Journal of Shandong University (Health Sciences) ›› 2025, Vol. 63 ›› Issue (5): 120-126.doi: 10.6040/j.issn.1671-7554.0.2024.0976

• Review • Previous Articles    

Connection between reproductive tract microbes and the development of endometriosis

ZHANG Shuqi, JIANG Yanjiao, YIN Dan   

  1. The Second School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang, China
  • Published:2025-05-07

PDF (PC)

104

Abstract: Microorganisms in the human body play a crucial role in human health. Maintaining the ecological balance of the internal microbial flora in the human body to achieve a balanced immune system is conducive to maintaining health. Dysbiosis of this microbial community has been linked to the onset of various diseases, including endometriosis. In cases of endometriosis, such dysbiosis may incite chronic inflammation, thereby fostering an environment conducive to its progression. This review specifically analyzed how dysbiosis in this region influences the pathogenesis of endometriosis, aiming to provide references by elucidating these underlying mechanisms.

Key words: Endometriosis, Reproductive tract microorganism, Ecological imbalance, Inflammatory mediators, Immune status, Hormone levels

CLC Number: 

  • R711.71
[1] Bulun SE, Yilmaz BD, Sison C, et al. Endometriosis[J]. Endocr Rev, 2019, 40(4): 1048-1079.
[2] Zondervan KT, Becker CM, Missmer SA. Endometriosis[J]. N Engl J Med, 2020, 382(13): 1244-1256.
[3] Taylor HS, Kotlyar AM, Flores VA. Endometriosis is a chronic systemic disease: clinical challenges and novel innovations[J]. Lancet, 2021, 397(10276): 839-852.
[4] Ruff WE, Greiling TM, Kriegel MA. Host-microbiota interactions in immune-mediated diseases[J]. Nat Rev Microbiol, 2020, 18(9): 521-538.
[5] Zondervan KT, Becker CM, Koga K, et al. Endometriosis[J]. Nat Rev Dis Primers, 2018, 4(1): 9. doi:10.1038/s41572-018-0008-5
[6] Lin WC, Chang CY, Hsu YA, et al. Increased risk of endometriosis in patients with lower genital tract infection: a nationwide cohort study[J]. Medicine, 2016, 95(10): e2773. doi:10.1097/MD.0000000000002773
[7] Khan S, Imran A, Malik A, et al. Bacterial imbalance and gut pathologies: association and contribution of E. coli in inflammatory bowel disease[J]. Crit Rev Clin Lab Sci, 2019, 56(1): 1-17.
[8] Lu WT, He F, Lin Z, et al. Dysbiosis of the endometrial microbiota and its association with inflammatory cytokines in endometrial cancer[J]. Int J Cancer, 2021, 148(7): 1708-1716.
[9] Zhu J, Chen YC, Chen H, et al. Comparison of microbial abundance and diversity in uterine and peritoneal fluid in infertile patients with or without endometriosis[J]. BMC Womens Health, 2024, 24(1): 148.
[10] Chen C, Song XL, Wei WX, 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
[11] 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.
[12] Sobstyl A, Chaupnik A, Mertowska P, et al. How do microorganisms influence the development of endometrio-sis? participation of genital, intestinal and oral micro-biota in metabolic regulation and immunopathogenesis of endometriosis[J]. Int J Mol Sci, 2023, 24(13): 10920. doi:10.3390/ijms241310920
[13] Uzuner C, Mak J, El-Assaad F, et al. The bidirectional relationship between endometriosis and microbiome[J]. Front Endocrinol, 2023, 14: 1110824. doi:10.3389/fendo.2023.1110824
[14] Walther-António MRS, Chen J, Multinu F, et al. Potential contribution of the uterine microbiome in the development of endometrial cancer[J]. Genome Med, 2016, 8(1): 122. doi:10.1186/s13073-016-0368-y
[15] Huang LJ, Liu BD, Liu ZH, et al. Gut microbiota exceeds cervical microbiota for early diagnosis of endometriosis[J]. Front Cell Infect Microbiol, 2021, 11: 788836. doi:10.3389/fcimb.2021.788836
[16] Wei WX, Zhang XW, Tang HR, 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
[17] Chang CY, Chiang A, Lai M, 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
[18] Medina-Bastidas D, Camacho-Arroyo I, García-Gómez E. Current findings in endometrial microbiome: impact on uterine diseases[J]. Reproduction, 2022, 163(5): R81-R96.
