The Therapeutic Potential of Lactobacillus crispatus for Chronic Endometritis: A Comprehensive Clinical Trial and Experimental Investigation.
Lactobacillus crispatus
Chronic endometritis
Inflammatory factor
Sterility
Journal
Probiotics and antimicrobial proteins
ISSN: 1867-1314
Titre abrégé: Probiotics Antimicrob Proteins
Pays: United States
ID NLM: 101484100
Informations de publication
Date de publication:
22 Aug 2024
22 Aug 2024
Historique:
accepted:
15
08
2024
medline:
22
8
2024
pubmed:
22
8
2024
entrez:
22
8
2024
Statut:
aheadofprint
Résumé
Chronic endometritis (CE) is common in patients with infertility, and it is challenging to treat with antibiotics as bacteria often acquire resistance to the antibiotics, which leads to frequent recurrence of the condition. Probiotics, especially Lactobacillus species, are known for their usefulness in treating reproductive infections. This study evaluated Lactobacillus crispatus chen 01 (L. crispatus chen 01) isolated from healthy women who were 22-30 years old and married with children. In vitro experiments showed that L. crispatus chen 01 inhibited pathogens and reduced inflammation in CE mice by downregulating inflammatory proteins (TLR, MyD88, and p65/p-p65; L + Abx vs M, P < 0.01), improving histopathological features, and inhibiting bacterial growth. It also regulated endometrial processes, such as enhancing embryo implantation (BMP2 and Wnt4, L + Abx vs M, P < 0.01) via the Wnt/β-catenin pathway, leading to increased pregnancy rates (L + Abx vs M, 100% vs 0%) in mice. In clinical trials, L. crispatus chen 01 improved progesterone levels (P = 0.0038), pregnancy rates (C vs Abx + L. c, 76.19% vs 87.18%), and pathological changes in CE patients. The findings from this study identify the administration of L. crispatus chen 01 as a promising intervention for CE that could improve pregnancy rates.
Identifiants
pubmed: 39172215
doi: 10.1007/s12602-024-10349-6
pii: 10.1007/s12602-024-10349-6
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Nanchang Science and Technology Support Plan Project
ID : 2022146
Organisme : Natural Science Foundation of Jiangxi Province
ID : 20192ACBL20038
Organisme : Traditional Chinese Medicine of Science and Technology Program Fund of Jiangxi Province
ID : 2020Z001
Organisme : Major Project of Science and Technology Technology Program of Jiangxi Province
ID : 20152ACG70022
Organisme : Double Thousand Plan of Jiangxi Province to T.-T.C
ID : High-End Talents project of Scientific and Technological Innovation
Informations de copyright
© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
Références
Kimura F, Takebayashi A, Ishida M, Nakamura A, Kitazawa J, Morimune A, Hirata K, Takahashi A, Tsuji S, Takashima A et al (2019) Review: chronic endometritis and its effect on reproduction. J Obstet Gynaecol Res 45:951–960
pubmed: 30843321
doi: 10.1111/jog.13937
Li Y, Yu S, Huang C, Lian R, Chen C, Liu S, Li L, Diao L, Markert UR, Zeng Y (2020) Evaluation of peripheral and uterine immune status of chronic endometritis in patients with recurrent reproductive failure. Fertil Steril 113:187-196.e1
pubmed: 31718829
doi: 10.1016/j.fertnstert.2019.09.001
Chen P, Chen P, Guo Y, Fang C, Li T (2021) Interaction between chronic endometritis caused endometrial microbiota disorder and endometrial immune environment change in recurrent implantation failure. Front Immunol 12:748447
pubmed: 34671363
pmcid: 8521098
doi: 10.3389/fimmu.2021.748447
Pirtea P, Cicinelli E, De Nola R, de Ziegler D, Ayoubi JM (2020) Endometrial causes of recurrent pregnancy losses: endometriosis, adenomyosis, and chronic endometritis. Fertil Steril 115:546–560
