宫腔微生物与女性生殖健康疾病的关系

doi:10.12280/gjszjk.20220111

摘要/Abstract

摘要：

近年,应用二代测序和微生物组学技术证实,宫腔内存在独特的微生物菌群定植,宫腔微生物的变化不仅与生理因素有关,更与女性生殖健康疾病密切相关。然而,对宫腔核心微生物组成以及宿主-微生物间的关系仍未阐明。宫腔内微生物菌群紊乱与慢性子宫内膜炎症、胚胎反复植入失败、子宫内膜异位症和宫腔粘连等生殖系统疾病的发生、发展有关,但对于宫腔微生态失调的评估方案及纠正菌群紊乱的最佳治疗方案仍未达成共识。研究发现,经阴道给予益生菌/益生元可在一定程度上辅助治疗宫腔内微生物紊乱,改善妊娠结局。综述宫腔微生物及其与女性生殖健康状态的关系。

关键词: 宫腔, 微生物群, 子宫内膜炎, 子宫内膜异位症, 组织黏连, 妊娠结局, 胚胎植入, 治疗

Abstract:

The microbiota colonizing in the uterine cavity has been demonstrated by next-generation sequencing and microbiome technology in recent years. The changes of uterine microbiota are connected not only with physiological factors, but also with female reproductive healthy diseases. However, the core composition of uterine microbiota and the relationship between the host and the microbiota still remain unknown. The disorder of uterine microbiota could be related to the pathogenesis and pathophysiology of chronic endometritis, recurrent implantation failure, endometriosis and intrauterine adhesion, etc. However, there is not a consensus on the unified protocol to assess the dysbiosis of uterine microbiota and the optimal treatment protocol to adjust above dysbiosis. To some extent, probiotics or prebiotics using in vagina can assist to treat the dysbiosis of uterine microbiota and to improve the pregnancy outcome. In this review, we discussed the uterine microbiota and its relationship with female reproductive health.

Key words: Uterine, Microbiota, Endometritis, Endometriosis, Tissue adhesion, Pregnancy outcome, Embryo implantation, Therapy

张明玮, 漆倩荣, 谢青贞. 宫腔微生物与女性生殖健康疾病的关系[J]. 国际生殖健康/计划生育, 2022, 41(3): 214-218.

ZHANG Ming-wei, QI Qian-rong, XIE Qing-zhen. Relationship of Uterine Microbiota and Female Reproductive Healthy Diseases[J]. Journal of International Reproductive Health/Family Planning, 2022, 41(3): 214-218.