[19] Moosa Y, Kwon D, de Oliveira T, et al. Determinants of vaginal microbiota composition[J]. Front Cell Infect Microbiol, 2020, 10: 467. doi:10.3389/fcimb.2020.00467
[20] Cocomazzi G, De Stefani S, Del Pup L, et al. The impact of the female genital microbiota on the outcome of assisted reproduction treatments[J]. Microorganisms, 2023, 11(6): 1443. doi:10.3390/microorganisms11061443
[21] Anahtar MN, Gootenberg DB, Mitchell CM, et al. Cervicovaginal microbiota and reproductive health: the virtue of simplicity[J]. Cell Host Microbe, 2018, 23(2): 159-168.
[22] Baker JM, Chase DM, Herbst-Kralovetz MM. Uterine microbiota: residents, tourists, or invaders?[J]. Front Immunol, 2018, 9: 208. doi:10.3389/fimmu.2018.00208
[23] Kroon SJ, Ravel J, Huston WM. Cervicovaginal microbiota, womens health, and reproductive outcomes[J]. Fertil Steril, 2018, 110(3): 327-336.
[24] Chao XP, Liu Y, Fan QB, et al. The role of the vaginal microbiome in distinguishing female chronic pelvic pain caused by endometriosis/adenomyosis[J]. Ann Transl Med, 2021, 9(9): 771. doi:10.21037/atm-20-4586
[25] Hernandes C, Silveira P, Rodrigues Sereia AF, et al. Microbiome profile of deep endometriosis patients: comparison of vaginal fluid, endometrium and lesion[J]. Diagnostics, 2020, 10(3): 163. doi:10.3390/diagnostics10030163
[26] Ata B, Yildiz S, Turkgeldi E, et al. The endobiota study: comparison of vaginal, cervical and gut microbiota between women with stage 3/4 endometriosis and healthy controls[J]. Sci Rep, 2019, 9(1): 2204. doi:10.1038/s41598-019-39700-6
[27] Yang Q, Wang YN, Cai H, et al. Translocation of vaginal and cervical low-abundance non-Lactobacillus bac-teria notably associate with endometriosis: a pilot study[J]. Microb Pathog, 2023, 183: 106309. doi:10.1016/j.micpath.2023.106309
[28] Chang CY, Chiang AJ, 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
[29] Khan KN, Fujishita A, Masumoto H, et al. Molecular detection of intrauterine microbial colonization in women with endometriosis[J]. Eur J Obstet Gynecol Reprod Biol, 2016, 199: 69-75. doi:10.1016/j.ejogrb.2016.01.040
[30] Akiyama K, Nishioka K, Khan KN, et al. Molecular detection of microbial colonization in cervical mucus of women with and without endometriosis[J]. Am J Reprod Immunol, 2019, 82(2): e13147. doi:10.1111/aji.13147
[31] 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.
[32] 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.
[33] Plesniarski A, Siddik AB, Su RC. The microbiome as a key regulator of female genital tract barrier function[J]. Front Cell Infect Microbiol, 2021, 11: 790627. doi:10.3389/fcimb.2021.790627
[34] Krautkramer KA, Fan J, Bäckhed F. Gut microbial metabolites as multi-Kingdom intermediates[J]. Nat Rev Microbiol, 2021, 19(2): 77-94.
[35] Fan Y, Pedersen O. Gut microbiota in human metabolic health and disease[J]. Nat Rev Microbiol, 2021, 19(1): 55-71.
[36] Liao C, Rolling T, Djukovic A, et al. Oral bacteria relative abundance in faeces increases due to gut microbiota depletion and is linked with patient outcomes[J]. Nat Microbiol, 2024, 9(6): 1555-1565.
[37] 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
[38] Houshdaran S, Nezhat CR, Vo KC, et al. Aberrant endometrial DNA methylome and associated gene expression in women with endometriosis[J]. Biol Reprod, 2016, 95(5): 93. doi:10.1095/biolreprod.116.140434
[39] Symons LK, Miller JE, Kay VR, et al. The immunopathophysiology of endometriosis[J]. Trends Mol Med, 2018, 24(9): 748-762.
[40] Patel BG, Lenk EE, Lebovic DI, et al. Pathogenesis of endometriosis: interaction between endocrine and infla-mmatory pathways[J]. Best Pract Res Clin Obstet Gynaecol, 2018, 50: 50-60. doi:10.1016/j.bpobgyn.2018.01.006
[41] Izumi G, Koga K, Takamura M, et al. Involvement of immune cells in the pathogenesis of endometriosis[J]. J Obstet Gynaecol Res, 2018, 44(2): 191-198.
[42] Guo B, Chen JH, Zhang JH, et al. Pattern-recognition receptors in endometriosis: a narrative review[J]. Front Immunol, 2023, 14: 1161606. doi:10.3389/fimmu.2023.1161606
