胆管结石发病机制中胆道微生物群的作用：最新研究进展

doi:10.16139/j.1007-9610.2024.06.15

摘要/Abstract

摘要：

胆管结石(BDS)的发病机制复杂，迄今尚未得到全面阐释。新近研究表明，胆道微生物群是导致BDS的重要原因。胆道微生物多样性与结石形成相关，细菌代谢产物及其自我保护机制也在结石形成中发挥关键作用。高通量测序等现代技术为深入研究提供了新视角，有望为胆道疾病防治提供新策略。本文就BDS与胆道微生物群的关系及机制的研究进展作一综述。

关键词: 胆管结石, 胆道微生物群, 高通量测序

Abstract:

The pathogenesis of bile duct stones (BDS) remains intricate and has not been fully elucidated to date. Emerging research has highlighted the biliary microbiota as a significant contributor to BDS. The diversity within the biliary microbiota correlates with stone formation, while bacterial metabolites and their self-protection mechanisms also exert pivotal roles in this process. Advanced technologies, such as high-throughput sequencing, offer fresh perspectives for in-depth exploration, and hold promise for novel strategies in the prevention and treatment of biliary tract diseases. This article comprehensively reviewed the recent advancements in research concerning the relationship and mechanisms between BDS and the biliary microbiota.

Key words: Bile duct stones(BDS), Biliary microbiota, High-throughput sequencing

中图分类号:

R657.42

王潇宁, 吴晓东, 吴硕东, 韩金岩. 胆管结石发病机制中胆道微生物群的作用：最新研究进展[J]. 外科理论与实践, 2024, 29(06): 544-548.

WANG Xiaoning, WU Xiaodong, WU Shuodong, HAN Jinyan. Role of biliary microbiota in the pathogenesis of bile duct stones: latest research progress[J]. Journal of Surgery Concepts & Practice, 2024, 29(06): 544-548.