doi: 10.1016/j.fertnstert.2020.12.010
Cao W, Fu X, Zhou J, Qi Q, Ye F, Li L, Wang L (2024) The effect of the female genital tract and gut microbiome on reproductive dysfunction. Biosci Trends 17:458–474
pubmed: 38104979
doi: 10.5582/bst.2023.01133
Li J, Li X, Ding J, Zhao J, Chen J, Guan F, Deng H, Zhou M, Han Y, Xiao Z et al (2023) Analysis of pregnancy outcomes in patients with recurrent implantation failure complicated with chronic endometritis. Front Cell Dev Biol 11:1088586
pubmed: 36861040
pmcid: 9969095
doi: 10.3389/fcell.2023.1088586
Duan H, Li X, Hao Y, Shi J, Cai H (2022) Risk of spontaneous abortion after antibiotic therapy for chronic endometritis before in vitro fertilization and intracytoplasmic sperm injection stimulation. Fertil Steril 118:337–346
pubmed: 35691723
doi: 10.1016/j.fertnstert.2022.04.026
Molina NM, Sola-Leyva A, Saez-Lara MJ, Plaza-Diaz J, Tubić-Pavlović A, Romero B, Clavero A, Mozas-Moreno J, Fontes J, Altmäe S (2020) New opportunities for endometrial health by modifying uterine microbial composition: present or future? Biomolecules 10:593
pubmed: 32290428
pmcid: 7226034
doi: 10.3390/biom10040593
Mancabelli L, Tarracchini C, Milani C, Lugli GA, Fontana F, Turroni F, van Sinderen D, Ventura M (2021) Vaginotypes of the human vaginal microbiome. Environ Microbiol 23:1780–1792
pubmed: 33615652
doi: 10.1111/1462-2920.15441
Holm JB, France MT, Gajer P, Ma B, Brotman RM, Shardell M, Forney L, Ravel J (2024) Correction: integrating compositional and functional content to describe vaginal microbiomes in health and disease. Microbiome 12(1):21
pubmed: 38321533
pmcid: 10845452
doi: 10.1186/s40168-024-01765-5
Saraf VS, Sheikh SA, Ahmad A, Gillevet PM, Bokhari H, Javed S (2021) Vaginal microbiome: normalcy vs dysbiosis. Arch Microbiol 203:3793–3802
pubmed: 34120200
doi: 10.1007/s00203-021-02414-3
Kong Y, Liu Z, Xiao Q, Wu F, Hu L, Deng X, Chen T (2022) Protective effects of engineered Lactobacillus crispatus on intrauterine adhesions in mice via delivering CXCL12. Front Immunol 13:905876
pubmed: 35734171
pmcid: 9207254
doi: 10.3389/fimmu.2022.905876
Happel AU, Kullin B, Gamieldien H, Wentzel N, Zauchenberger CZ, Jaspan HB, Dabee S, Barnabas SL, Jaumdally SZ, Dietrich J et al (2020) Exploring potential of vaginal Lactobacillus isolates from South African women for enhancing treatment for bacterial vaginosis. PLoS Pathog 16:e1008559
pubmed: 32497109
pmcid: 7271994
doi: 10.1371/journal.ppat.1008559
You S, Zhu Y, Li H, He F, Liu S, Yang X, Wang L, Zeng H, Dai J, Hu L (2023) Recombinant humanized collagen remodels endometrial immune microenvironment of chronic endometritis through macrophage immunomodulation. Regen Biomater 10:rbad033
pubmed: 37122820
pmcid: 10147517
doi: 10.1093/rb/rbad033
Zheng Z, Guo Y, Zheng Y, Wu H (2024) miR-92b ameliorates lipoteichoic acid induced endometritis by suppressing Wnt/β-catenin pathway activation. Theriogenology 214:307–313
pubmed: 37956579
doi: 10.1016/j.theriogenology.2023.11.003
Ng HHM, Lee RY, Goh S, Tay ISY, Lim X, Lee B, Chew V, Li H, Tan B, Lim S et al (2020) Immunohistochemical scoring of CD38 in the tumor microenvironment predicts responsiveness to anti-PD-1/PD-L1 immunotherapy in hepatocellular carcinoma. J Immunother Cancer 8:e000987
pubmed: 32847986
pmcid: 7451957
doi: 10.1136/jitc-2020-000987
Abramov VM, Kosarev IV, Priputnevich TV, Machulin AV, Khlebnikov VS, Pchelintsev SY, Vasilenko RN, Sakulin VK, Suzina NE, Chikileva IO et al (2020) S-layer protein 2 of Lactobacillus crispatus 2029, its structural and immunomodulatory characteristics and roles in protective potential of the whole bacteria against foodborne pathogens. Int J Biol Macromol 150:400–412