[43] Muraoka A, Suzuki M, Hamaguchi T, et al. Fusobacterium infection facilitates the development of endometriosis through the phenotypic transition of endometrial fibroblasts[J]. Sci Transl Med, 2023, 15(700): eadd1531. doi:10.1126/scitranslmed.add1531
[44] Ilhan ZE, Łaniewski P, Tonachio A, et al. Members of Prevotella genus distinctively modulate innate immune and barrier functions in a human three-dimensional endometrial epithelial cell model[J]. J Infect Dis, 2020, 222(12): 2082-2092.
[45] Łaniewski P, Gomez A, Hire G, et al. Human three-dimensional endometrial epithelial cell model to study host interactions with vaginal bacteria and Neisseria gono-rrhoeae[J]. Infect Immun, 2017, 85(3): e01049-16. doi:10.1128/IAI.01049-16
[46] de Azevedo BC, Mansur F, Podgaec S. A systematic review of toll-like receptors in endometriosis[J]. Arch Gynecol Obstet, 2021, 304(2): 309-316.
[47] Bullon P, Navarro JM. Inflammasome as a key pathog-enic mechanism in endometriosis[J]. Curr Drug Targets, 2017, 18(9): 997-1002.
[48] Maddern J, Grundy L, Castro J, et al. Pain in endometriosis[J]. Front Cell Neurosci, 2020, 14: 590823. doi:10.3389/fncel.2020.590823
[49] Kolanska K, Alijotas-Reig J, Cohen J, et al. Endometrio-sis with infertility: a comprehensive review on the role of immune deregulation and immunomodulation therapy[J]. Am J Reprod Immunol, 2021, 85(3): e13384. doi:10.1111/aji.13384
[50] Vallvé-Juanico J, Houshdaran S, Giudice LC. The endometrial immune environment of women with endometriosis[J]. Hum Reprod Update, 2019, 25(5): 564-591.
[51] Saraswat L, Ayansina DT, Cooper KG, et al. Pregnancy outcomes in women with endometriosis: a national record linkage study[J]. BJOG, 2017, 124(3): 444-452.
[52] Gobek-Grenda A, Olejnik A. In vitro modeling of endometriosis and endometriotic microenvironment- Challenges and recent advances[J]. Cell Signal, 2022, 97: 110375. doi:10.1016/j.cellsig.2022.110375
[53] Crispim PCA, Jammal MP, Murta EFC, et al. Endometriosis: what is the influence of immune cells?[J]. Immunol Invest, 2021, 50(4): 372-388.
[54] Le N, Cregger M, Fazleabas A, et al. Effects of endometriosis on immunity and mucosal microbial community dynamics in female olive baboons[J]. Sci Rep, 2022, 12(1): 1590. doi:10.1038/s41598-022-05499-y
[55] Baker JM, Al-Nakkash L, Herbst-Kralovetz MM. Estrogen-gut microbiome axis: physiological and clinical implications[J]. Maturitas, 2017, 103: 45-53. doi:10.1016/j.maturitas.2017.06.025
[56] Ladanyi C, Boyd S, Sticco P, et al. Postmenopausal endometriosis, where are we now?[J]. Curr Opin Obstet Gynecol, 2019, 31(4): 267-278.
[57] Chantalat E, Valera MC, Vaysse C, et al. Estrogen receptors and endometriosis[J]. Int J Mol Sci, 2020, 21(8): 2815. doi:10.3390/ijms21082815
[58] Galvankar M, Singh N, Modi D. Estrogen is essential but not sufficient to induce endometriosis[J]. J Biosci, 2017, 42(2): 251-263.
[59] Muhleisen AL, Herbst-Kralovetz MM. Menopause and the vaginal microbiome[J]. Maturitas, 2016, 91: 42-50. doi:10.1016/j.maturitas.2016.05.015
[60] Muzny CA, Łaniewski P, Schwebke JR, et al. Host-vaginal microbiota interactions in the pathogenesis of bacterial vaginosis[J]. Curr Opin Infect Dis, 2020, 33(1): 59-65.
[61] Cregger MA, Lenz K, Leary E, et al. Reproductive microbiomes: using the microbiome as a novel diagnostic tool for endometriosis[J]. Reproductive Immunol Open Acc, 2017, 2(3). doi:10.21767/2476-1974.100036
[62] Wang Y, Nicholes K, Shih IM. The origin and pathogenesis of endometriosis[J]. Annu Rev Pathol, 2020, 15: 71-95. doi:10.1146/annurev-pathmechdis-012419-032654
[63] Molina NM, Sola-Leyva A, Saez-Lara MJ, et al. New opportunities for endometrial health by modifying uterine microbial composition: present or future?[J]. Biomo-lecules, 2020, 10(4): 593. doi:10.3390/biom10040593
[64] Morotti M, Vincent K, Becker CM. Mechanisms of pain in endometriosis[J]. Eur J Obstet Gynecol Reprod Biol, 2017, 209: 8-13. doi:10.1016/j.ejogrb.2016.07.497
[65] Tampaki EC, Tampakis A, Kontzoglou K, et al. Commentary: somatic stem cells and their dysfunction in endometriosis[J]. Front Surg, 2017, 4: 37. doi:10.3389/fsurg.2017.00037