参考文献 50

[1]	TAZUMA S. Gallstone disease: epidemiology, pathoge-nesis, and classification of biliary stones (common bile duct and intrahepatic)[J]. Best Pract Res Clin Gastroenterol, 2006, 20(6):1075-1083.
[2]	MAKI T. Pathogenesis of calcium bilirubinate gallstone: role of E. coli, beta-glucuronidase and coagulation by inorganic ions, polyelectrolytes and agitation[J]. Ann Surg, 1966, 164(1):90-100.
[3]	BEGER H G, SCHWARZ A. Review article: spectrum of biliary infections in the West and in the East[J]. HPB Surg, 1995, 8(4):215-222. doi: 10.1155/1995/74384 pmid: 18612470
[4]	TROTMAN B W, SOLOWAY R D. Pigment gallstone di-sease: summary of the National Institutes of Health-international workshop[J]. Hepatology, 1982, 2(6):879-884.
[5]	RESHETNYAK V I. Concept of the pathogenesis and treatment of cholelithiasis[J]. World J Hepatol, 2012, 4(2):18-34. doi: 10.4254/wjh.v4.i2.18 pmid: 22400083
[6]	KIM B, PARK J S, BAE J, et al. Bile microbiota in patients with pigment common bile duct stones[J]. J Korean Med Sci, 2021, 36(15):e94. doi: 10.3346/jkms.2021.36.e94 pmid: 33876584
[7]	NAGASE M, HIKASA Y, SOLOWAY R D, et al. Gallstones in Western Japan. Factors affecting the prevalence of intrahepatic gallstones[J]. Gastroenterology, 1980, 78(4):684-690. pmid: 7353754
[8]	SHODA J, TANAKA N, OSUGA T. Hepatolithiasis-epidemiology and pathogenesis update[J]. Front Biosci,2003,8:e398-e409.
[9]	WU Y, XU C J, XU S F. Advances in risk factors for recurrence of common bile duct stones[J]. Int J Med Sci, 2021, 18(4):1067-1074. doi: 10.7150/ijms.52974 pmid: 33456365
[10]	CSENDES A, BURDILES P, MALUENDA F, et al. Simultaneous bacteriologic assessment of bile from gallbladder and common bile duct in control subjects and patients with gallstones and common duct stones[J]. Arch Surg, 1996, 131(4):389-394.
[11]	PAELKE A, LENK V, SCHNEIDER V. [Initial results of bacterial contamination of the gallbladder in forensic medicine examination][J]. Beitr Gerichtl Med, 1989,47:497-502.
[12]	KOOK P H, SCHELLENBERG S, GREST P, et al. Microbiologic evaluation of gallbladder bile of healthy dogs and dogs with iatrogenic hypercortisolism: a pilot study[J]. J Vet Intern Med, 2010, 24(1):224-228. doi: 10.1111/j.1939-1676.2009.0413.x pmid: 19925578
[13]	JIMÉNEZ E, SÁNCHEZ B, FARINA A, et al. Characte-rization of the bile and gall bladder microbiota of healthy pigs[J]. Microbiologyopen, 2014, 3(6):937-949.
[14]	MOLINERO N, RUIZ L, MILANI C, et al. The human gallbladder microbiome is related to the physiological state and the biliary metabolic profile[J]. Microbiome, 2019, 7(1):100. doi: 10.1186/s40168-019-0712-8 pmid: 31272480
[15]	CETTA F. The route of infection in patients with bactibilia[J]. World J Surg, 1983, 7(4):562. pmid: 6624133
[16]	STEWART L, SMITH A L, PELLEGRINI C A, et al. Pigment gallstones form as a composite of bacterial microcolonies and pigment solids[J]. Ann Surg, 1987, 206(3):242-250. pmid: 3632090
[17]	CETTA F. The role of bacteria in pigment gallstone di-sease[J]. Ann Surg, 1991, 213(4):315-326.
[18]	CETTA F M. Bile infection documented as initial event in the pathogenesis of brown pigment biliary stones[J]. Hepatology, 1986, 6(3):482-489. pmid: 3519417
[19]	SWIDSINSKI A, LUDWIG W, PAHLIG H, et al. Molecular genetic evidence of bacterial colonization of cholesterol gallstones[J]. Gastroenterology, 1995, 108(3):860-864. pmid: 7875489
[20]	KAWAI M, IWAHASHI M, UCHIYAMA K, et al. Gram-positive cocci are associated with the formation of completely pure cholesterol stones[J]. Am J Gastroenterol, 2002, 97(1):83-88. pmid: 11808974
[21]	刘敏, 彭宇鸿, 余宇, 等. 肝内胆管结石和胆汁中细菌多样性分析[J]. 四川大学学报(自然科学版), 2014, 51(3):621-624.
	Liu M, Peng Y H, Yu Y, et al. Analysis of bacterial diversity in human hepatolithiasis and bile[J]. J Sichuan Univ(Natural Sci Edition), 2014, 51(3):621-624.
[22]	RAZAGHI M, TAJEDDIN E, GANJI L, et al. Colonization, resistance to bile, and virulence properties of Escherichia coli strains: unusual characteristics associated with biliary tract diseases[J]. Microb Pathog, 2017,111:262-268.
[23]	Human Microbiome Project Consortium. A framework for human microbiome research[J]. Nature, 2012, 486(7402):215-221.
[24]	YE F, SHEN H, LI Z, et al. Influence of the biliary system on biliary bacteria revealed by bacterial communities of the human biliary and upper digestive tracts[J]. PLoS One, 2016, 11(3):e0150519.
[25]	LIANG T, SU W, ZHANG Q, et al. Roles of sphincter of oddi laxity in bile duct microenvironment in patients with cholangiolithiasis: from the perspective of the microbiome and metabolome[J]. J Am Coll Surg, 2016, 222(3):269-280.e10.
[26]	HAN J, WU S, FAN Y, et al. Biliary microbiota in choledocholithiasis and correlation with duodenal microbiota[J]. Front Cell Infect Microbiol, 2021,11:625589.
