differences in bile composition between groups were mainly distributed in lipids and bile acids. Particularly, the increased abundance of Bilophila involved in taurine metabolism was associated with reduced contents of taurine derivatives in the bile of patients with SOL.
A bile duct microenvironment with more severe bacterial infection and stronger lithogenicity was found in patients with SOL. The findings suggest a possible mechanism of cholangiolithiasis and provide the basis for future strategies for prevention of cholangiolithiasis recurrence.
胆管微环境在胆管结石形成中起关键作用。Oddi括约肌松弛（SOL）与胆管结石相关，可能是由于肠内容物反流增加改变了微环境。然而，微环境尚未得到全面研究。
连续招募胆管结石患者，术中收集胆汁用于高通量实验。对16S核糖体RNA基因进行焦磷酸测序以鉴定胆汁中的微生物群。采用基于液相色谱质谱联用的方法分析胆汁成分。比较有和无SOL患者的临床表现、微生物组和胆汁成分。
最终纳入18例有SOL患者和27例无SOL患者。有SOL患者炎症更严重。胆管内细菌以需氧菌和兼性厌氧菌为主。变形菌门和厚壁菌门是最常见的系统发育类型，尤其是肠杆菌科。与无SOL患者相比，有SOL患者的微生物群更多样化。在SOL组中，诸如嗜胆菌属和海藻希瓦氏菌等致病共生菌群落更丰富，无害细菌减少。代谢组学分析表明，两组间胆汁成分差异主要分布在脂质和胆汁酸中。特别是，参与牛磺酸代谢的嗜胆菌属丰度增加与有SOL患者胆汁中牛磺酸衍生物含量降低有关。
在有SOL患者中发现了细菌感染更严重且致石性更强的胆管微环境。这些发现提示了胆管结石形成的可能机制，并为未来预防胆管结石复发的策略提供了依据。
