Biliary microbiota and mucin 4 impact the calcification of cholesterol gallstones
Biliary microbiota and mucin 4 impact the calcification of cholesterol gallstones
复制标题
胆道微生物群和粘蛋白 4 影响胆固醇胆结石的钙化
DOI：
10.1016/j.hbpd.2020.12.002
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发表时间：
2021-02-18
影响因子：
3.3
通讯作者：
Xu, Guo-Qiang
中科院分区：
文献类型：
--
作者：
Hu, Feng-Ling;Chen, Hong-Tan;Xu, Guo-Qiang
背景资料：胆固醇结石占胆结石的80%以上，胆结石形成的发病机制涉及遗传和环境因素。然而，各种密度的胆固醇结石的演变数据是有限的。本研究旨在探讨微生物群和粘蛋白在胆石症患者钙化胆固醇结石形成中的作用。方法：取胆石症患者的胆囊组织和胆汁标本，根据结石密度分为等密度组和钙化组。检测胆囊组织中微生物群的相对丰度。采用免疫组化和酶联免疫吸附试验检测胆囊组织和胆汁中MUC 1、MUC 2、MUC 3a、MUC 3b、MUC 4、MUC 5ac和MUC 5 b的表达水平。结果：23例胆囊结石患者均行胆囊镜下活检，胆囊镜下活检标本均行胆囊镜下活检，胆囊镜下活检标本均行胆囊镜下活检，胆囊镜下活检标本均行胆囊镜下活检。等密度组的结石密度明显低于钙化组（34.20 ± 1.50对109.40 ± 3.84 HU，P < 0.0001）。与等密度组相比，钙化组在胆囊组织的底部、体部和颈部显示出更高丰度的革兰氏阳性菌。胆囊组织上皮细胞MUC 1、MUC 2、MUC 3a、MUC 3b、MUC 5ac和MUC 5 b的浓度在两组间无差异，而MUC 4的浓度在钙化组明显高于等密度组（15.49 +/- 0.69 vs. 10.23 +/- 0.54 ng/mL，P < 0.05），体内（14.54 +/- 0.94 vs. 11.87 +/- 0.85 ng/mL，P < 0.05）以及胆囊组织颈部（14.77 +/- 1.04 vs. 10.85 +/- 0.72 ng/mL，P < 0.05）。结论：胆囊结石患者胆汁微生物群、粘蛋白与结石钙化之间存在潜在的临床相关性。革兰氏阳性菌群和MUC 4可能与胆固醇结石的钙化呈正相关。(C)2020中国浙江大学医学院附属第一医院。Elsevier B. V.出版，保留所有权利。
Background: Cholesterol gallstones account for over 80% of gallstones, and the pathogenesis of gallstone formation involves genetic and environmental factors. However, data on the evolution of cholesterol gallstones with various densities are limited. This study aimed to determine the roles of microbiota and mucins on the formation of calcified cholesterol gallstones in patients with cholelithiasis.Methods: Paired gallbladder tissues and bile specimens were obtained from cholelithiasis patients who were categorized into the isodense group and calcified group according to the density of gallstones. The relative abundance of microbiota in gallbladder tissues was detected. Immunohistochemistry and enzyme-linked immunosorbent assay were performed to detect the expression levels of MUC1, MUC2, MUC3a, MUC3b, MUC4, MUC5ac and MUC5b in gallbladder tissues and bile. The correlation of microbiota abundance with MUC4 expression was evaluated by linear regression.Results: A total of 23 patients with gallbladder stones were included. The density of gallstones in the isodense group was significantly lower than that of the calcified group (34.20 +/- 1.50 vs. 109.40 +/- 3.84 HU, P < 0.0001). Compared to the isodense group, the calcified group showed a higher abundance of gram-positive bacteria at the fundus, in the body and neck of gallbladder tissues. The concentrations of MUC1, MUC2, MUC3a, MUC3b, MUC5ac and MUC5b in the epithelial cells of gallbladder tissues showed no difference between the two groups, while the concentrations of MUC4 were significantly higher in the calcified group than that in the isodense group at the fundus (15.49 +/- 0.69 vs. 10.23 +/- 0.54 ng/mL, P < 0.05), in the body (14.54 +/- 0.94 vs. 11.87 +/- 0.85 ng/mL, P < 0.05) as well as in the neck (14.77 +/- 1.04 vs. 10.85 +/- 0.72 ng/mL, P < 0.05) of gallbladder tissues. Moreover, the abundance of bacteria was positively correlated with the expression of MUC4 (r = 0.569, P < 0.05) in the calcified group.Conclusions: This study showed the potential clinical relevance among biliary microbiota, mucins and calcified gallstones in patients with gallstones. Gram-positive microbiota and MUC4 may be positively associated with the calcification of cholesterol gallstones. (C) 2020 First Affiliated Hospital, Zhejiang University School of Medicine in China. Published by Elsevier B.V. All rights reserved.