参考文献 43

[1]	Zhao X, Zhao Q, Zhu X, et al. Study on the correlation among dysbacteriosi, simbalance of cytokine and the formation of intrauterine adhesion[J]. Ann Transl Med, 2020, 8(4):52. doi: 10.21037/atm.2019.11.124. doi: 10.21037/atm.2019.11.124 URL
[2]	Chen C, Song X, Wei W, et al. The microbiota continuum along the female reproductive tract and its relation to uterine-related diseases[J]. Nat Commun, 2017, 8(1):875.doi: 10.1038/s41467-017-00901-0. doi: 10.1038/s41467-017-00901-0 pmid: 29042534
[3]	Wang J, Li Z, Ma X, et al. Translocation of vaginal microbiota is involved in impairment and protection of uterine health[J]. Nat Commun, 2021, 12(1):4191. doi: 10.1038/s41467-021-24516-8. doi: 10.1038/s41467-021-24516-8 URL
[4]	González A, Vázquez-Baeza Y, Knight R. SnapShot: The Human Microbiome[J]. Cell, 2014, 158(3):690. doi: 10.1016/j.cell.2014. 07.019. doi: 10.1016/j.cell.2014.07.019 pmid: 25083877
[5]	Moreno I, Garcia-Grau I, Bau D, et al. The first glimpse of the endometrial microbiota in early pregnancy[J]. Am J Obstet Gynecol, 2020, 222(4):296-305. doi: 10.1016/j.ajog.2020.01.031. doi: 10.1016/j.ajog.2020.01.031 URL
[6]	Kitaya K, Nagai Y, Arai W, et al. Characterization of Microbiota in Endometrial Fluid and Vaginal Secretions in Infertile Women with Repeated Implantation Failure[J]. Mediators Inflamm, 2019, 2019:4893437. doi: 10.1155/2019/4893437. doi: 10.1155/2019/4893437
[7]	Leoni C, Ceci O, Manzari C, et al. Human Endometrial Microbiota at Term of Normal Pregnancies[J]. Genes, 2019, 10(12):971. doi: 10.3390/genes10120971. doi: 10.3390/genes10120971 URL
[8]	Winters AD, Romero R, Gervasi MT, et al. Does the endometrial cavity have a molecular microbial signature?[J]. Sci Rep, 2019, 9(1):9905. doi: 10.1038/s41598-019-46173-0. doi: 10.1038/s41598-019-46173-0 pmid: 31289304
[9]	Xiong Y, Chen Q, Chen C, et al. Impact of oral antibiotic treatment for chronic endometritis on pregnancy outcomes in the following frozen-thawed embryo transfer cycles of infertile women: a cohort study of 640 embryo transfer cycles[J]. Fertil Steril, 2021, 116(2):413-421. doi: 10.1016/j.fertnstert.2021.03.036. doi: 10.1016/j.fertnstert.2021.03.036 URL
[10]	Kyono K, Hashimoto T, Kikuchi S, et al. A pilot study and case reports on endometrial microbiota and pregnancy outcome: An analysis using 16S rRNA gene sequencing among IVF patients,and trial therapeutic intervention for dysbiotic endometrium[J]. Rep Med Biol, 2019, 18(1):72-82. doi: 10.1002/rmb2.12250. doi: 10.1002/rmb2.12250
[11]	Koedooder R, Mackens S, Budding A, et al. Identification and evaluation of the microbiome in the female and male reproductive tracts[J]. Hum Reprod Update, 2018, 25(3):298-325. doi: 10.1093/humupd/dmy048. doi: 10.1093/humupd/dmy048 URL
[12]	Wee BA, Thomas M, Sweeney EL, et al. A retrospective pilot study to determine whether the reproductive tract microbiota differs between women with a history of infertility and fertile women[J]. Aust N Z J Obstet Gynaecol, 2018, 58(3):341-348. doi: 10.1111/ajo.12754. doi: 10.1111/ajo.12754 URL
[13]	Kimura F, Takebayashi A, Ishida M, et al. Review: Chronic endometritis and its effect on reproduction[J]. J Obstet Gynaecol Res, 2019, 45(5):951-960. doi: 10.1111/jog.13937. doi: 10.1111/jog.13937 URL
[14]	Liu Y, Ko EY, Wong KK, et al. Endometrial microbiota in infertile women with and without chronic endometritis as diagnosed using a quantitative and reference range-based method[J]. Fertil Steril, 2019, 112(4):707-717. doi: 10.1016/j.fertnstert.2019.05.015. doi: 10.1016/j.fertnstert.2019.05.015 URL