pubmed: 32045605
doi: 10.1016/j.ijbiomac.2020.02.065
Fakharian F, Sadeghi A, Pouresmaeili F, Soleimani N, Yadegar A (2023) Immunomodulatory effects of live and pasteurized Lactobacillus crispatus strain RIGLD-1 on Helicobacter pylori-triggered inflammation in gastric epithelial cells in vitro. Mol Biol Rep 50:6795–6805
pubmed: 37392285
doi: 10.1007/s11033-023-08596-x
Huang Q, Yang Y, Yuan L, Zhao Y, Qin A (2023) Oil-based contrast for hysterosalpingography-regulated Th1/Th2-type cytokines and alleviated inflammation in rats with LPS-induced chronic endometritis. J Obstet Gynaecol Res 49:243–252
pubmed: 36281209
doi: 10.1111/jog.15451
France M, Alizadeh M, Brown S, Ma B, Ravel J (2022) Towards a deeper understanding of the vaginal microbiota. Nat Microbiol 7:367–378
pubmed: 35246662
pmcid: 8910585
doi: 10.1038/s41564-022-01083-2
Bhurke A, Kannan A, Neff A, Ma Q, Laws MJ, Taylor RN, Bagchi MK, Bagchi IC (2020) A hypoxia-induced Rab pathway regulates embryo implantation by controlled trafficking of secretory granules. Proc Natl Acad Sci U S A 117:14532–14542
pubmed: 32513733
pmcid: 7321991
doi: 10.1073/pnas.2000810117
Zhai J, Ma L, Chang Z, Yu T (2022) Increased expression of prokineticin 2 and its receptor in endometrium of recurrent implantation failure patients decreased the expression of MMP9 important for decidualization. Reprod Biol Endocrinol 20:76
pubmed: 35501804
pmcid: 9059424
doi: 10.1186/s12958-022-00947-w
Esencan E, Beroukhim G, Seifer DB (2022) Age-related changes in Folliculogenesis and potential modifiers to improve fertility outcomes - a narrative review. Reprod Biol Endocrinol 20:156
pubmed: 36397149
pmcid: 9670479
doi: 10.1186/s12958-022-01033-x
Wang CY, Tsai PY, Chen TY, Tsai HL, Kuo PL, Su MT (2019) Elevated miR-200a and miR-141 inhibit endocrine gland-derived vascular endothelial growth factor expression and ciliogenesis in preeclampsia. J Physiol 597:3069–3083
pubmed: 31026335
doi: 10.1113/JP277704
Morales-Hernández FV, Bautista-Bautista G, Acuña-González RJ, Vázquez-Cárdenas P, López-Canales JS, Lozano-Cuenca J, Osorio-Caballero M, Flores-Herrera H (2022) Differential proMMP-2 and proMMP-9 secretion in human pre-implantation embryos at day 5 of development. Acta Biochim Pol 69:683–689
pubmed: 36112527
Di Pierro F, Sinatra F, Cester M, Da Ros L, Pistolato M, Da Parè V, Fabbro L, Maccari D, Dotto S, Sossai S et al (2023) Effect of L. crispatus M247 administration on pregnancy outcomes in women undergoing IVF: a controlled, retrospective, observational, and open-label study. Microorganisms 11:2796
pubmed: 38004807
pmcid: 10673025
doi: 10.3390/microorganisms11112796
Guan W, Dong S, Wang Z, Jiao J, Wang X (2023) Impact of a Lactobacillus dominant cervical microbiome, based on 16S-FAST profiling, on the reproductive outcomes of IVF patients. Front Cell Infect Microbiol 13:1059339
pubmed: 37305412
pmcid: 10250658
doi: 10.3389/fcimb.2023.1059339
Kadogami D, Kimura F, Hanada T, Tsuji S, Nakaoka Y, Murakami T, Morimoto Y (2023) Impact of Lactobacillus in the uterine microbiota on in vitro fertilization outcomes. J Reprod Immunol 160:104138
pubmed: 37717556
doi: 10.1016/j.jri.2023.104138
Zhang Q, Pan Y, Ji J, Xu Y, Zhang Q, Qin L (2021) Roles and action mechanisms of WNT4 in cell differentiation and human diseases: a review. Cell Death Discov 7:287
pubmed: 34642299
pmcid: 8511224
doi: 10.1038/s41420-021-00668-w