[66] Ervin SM, Li H, Lim L, et al. Gut microbial β-glucuronidases reactivate estrogens as components of the estrobolome that reactivate estrogens[J]. J Biol Chem, 2019, 294(49): 18586-18599.
[67] Perrotta AR, Borrelli GM, Martins CO, et al. The vaginal microbiome as a tool to predict rASRM stage of disease in endometriosis: a pilot study[J]. Reprod Sci, 2020, 27(4): 1064-1073.
[68] 林珊珊, 李哲, 杨柳, 等. 机器学习在微生物生态领域的应用文献计量分析[J]. 微生物学通报, 2024, 51(9): 3673-3689. LIN Shanshan, LI Zhe, YANG Liu, et al. Bibliometric analysis of machine learning in microbial ecology[J]. Microbiology China, 2024, 51(9): 3673-3689.
[1] ZHANG Lixia, TIAN Yizheng, LYU Shangge, ZHANG Yanan, YAN Lei. Effects of GnRH-a pretreatment on the pregnancy outcomes of frozen embryo transplantation in patients with endometriosis [J]. Journal of Shandong University (Health Sciences), 2023, 61(10): 63-68.
[2] YAN Lei, YUE Caixin, LIU Yichun. Fertility preservation in patients with endometriosis [J]. Journal of Shandong University (Health Sciences), 2022, 60(9): 31-34.
[3] LENG Jinhua, SHI Jinghua. Clinical manifestations of adenomyosis [J]. Journal of Shandong University (Health Sciences), 2022, 60(7): 1-5.
[4] CHEN Zhongshao, CHU Ran, LI Mingbao, ZHANG Xiangning. MRKH syndrome-related abdominal scar endometriosis after inguinal uterine hernia repair: a case report and literature review [J]. Journal of Shandong University (Health Sciences), 2022, 60(5): 114-117.
[5] LIN Xueyan, ZHANG Cancan, TIAN Minle, TIAN Yongjie. Expression and significance of poly(ADP-ribose) polymerase-1 in endometriosis [J]. Journal of Shandong University (Health Sciences), 2022, 60(2): 27-31.
[6] SHAN Jing, WANG Xiaoqiu, LI Dajin. Molecular mechanisms of NK cells involved in endometriosis and its associated infertility [J]. Journal of Shandong University (Health Sciences), 2021, 59(8): 8-13.
[7] LIANG Yanchun, YE Haihua, LU Limei, DAI Yujing, CHENG Qianyi, CHOI Unleng, ZENG Hanqiu, CHEN Xinghuan, WANG Xing, WEI Yajing, YANG Ruyu. Effects of chronic endometritis on the pregnancy outcomes of patients with endometriosis-associated infertility [J]. Journal of Shandong University (Health Sciences), 2021, 59(3): 55-59.
[8] XUE Yuan, LIN Xueyan, XU Ge, TIAN Yongjie. Expression of hypoxia-inducible factor-1α in the serum of patients with endometriosis and its effect on epithelial mesenchymal transition of eutopic endometrial stromal cells [J]. Journal of Shandong University (Health Sciences), 2021, 59(2): 41-47.
[9] Endometriosis and Chronic Pelvic Pain Training Center of Shandong Medical Doctor AssociationWANG Guoyun, WANG Kai, YUAN Ming, CHEN Zijiang. Multidimensional management system for endometriosis (The Program for Shandong Province) [J]. Journal of Shandong University (Health Sciences), 2021, 59(10): 1-17.
[10] LENG Jinhua, SHI Jinghua. Long-term management strategy of endometriosis [J]. Journal of Shandong University (Health Sciences), 2019, 57(6): 1-5.
[11] YAO Shuzhong, LIANG Yanchun, WEI Yajing. Surgical treatment of endometriosis [J]. Journal of Shandong University (Health Sciences), 2019, 57(6): 6-15.
[12] ZHANG Xinmei, QIAN Honglang. Clinical manifestations of endometriosis [J]. Journal of Shandong University (Health Sciences), 2019, 57(6): 16-22.
[13] LIU Chongdong, LOU Tong, DONG Jing. Malignant transformation of endometriosis [J]. Journal of Shandong University (Health Sciences), 2019, 57(6): 27-32.
[14] HUANG Wei, LIU Dong. Fertility improvement strategies for endometriosis associated infertility [J]. Journal of Shandong University (Health Sciences), 2019, 57(6): 23-26.
[15] WANG Guoyun, YUAN Ming, JI Miaomiao. Research advances in the pathogenesis of endometriosis [J]. Journal of Shandong University (Health Sciences), 2019, 57(6): 33-39.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
No Suggested Reading articles found!
Copyright 2018 © Editorial office of Journal of Shandong University (Health Sciences)
Supported by Beijing Magtech Co.Ltd