[15]	Lozano FM, Bernabeu A, Lledo B, et al. Characterization of the vaginal and endometrial microbiome in patients with chronic endometritis[J]. Eur J Obstet Gynecol Reprod Biol, 2021, 263:25-32. doi: 10.1016/j.ejogrb.2021.05.045. doi: 10.1016/j.ejogrb.2021.05.045 pmid: 34144490
[16]	Li Y, Yu S, Huang C, et al. Evaluation of peripheral and uterine immune status of chronic endometritis in patients with recurrent reproductive failure[J]. Fertil Steril, 2020, 113(1):187-196. doi: 10.1016/j.fertnstert.2019.09.001. doi: 10.1016/j.fertnstert.2019.09.001 URL
[17]	Chen P, Chen P, Guo Y, et al. Interaction Between Chronic Endometritis Caused Endometrial Microbiota Disorder and Endometrial Immune Environment Change in Recurrent Implantation Failure[J]. Front Immunol, 2021, 12:748447. doi: 10.3389/fimmu.2021.748447. doi: 10.3389/fimmu.2021.748447 URL
[18]	Haggerty CL, Totten PA, Tang G, et al. Identification of novel microbes associated with pelvic inflammatory disease and infertility[J]. Sex Transm Infect, 2016, 92(6):441-446. doi: 10.1136/sextrans-2015-052285. doi: 10.1136/sextrans-2015-052285 URL
[19]	Fu M, Zhang X, Liang Y, et al. Alterations in Vaginal Microbiota and Associated Metabolome in Women with Recurrent Implantation Failure[J]. mBio, 2020, 11(3):e03242-19. doi: 10.1128/mBio.03242-19. doi: 10.1128/mBio.03242-19
[20]	Hashimoto T, Kyono K. Does dysbiotic endometrium affect blastocyst implantation in IVF patients?[J]. J Assist Reprod Genet, 2019, 36(12):2471-2479. doi: 10.1007/s10815-019-01630-7. doi: 10.1007/s10815-019-01630-7 URL
[21]	Franasiak JM, Werner MD, Juneau CR, et al. Endometrial microbiome at the time of embryo transfer: next-generation sequencing of the 16S ribosomal subunit[J]. J Assist Reprod Genet, 2016, 33(1):129-136. doi: 10.1007/s10815-015-0614-z. doi: 10.1007/s10815-015-0614-z URL
[22]	Jiang I, Yong PJ, Allaire C, et al. Intricate Connections between the Microbiota and Endometriosis[J]. Int J Mol Sci, 2021, 22(11):5644. doi: 10.3390/ijms22115644. doi: 10.3390/ijms22115644 URL
[23]	Leonardi M, Hicks C, El-Assaad F, et al. Endometriosis and the microbiome: a systematic review[J]. BJOG, 2020, 127(2):239-249. doi: 10.1111/1471-0528.15916. doi: 10.1111/1471-0528.15916 URL
[24]	Vargas E, Aghajanova L, Gemzell-Danielsson K, et al. Cross-disorder analysis of endometriosis and its comorbid diseases reveals shared genes and molecular pathways and proposes putative biomarkers of endometriosis[J]. Reprod Biomed Online, 2020, 40(2):305-318. doi: 10.1016/j.rbmo.2019.11.003. doi: S1472-6483(19)30802-8 pmid: 31926826
[25]	Signorile PG, Viceconte R, Baldi A. Novel dietary supplement association reduces symptoms in endometriosis patients[J]. J Cell Physiol, 2018, 233(8):5920-5925. doi: 10.1002/jcp.26401. doi: 10.1002/jcp.26401 pmid: 29243819
[26]	Khan KN, Fujishita A, Hiraki K, et al. Bacterial contamination hypothesis: a new concept in endometriosis[J]. Reprod Med Biol, 2018, 17(2):125-133. doi: 10.1002/rmb2.12083. doi: 10.1002/rmb2.12083 URL
[27]	Wei W, Zhang X, Tang H, et al. Microbiota composition and distribution along the female reproductive tract of women with endometriosis[J]. Ann Clin Microbiol Antimicrob, 2020, 19(1):15. doi: 10.1186/s12941-020-00356-0. doi: 10.1186/s12941-020-00356-0 URL
[28]	Hernandes C, Silveira P, Rodrigues Sereia AF, et al. Microbiome Profile of Deep Endometriosis Patients: Comparison of Vaginal Fluid,Endometrium and Lesion[J]. Diagnostics (Basel), 2020, 10(3):163. doi: 10.3390/diagnostics10030163. doi: 10.3390/diagnostics10030163