[27]	LYU Z, YU T, ZHANG L, et al. Analysis of the relationship between bile duct and duodenal microbiota reveals that potential dysbacteriosis is the main cause of primary common bile duct stones[J]. Synth Syst Biotechnol, 2021, 6(4):414-428. doi: 10.1016/j.synbio.2021.11.002 pmid: 34901480
[28]	LEE J, PARK J S, BAE J, et al. Bile microbiome in patients with recurrent common bile duct stones and correlation with the duodenal microbiome[J]. Life (Basel), 2022, 12(10):1540.
[29]	ZHANG Q, YE M, SU W, et al. Sphincter of Oddi laxity alters bile duct microbiota and contributes to the recurrence of choledocholithiasis[J]. Ann Transl Med, 2020, 8(21):1383. doi: 10.21037/atm-20-3295 pmid: 33313128
[30]	CHOE J W, LEE J M, HYUN J J, et al. Analysis on microbial profiles & components of bile in patients with recurrent CBD stones after endoscopic CBD stone removal: a preliminary study[J]. J Clin Med, 2021, 10(15):3303.
[31]	TAN W, CHEN R, SONG J, et al. Microbiota analysis with next-generation 16S rDNA gene sequencing in recurrent common bile duct stones[J]. Ann Transl Med, 2022, 10(10):576. doi: 10.21037/atm-22-2247 pmid: 35722401
[32]	YE C, ZHOU W, ZHANG H, et al. Alterations of the bile microbiome in recurrent common bile duct stone[J]. Biomed Res Int, 2020,2020:4637560.
[33]	KOSE S H, GRICE K, ORSI W D, et al. Metagenomics of pigmented and cholesterol gallstones: the putative role of bacteria[J]. Sci Rep, 2018, 8(1):11218. doi: 10.1038/s41598-018-29571-8 pmid: 30046045
[34]	MAISONNEUVE E, GERDES K. Molecular mechanisms underlying bacterial persisters[J]. Cell, 2014, 157(3):539-548. doi: 10.1016/j.cell.2014.02.050 pmid: 24766804
[35]	BØGGILD A, SOFOS N, ANDERSEN K R, et al. The crystal structure of the intact E. coli RelBE toxin-antitoxin complex provides the structural basis for conditional cooperativity[J]. Structure, 2012, 20(10):1641-1648.
[36]	VAN DYKE A L, KEMP T J, CORBEL A F, et al. Lipopolysaccharide-pathway proteins are associated with gallbladder cancer among adults in Shanghai, China with mediation by systemic inflammation[J]. Ann Epidemiol, 2016, 26(10):704-709. doi: S1047-2797(16)30251-4 pmid: 27793274
[37]	WOHLFARTH J C, FELDMÜLLER M, SCHNELLER A, et al. L-form conversion in Gram-positive bacteria enables escape from phage infection[J]. Nat Microbiol, 2023, 8(3):387-399. doi: 10.1038/s41564-022-01317-3 pmid: 36717719
[38]	MICKIEWICZ K M, KAWAI Y, DRAGE L, et al. Possible role of L-form switching in recurrent urinary tract infection[J]. Nat Commun, 2019, 10(1):4379. doi: 10.1038/s41467-019-12359-3 pmid: 31558767
[39]	KAWAI Y, ERRINGTON J. Dissecting the roles of peptidoglycan synthetic and autolytic activities in the walled to L-form bacterial transition[J]. Front Microbiol, 2023,14:1204979.
[40]	FLEMMING H C, WINGENDER J, SZEWZYK U, et al. Biofilms: an emergent form of bacterial life[J]. Nat Rev Microbiol, 2016, 14(9):563-575.
[41]	LEUNG J W, SUNG J Y, COSTERTON J W. Bacteriological and electron microscopy examination of brown pigment stones[J]. J Clin Microbiol, 1989, 27(5):915-921. doi: 10.1128/jcm.27.5.915-921.1989 pmid: 2745700
[42]	BESTER E, WOLFAARDT G M, AZNAVEH N B, et al. Biofilms' role in planktonic cell proliferation[J]. Int J Mol Sci, 2013, 14(11):21965-21982. doi: 10.3390/ijms141121965 pmid: 24201127
[43]	HIGASHIJIMA H, ICHIMIYA H, NAKANO T, et al. Deconjugation of bilirubin accelerates coprecipitation of cholesterol, fatty acids, and mucin in human bile-in vitro study[J]. J Gastroenterol, 1996, 31(6):828-835.
[44]	LEUNG J W, LIU Y L, LEUNG P S, et al. Expression of bacterial beta-glucuronidase in human bile: an in vitro study[J]. Gastrointest Endosc, 2001, 54(3):346-350.
[45]	STEWART L, GRIFISS J M, JARVIS G A, et al. Biliary bacterial factors determine the path of gallstone formation[J]. Am J Surg, 2006, 192(5):598-603. pmid: 17071191
[46]	SWIDSINSKI A, LEE S P. The role of bacteria in gallstone pathogenesis[J]. Front Biosci,2001,6:E93-E103.
[47]	SHEN H, YE F, XIE L, et al. Metagenomic sequencing of bile from gallstone patients to identify different microbial community patterns and novel biliary bacteria[J]. Sci Rep, 2015,5:17450.
[48]	NAKANO T, YANAGISAWA J, NAKAYAMA F. Phospholipase activity in human bile[J]. Hepatology, 1988, 8(6):1560-1564. pmid: 3192169
[49]	STEWART L, PONCE R, OESTERLE A L, et al. Pigment gallstone pathogenesis: slime production by biliary bacteria is more important than beta-glucuronidase production[J]. J Gastrointest Surg, 2000, 4(5):547-553. doi: 10.1016/s1091-255x(00)80100-6 pmid: 11077333
[50]	WU X, YAO C, KONG J, et al. Molecular mechanism underlying miR‑130b‑Sp1 transcriptional regulation in LPS‑induced upregulation of MUC5AC in the bile duct epithelium[J]. Mol Med Rep, 2021, 23(2):106.