阴道菌群与人乳头瘤病毒感染及宫颈病变的相关性研究进展
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摘要
阴道菌群对维系女性生殖道的健康有着重要的作用。随着16SrRNA基因测序方法的发展,人们对阴道菌群的组成及结构有了更深入的认识。乳杆菌主导着健康女性的阴道环境,在保护女性泌尿生殖系统免受病原菌感染方面起着重要作用。研究者在分析了人乳头瘤病毒(HPV)感染、宫颈癌前病变、宫颈癌及细菌性阴道炎等患者的阴道菌群后,发现病变的发生与特定菌属的数量及多样性增加相关。本文对阴道菌群与HPV持续感染、宫颈病变关系的研究进展作一综述,以进一步理解病原菌与乳杆菌如何相互作用并改变阴道内环境。
Vaginal microbiota plays a crucial role in vaginal health. In recent years, our understanding of vaginal bacterial community composition and structure has been significantly broadened as a result of investigators using cultivation-independent methods based on the analysis of 16 S ribosomal RNA(rRNA) gene sequences. The healthy human vagina is dominated by lactobacilli, which play an important role in protecting the host from urogenital infections. By the analysis of the vaginal microbiome associated with human papillomavirus infection, cervical precancer and cervical cancer, researchers find that occurrences of lesions are associated with the number and the increasing diversity of specific genus bacteria. We will explain the relationship between vaginal flora and HPV infection and cervical lesions in terms of the composition of the vaginal flora and its regulatory mechanisms.
Vaginal microbiota plays a crucial role in vaginal health. In recent years, our understanding of vaginal bacterial community composition and structure has been significantly broadened as a result of investigators using cultivation-independent methods based on the analysis of 16 S ribosomal RNA(rRNA) gene sequences. The healthy human vagina is dominated by lactobacilli, which play an important role in protecting the host from urogenital infections. By the analysis of the vaginal microbiome associated with human papillomavirus infection, cervical precancer and cervical cancer, researchers find that occurrences of lesions are associated with the number and the increasing diversity of specific genus bacteria. We will explain the relationship between vaginal flora and HPV infection and cervical lesions in terms of the composition of the vaginal flora and its regulatory mechanisms.
引文
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[26]Gottschick C, Deng ZL, Vital M, et al. Treatment of biofilms in bacterial vaginosis by an amphoteric tenside pessaryclinical study and microbiota analysis[J]. Microbiome,2017, 5(1):119. doi:10.1186/s40168-017-0326-y.
[27]Bultman SJ. Emerging roles of the microbiome in cancer[J]. Carcinogenesis, 2014, 35(2):249-255. doi:10.1093/carcin/bgt392.
[28]Hedges SR, Barrientes F, Desmond RA, et al. Local and systemic cytokine levels in relation to changes in vaginal flora[J]. J Infect Dis, 2006, 193(4):556-562.
[29]Anahtar MN, Byrne EH, Doherty KE, et al. Cervicovaginal bacteria are a major modulator of host inflammatory responses in the female genital tract[J]. Immunity, 2015,42(5):965-976. doi:10.1016/j. immuni.2015.04.019.
[30]Anderson BL, Cu-Uvin S, Raker CA, et al. Subtle perturbations of genital microflora alter mucosal immunity among lowrisk pregnant women[J]. Acta Obstet Gynecol Scand, 2011,90(5):510-515. doi:10.1111/j.1600-0412.2011.01082. x.
[31]Libby EK, Pascal KE, Mordechai E, et al. Atopobium vaginae triggers an innate immune response in an in vitro model of bacterial[J]. Microbes Infect, 2008, 10(4):439-446. doi:10.1016/j. micinf.2008.01.004.
[32]Doerflinger SY, Throop AL, Herbst-Kralovetz MM. Bacteria in the vaginal microbiome alter the innate immune response and barrier properties of the human vaginal epithelia in a species-specific manner[J]. J Infect Dis, 2014, 209(12):1989-1999. doi:10.1093/infdis/jiu004.