[29]	Chang CY, Chiang A, Lai MT, et al. A More Diverse Cervical Microbiome Associates with Better Clinical Outcomes in Patients with Endometriosis: A Pilot Study[J]. Biomedicines, 2022, 10(1):174. doi: 10.3390/biomedicines10010174. doi: 10.3390/biomedicines10010174 URL
[30]	Chen S, Gu Z, Zhang W, et al. Microbiome of the lower genital tract in Chinese women with endometriosis by 16s-rRNA sequencing technique: a pilot study[J]. Ann Transl Med, 2020, 8(21):1440. doi: 10.21037/atm-20-1309. doi: 10.21037/atm-20-1309 URL
[31]	中华医学会妇产科学分会. 宫腔粘连临床诊疗中国专家共识[J]. 中华妇产科杂志, 2015, 50(12):881-887. doi: 10.3760/cma.j.issn.0529-567x.2015.12.001. doi: 10.3760/cma.j.issn.0529-567x.2015.12.001
[32]	Liu Z, Kong Y, Gao Y, et al. Revealing the interaction between intrauterine adhesion and vaginal microbiota using high-throughput sequencing[J]. Mol Med Rep, 2019, 19(5):4167-4174. doi: 10.3892/mmr.2019.10092. doi: 10.3892/mmr.2019.10092
[33]	Qiu T, Liu L, Zhou H, et al. Analysis of endometrial microbiota in intrauterine adhesion by high-throughput sequencing[J]. Ann Transl Med, 2021, 9(3):195. doi: 10.21037/atm-20-2813. doi: 10.21037/atm-20-2813 URL
[34]	Liu L, Yang H, Guo Y, et al. The impact of chronic endometritis on endometrial fibrosis and reproductive prognosis in patients with moderate and severe intrauterine adhesions: a prospective cohort study[J]. Fertil Steril, 2019, 111(5):1002-1010. doi: 10.1016/j.fertnstert.2019.01.006. doi: 10.1016/j.fertnstert.2019.01.006 URL
[35]	Kyono K, Hashimoto T, Nagai Y, et al. Analysis of endometrial microbiota by 16S ribosomal RNA gene sequencing among infertile patients: a single-center pilot study[J]. Reprod Med Biol, 2018, 17(3):297-306. doi: 10.1002/rmb2.12105. doi: 10.1002/rmb2.12105 URL
[36]	Riganelli L, Iebba V, Piccioni M, et al. Structural Variations of Vaginal and Endometrial Microbiota: Hints on Female Infertility[J]. Front Cell Infect Microbiol, 2020, 10:350. doi: 10.3389/fcimb.2020.00350. doi: 10.3389/fcimb.2020.00350 URL
[37]	Moreno I, Codoñer FM, Vilella F, et al. Evidence that the endometrial microbiota has an effect on implantation success or failure[J]. Am J Obstet Gynecol, 2016, 215(6):684-703. doi: 10.1016/j.ajog.2016.09.075. doi: 10.1016/j.ajog.2016.09.075 URL
[38]	Chen W, Wei K, He X, et al. Identification of Uterine Microbiota in Infertile Women Receiving in vitro Fertilization With and Without Chronic Endometritis[J]. Front Cell Dev Biol, 2021, 9:693267. doi: 10.3389/fcell.2021.693267. doi: 10.3389/fcell.2021.693267 URL
[39]	Song D, He Y, Wang Y, et al. Impact of antibiotic therapy on the rate of negative test results for chronic endometritis: a prospective randomized control trial[J]. Fertil Steril, 2021, 115(6):1549-1556. doi: 10.1016/j.fertnstert.2020.12.019. doi: 10.1016/j.fertnstert.2020.12.019 URL
[40]	Cicinelli E, Resta L, Loizzi V, et al. Antibiotic therapy versus no treatment for chronic endometritis: a case-control study[J]. Fertil Sterility, 2021, 115(6):1541-1548. doi: 10.1016/j.fertnstert.2021.01.018. doi: 10.1016/j.fertnstert.2021.01.018 URL
[41]	Xu F, Shen X, Sun C, et al. The Effect of Mitomycin C on Reducing Endometrial Fibrosis for Intrauterine Adhesion[J]. Med Sci Monit, 2020, 26:e920670. doi: 10.12659/MSM.920670. doi: 10.12659/MSM.920670
[42]	Lopez-Moreno A, Aguilera M. Probiotics Dietary Supplementation for Modulating Endocrine and Fertility Microbiota Dysbiosis[J]. Nutrients, 2020, 12(3):757. doi: 10.3390/nu12030757. doi: 10.3390/nu12030757 URL
[43]	Dizzell S, Nazli A, Reid G, et al. Protective Effect of Probiotic Bacteria and Estrogen in Preventing HIV-1-Mediated Impairment of Epithelial Barrier Integrity in Female Genital Tract[J]. Cells, 2019, 8(10):1120. doi: 10.3390/cells8101120. doi: 10.3390/cells8101120 URL