Oddi括约肌功能障碍胆道结石患者的临床与胆道菌群特征分析

Analysis of the clinical and on biliary microflora features in patients with cholelithiasis and Oddi sphincter dysfunction

背景与目的:研究显示,胆道结石(GSD)的产生与胆道微生物群的改变有关,而Oddi括约肌(SO)作为肠道与胆道之间的屏障,其功能障碍导致胆道微生物群变化情况尚不明了。因此,本研究探讨存在SO功能障碍(SOD)的GSD患者的临床特征以及胆管内微生物菌群与SO功能正常GSD患者菌群差异。方法:前瞻性招募2019—2021年间青海省人民医院行急诊手术治疗的胆囊结石伴胆总管结石患者14例,根据术中所测SO压力值,其中7例存在SOD(SOD组),7例SO功能正常(SO正常组)。收集所有患者术前及术后3个月胆汁标本,对所收集的样本进行16S rRNA基因提取及扩增子测序,用QIIME 2微生物组生物信息学平台分析16S rRNA基因扩增子测序数据。结果:SOD组患者术前白细胞计数明显高于SO正常组患者(P<0.05),而两组患者间其他相关化验指标及一般情况均无明显差异(均P>0.05)。所有病例中均发现了不同的胆汁微生物群落;丰度等级曲线分析结果表明,SOD组术后标本的菌群丰度最高,随后依次为SO正常组术后样本、SOD组术前样本、SO正常组术前样本;两组患者的4组胆汁样本中的菌群属分布各不相同,相对于SO功能正常的GSD患者,有SOD的GSD患者的菌群种类更加集中在埃希氏菌属、梭状芽孢杆菌属和肠球菌属。结论:存在SOD的GSD患者的炎症负荷更高、胆道菌群的丰度显著增加,较SO功能正常的GSD患者,出现更多与结石相关的菌群,可能更易引起胆道感染与结石复发。

Background and Aims:Studies have indicated that gallstone disease(GSD)is related to the alterations of the bile duct microbiome.However,the bile duct microbiome changes caused by abnormal function of the sphincter of Oddi(SO)that serves as the barrier between the intestinal tract and biliary tract are not fully known.Therefore,this study investigated the differences in clinical features and bile tract microbiotas between GSD patients with concomitant SO dysfunction(SOD)and GSD patients with normal SO function.Methods:Fourteen patients with cholecystolithiasis and choledocholithiasis undergoing an emergency operation from 2019 to 2021 in Qinghai Provincial People’s Hospital were prospectively recruited.Of the patients,7 cases presented with SOD(SOD group),and 7 cases had normal SO function(normal SO group)according to the value of the SO pressure determined during operation.All patients’bile specimens were obtained before and three months after the operation.The 16S rRNA genes were extracted from the collected samples,and amplicon sequencing was performed.Then,the amplicon sequencing data of the 16S rRNA genes were analyzed using QIIME 2 microbiome bioinformatics platform.Results:The preoperative white blood count in patients of the SOD group was significantly higher than that of the normal SO group(P<0.05).At the same time,the parameters of other laboratory tests and the general conditions showed no significant difference between the two groups of patients(all P>0.05).Different bile duct microbiotas were observed in all patients.The microbial abundance was highest in the postoperative samples from the SOD group,followed by postoperative samples from the normal SO group,preoperative samples from the SOD group,and preoperative samples from the normal SO group,successively.The distributions of species of the microbiota of the four groups of bile samples from the two groups were different from each other,and the bacterial communities involved in GSD patients with SOD were predominantly of Escherichia,Clostridium,and Enterococcus versus GSD patients with normal SO function.Conclusion:GSD patients with SOD have a higher inflammatory burden and significantly increased microbial abundance.They present increased species of bacteria associated with cholelithiasis compared with GSD patients with normal SO function,which may more likely cause biliary tract infection and recurrent stones.