Au J, Requena DF, Rishik H, Kallol S, Tekkatte C, Farah OA, Kittle R, Meads M, Wakeland A, Soncin F (2022) Role of autocrine bone morphogenetic protein signaling in trophoblast stem cells†. Biol Reprod 106:540–550
pubmed: 34791028
doi: 10.1093/biolre/ioab213
Salker MS, Singh Y, Durairaj RRP, Yan J, Alauddin M, Zeng N, Steel JH, Zhang S, Nautiyal J, Webster Z et al (2018) LEFTY2 inhibits endometrial receptivity by downregulating Orai1 expression and store-operated Ca
pubmed: 29230527
doi: 10.1007/s00109-017-1610-9
França MM, Mendonca BB (2022) Genetics of ovarian insufficiency and defects of folliculogenesis. Best Pract Res Clin Endocrinol Metab 36:101594
pubmed: 34794894
doi: 10.1016/j.beem.2021.101594
Sader F, Roy S (2021) Tgf-β superfamily and limb regeneration: Tgf-β to start and Bmp to end. Dev Dyn 251:973–987
pubmed: 34096672
doi: 10.1002/dvdy.379
Reddi AH (1994) Bone and cartilage differentiation. Curr Opin Genet Dev 4:737–744
pubmed: 7849513
doi: 10.1016/0959-437X(94)90141-O
Shafiei S, Farah O, Dufort D (2021) Maternal Cripto is required for proper uterine decidualization and peri-implantation uterine remodeling. Biol Reprod 104:1045–1057
pubmed: 33590845
pmcid: 8111237
doi: 10.1093/biolre/ioab020
Lee KY, Jeong JW, Wang J, Ma L, Martin JF, Tsai SY, Lydon JP, DeMayo FJ (2007) Bmp2 is critical for the murine uterine decidual response. Mol Cell Biol 27:5468–5478
pubmed: 17515606
pmcid: 1952078
doi: 10.1128/MCB.00342-07
Pitzer LM, Moroney MR, Nokoff NJ, Sikora MJ (2021) WNT4 balances development vs disease in gynecologic tissues and women’s health. Endocrinology 162:bqab093
pubmed: 33963381
pmcid: 8197283
doi: 10.1210/endocr/bqab093
Vainio S, Heikkilä M, Kispert A, Chin N, McMahon AP (1999) Female development in mammals is regulated by Wnt-4 signalling. Nature 397:405–409
pubmed: 9989404
doi: 10.1038/17068
Biason-Lauber A, Konrad D (2008) WNT4 and sex development. Sex Dev 2:210–218
pubmed: 18987495
doi: 10.1159/000152037
Pellegrino M, Maiorino R, Schonauer S (2010) WNT4 signaling in female gonadal development. Endocr Metab Immune Disord Drug Targets 10:168–174
pubmed: 20350288
doi: 10.2174/187153010791213074
Tanaka SE, Sakuraba Y, Kitaya K, Ishikawa T (2020) Differential vaginal microbiota profiling in lactic-acid-producing bacteria between infertile women with and without chronic endometritis. Diagnostics (Basel) 12:878
doi: 10.3390/diagnostics12040878
Lüll K, Saare M, Peters M, Kakhiani E, Zhdanova A, Salumets A, Boyarsky K, Org E (2022) Differences in microbial profile of endometrial fluid and tissue samples in women with in vitro fertilization failure are driven by Lactobacillus abundance. Acta Obstet Gynecol Scand 101:212–220
pubmed: 35092013
pmcid: 9564573
doi: 10.1111/aogs.14297
Liang J, Li M, Zhang L, Yang Y, Jin X, Zhang Q, Lv T, Huang Z, Liao Q, Tong X (2023) Analysis of the microbiota composition in the genital tract of infertile patients with chronic endometritis or endometrial polyps. Front Cell Infect Microbiol 13:1125640
pubmed: 37284497
pmcid: 10240353
doi: 10.3389/fcimb.2023.1125640
Odawara K, Akino R, Sekizawa A, Sakamoto M, Yuriko S, Tanaka K, Mikashima M, Suzuki M, Odawara Y (2021) Examination of clinical factors affecting intrauterine microbiota. Reprod Fertil 2:1–6
pubmed: 35128428
pmcid: 8812463
doi: 10.1530/RAF-20-0030
Iwami N, Kawamata M, Ozawa N, Yamamoto T, Watanabe E, Mizuuchi M, Moriwaka O, Kamiya H (2023) Therapeutic intervention based on gene sequencing analysis of microbial 16S ribosomal RNA of the intrauterine microbiome improves pregnancy outcomes in IVF patients: a prospective cohort study. J Assist Reprod Genet 40:125–135
pubmed: 36534230
doi: 10.1007/s10815-022-02688-6