[33]Balkwill F, Mantovani A. Inflammation and cancer:back to Virchow?[J]. Lancet, 2001, 357(9255):539-545.
[2]Vogtmann E, Hua X, Zeller G, et al. Colorectal Cancer and the Human Gut Microbiome:Reproducibility with WholeGenome Shotgun Sequencing[J]. PLoS One, 2016, 11(5):e0155362. doi:10.1371/journal. pone.0155362.
[3]Witkowska M, Smolewski P. Helicobacter pylori infection,chronic inflammation, and genomic transformations in gastric MALT lymphoma[J]. Mediators Inflamm, 2013, 2013:523170. doi:10.1155/2013/523170.
[4]Mendling W. Vaginal Microbiota[J]. Adv Exp Med Biol,2016, 902:83-93. doi:10.1007/978-3-319-31248-4_6.
[5]Martin DH. The microbiota of the vagina and its influence on women’s health and disease[J]. Am J Med Sci, 2012,343(1):2-9. doi:10.1097/MAJ.0b013e31823ea228.
[6]Boskey ER, Telsch KM, Whaley KJ, et al. Acid production by vaginal flora in vitro is consistent with the rate and extent of vaginal acidification[J]. Infect Immun, 1999, 67(10):5170-5175.
[7]Vásquez A, Jakobsson T, AhrnéS, et al. Vaginal lactobacillus flora of healthy Swedish women[J]. J Clin Microbiol,2002, 40(8):2746-2749.
[8]Ravel J, Gajer P, Abdo Z, et al. Vaginal microbiome of reproductive-age women[J]. Proc Natl Acad Sci U S A, 2011,108 Suppl 1:4680-4687. doi:10.1073/pnas.1002611107.
[9]Aroutcheva A, Gariti D, Simon M, et al. Defense factors of vaginal lactobacilli[J]. Am J Obstet Gynecol, 2001, 185(2):375-379.
[10]Motevaseli E, Shirzad M, Akrami SM, et al. Normal and tumour cervical cells respond differently to vaginal lactobacilli, independent of pH and lactate[J]. J Med Microbiol,2013, 62(Pt 7):1065-1072. doi:10.1099/jmm.0.057521-0.
[11]Sungur T, Aslim B, Karaaslan C, et al. Impact of Exopolysaccharides(EPSs)of Lactobacillus gasseri strains isolated from human vagina on cervical tumor cells(HeLa)[J]. Anaerobe, 2017, 47:137-144. doi:10.1016/j. anaerobe.2017.05.013.
[12]Nunn KL, Wang YY, Harit D, et al. Enhanced Trapping of HIV-1 by Human Cervicovaginal Mucus Is Associated with Lactobacillus crispatus-Dominant Microbiota[J]. Mbio,2015, 6(5):e01084-15. doi:10.1128/mBio.01084-15.
[13]Forman D, de Martel C, Lacey CJ, et al. Global burden of human papillomavirus and related diseases[J]. Vaccine, 2012,30 Suppl 5:F12-F23. doi:10.1016/j. vaccine.2012.07.055.
[14]Ma B, Forney LJ, Ravel J. Vaginal microbiome:rethinking health and disease[J]. Annu Rev Microbiol, 2012, 66:371-389. doi:10.1146/annurev-micro-092611-150157.
[15]Gao W, Weng J, Gao Y, et al. Comparison of the vaginal microbiota diversity of women with and without human papillomavirus infection:a cross-sectional study[J]. BMC Infect Dis, 2013, 13:271. doi:10.1186/1471-2334-13-271.
[16]潘颖,盛华芳,康玲,等.高危型人乳头状瘤病毒感染与阴道菌群的相关性研究[J].第三军医大学学报, 2016,38(13):1559-1564. doi:10.16016/j.1000-5404.201512189.
[17]Brotman RM, Shardell MD, Gajer P, et al. Interplay between the temporal dynamics of the vaginal microbiota and human papillomavirus detection[J]. J Infect Dis, 2014, 210(11):1723-1733. doi:10.1093/infdis/jiu330.
[18]Mitra A, MacIntyre DA, Lee YS, et al. Cervical intraepithelial neoplasia disease progression is associated with increased vaginal microbiome diversity[J]. Sci Rep, 2015, 5:16865. doi:10.1038/srep16865.
[19]Audirac-Chalifour A, Torres-Poveda K, Bahena-Román M, et al. Cervical Microbiome and Cytokine Profile at Various Stages of Cervical Cancer:A Pilot Study[J]. PLoS One,2016, 11(4):e0153274. doi:10.1371/journal. pone.0153274.
[20]Oh HY, Kim BS, Seo SS, et al. The association of uterine cervical microbiota with an increased risk for cervical intraepithelial neoplasia in Korea[J]. Clin Microbiol Infect, 2015,21(7):674. e1-674. e9. doi:10.1016/j. cmi.2015.02.026.
[21]Chehoud C, Stieh DJ, Bailey AG, et al. Associations of the vaginal microbiota with HIV infection, bacterial vaginosis,and demographic factors[J]. AIDS, 2017, 31(7):895-904.doi:10.1097/QAD.0000000000001421.
[22]Foxman B, Wen A, Srinivasan U, et al. Mycoplasma, bacterial vaginosis-associated bacteria BVAB3, race, and risk of preterm birth in a high-risk cohort[J]. Am J Obstet Gynecol, 2014,210(3):226. e1-226. e7. doi:10.1016/j. ajog.2013.10.003.
[23]Onderdonk AB, Delaney ML, Fichorova RN. The Human Microbiome during Bacterial Vaginosis[J]. Clin Microbiol Rev, 2016, 29(2):223-238. doi:10.1128/CMR.00075-15.
[24]Hay P. Bacterial vaginosis[J]. F1000Res, 2017, 6:1761.doi:10.12688/f1000research.11417.1.
[25]Schwebke JR, Muzny CA, Josey WE. Role of Gardnerella vaginalis in the pathogenesis of bacterial vaginosis:a conceptual model[J].J Infect Dis, 2014, 210(3):338-343. doi:10.1093/infdis/jiu089.
[26]Gottschick C, Deng ZL, Vital M, et al. Treatment of biofilms in bacterial vaginosis by an amphoteric tenside pessaryclinical study and microbiota analysis[J]. Microbiome,2017, 5(1):119. doi:10.1186/s40168-017-0326-y.
[27]Bultman SJ. Emerging roles of the microbiome in cancer[J]. Carcinogenesis, 2014, 35(2):249-255. doi:10.1093/carcin/bgt392.
[28]Hedges SR, Barrientes F, Desmond RA, et al. Local and systemic cytokine levels in relation to changes in vaginal flora[J]. J Infect Dis, 2006, 193(4):556-562.
[29]Anahtar MN, Byrne EH, Doherty KE, et al. Cervicovaginal bacteria are a major modulator of host inflammatory responses in the female genital tract[J]. Immunity, 2015,42(5):965-976. doi:10.1016/j. immuni.2015.04.019.
[30]Anderson BL, Cu-Uvin S, Raker CA, et al. Subtle perturbations of genital microflora alter mucosal immunity among lowrisk pregnant women[J]. Acta Obstet Gynecol Scand, 2011,90(5):510-515. doi:10.1111/j.1600-0412.2011.01082. x.
[31]Libby EK, Pascal KE, Mordechai E, et al. Atopobium vaginae triggers an innate immune response in an in vitro model of bacterial[J]. Microbes Infect, 2008, 10(4):439-446. doi:10.1016/j. micinf.2008.01.004.
[32]Doerflinger SY, Throop AL, Herbst-Kralovetz MM. Bacteria in the vaginal microbiome alter the innate immune response and barrier properties of the human vaginal epithelia in a species-specific manner[J]. J Infect Dis, 2014, 209(12):1989-1999. doi:10.1093/infdis/jiu004.
[33]Balkwill F, Mantovani A. Inflammation and cancer:back to Virchow?[J]. Lancet, 2001, 357(9255):539-545.