{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T17:31:50Z","timestamp":1787592710449,"version":"build-2736575974"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,5,18]],"date-time":"2023-05-18T00:00:00Z","timestamp":1684368000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100002012","name":"Chemotherapy Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100002012","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"\n Background<\/jats:title>\n \n The vaginal microbiota can be altered by uropathogenic bacteria associated with recurrent cystitis (RC), and the vaginal administration of\n Lactobacillus<\/jats:italic>\n have suggested certain effects to prevent RC. The relationship between vaginal microbiota and the development of RC has not been elucidated. We aimed to clarify the etiology of RC from vaginal microbiota and importance of vaginal\n Lactobacillus<\/jats:italic>\n .\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Vaginal samples obtained from 39 postmenopausal women were classified into four groups: healthy controls; uncomplicated cystitis; RC; and prevention (prevented RC by\n Lactobacillus crispatus<\/jats:italic>\n -containing vaginal suppositories). Principal coordinate analysis and beta-diversity analysis was used to assess 16S rRNA gene sequencing data from the vaginal microbiome.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Cluster analysis divided the vaginal bacterial communities among 129 vaginal samples into three clusters (A, B, and C). Fourteen of 14 (100%) samples from the RC group and 51 of 53 (96%) samples from the prevention group were in clusters B and C, while 29 of 38 (76%) samples from the healthy group and 14 of 24 (58%) samples from the uncomplicated cystitis group were in cluster A. The principal coordinate analysis showed that plots in the uncomplicated cystitis group were similar to the healthy group, indicating a large separation between the RC group and the uncomplicated cystitis group. On beta-diversity analysis, there were significant differences between the healthy group and the uncomplicated cystitis group (\n p<\/jats:italic>\n \u2009=\u20090.045), and between the RC group and the uncomplicated cystitis group or the healthy group (\n p<\/jats:italic>\n \u2009=\u20090.001,\n p<\/jats:italic>\n \u2009=\u20090.001, respectively). There were no significant differences between the RC group and the prevention group (\n p<\/jats:italic>\n \u2009=\u20090.446). The top six taxa were as follows:\n Prevotella, Lactobacillus, Streptococcus, Enterobacteriaceae, Anaerococcus,<\/jats:italic>\n and\n Bifidobacterium<\/jats:italic>\n . Among patients with RC,\n Lactobacillus<\/jats:italic>\n was undetectable before administration of suppositories, while the median relative abundance of\n Lactobacillus<\/jats:italic>\n was 19% during administration of suppositories (\n p<\/jats:italic>\n \u2009=\u20090.0211), reducing the average cystitis episodes per year (6.3 vs. 2.4,\n p<\/jats:italic>\n \u2009=\u20090.0015).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n The vaginal microbiota of postmenopausal women with RC is differed from healthy controls and uncomplicated cystitis in terms of lack of\n Lactobacillus<\/jats:italic>\n and relatively dominant of\n Enterobacteriaceae<\/jats:italic>\n . Vaginal administration of\n Lactobacillus<\/jats:italic>\n -containing suppositories can prevent RC by stabilizing vaginal dysbiosis and causing a loss of pathogenic bacteria virulence.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fmicb.2023.1187479","type":"journal-article","created":{"date-parts":[[2023,5,18]],"date-time":"2023-05-18T01:51:25Z","timestamp":1684374685000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":16,"title":["Etiology of recurrent cystitis in postmenopausal women based on vaginal microbiota and the role of Lactobacillus vaginal suppository"],"prefix":"10.3389","volume":"14","author":[{"given":"Takanori","family":"Sekito","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichiro","family":"Wada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayano","family":"Ishii","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takehiro","family":"Iwata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takehiro","family":"Matsubara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuta","family":"Tomida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masami","family":"Watanabe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Motoo","family":"Araki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takuya","family":"Sadahira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,5,18]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"282","DOI":"10.1097\/JU.0000000000000296","article-title":"Recurrent uncomplicated urinary tract infections in women: AUA\/CUA\/SUFU guideline","volume":"202","author":"Anger","year":"2019","journal-title":"J. Urol."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1155\/S1064744901000060","article-title":"Antimicrobial protein produced by vaginal Lactobacillus acidophilus that inhibits Gardnerella vaginalis","volume":"9","author":"Aroutcheva","year":"2001","journal-title":"Infect. Dis. Obstet. Gynecol."},{"key":"ref3","doi-asserted-by":"publisher","first-page":"2900","DOI":"10.3389\/fmicb.2019.02900","article-title":"Diverse expression of antimicrobial activities against bacterial vaginosis and urinary tract infection pathogens by Cervicovaginal microbiota strains of Lactobacillus gasseri and Lactobacillus crispatus","volume":"10","author":"Atassi","year":"2019","journal-title":"Front. Microbiol."},{"key":"ref4","doi-asserted-by":"publisher","first-page":"36","DOI":"10.3390\/pathogens5020036","article-title":"Non-antibiotic prophylaxis for urinary tract infections","volume":"5","author":"Beerepoot","year":"2016","journal-title":"Pathogens"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"924","DOI":"10.1038\/mi.2016.112","article-title":"MV140, a sublingual polyvalent bacterial preparation to treat recurrent urinary tract infections, licenses human dendritic cells for generating Th1, Th17, and IL-10 responses via Syk and MyD88","volume":"10","author":"Benito-Villalvilla","year":"2017","journal-title":"Mucosal Immunol."},{"key":"ref6","volume-title":"Guidelines on urological infections EAU guidelines","author":"Bonkat","year":"2019"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"1985","DOI":"10.1128\/IAI.66.5.1985-1989.1998","article-title":"Adherence of human vaginal lactobacilli to vaginal epithelial cells and interaction with uropathogens","volume":"66","author":"Boris","year":"1998","journal-title":"Infect. Immun."},{"key":"ref8","doi-asserted-by":"publisher","first-page":"27","DOI":"10.3390\/pathogens5010027","article-title":"Cytoprotective effect of Lactobacillus crispatus CTV-05 against Uropathogenic E. coli","volume":"5","author":"Butler","year":"2016","journal-title":"Pathogens."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1186\/s12934-020-01464-4","article-title":"Vaginal microbiota and the potential of Lactobacillus derivatives in maintaining vaginal health","volume":"19","author":"Chee","year":"2020","journal-title":"Microb. Cell Factories"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1097\/SPV.0000000000000749","article-title":"Vaginal estrogen for the prevention of recurrent urinary tract infection in postmenopausal women: a randomized clinical trial","volume":"27","author":"Ferrante","year":"2021","journal-title":"Female Pelvic Med. Reconstr. Surg."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"193","DOI":"10.3389\/fmicb.2019.00193","article-title":"Comparison of the vaginal microbiomes of premenopausal and postmenopausal women","volume":"10","author":"Gliniewicz","year":"2019","journal-title":"Front. Microbiol."},{"key":"ref12","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1016\/j.idc.2013.10.002","article-title":"Management of urinary tract infections from multidrug-resistant organisms","volume":"28","author":"Gupta","year":"2014","journal-title":"Infect. Dis. Clin. N. Am."},{"key":"ref13","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1007\/978-1-4939-8728-3_8","article-title":"16S rRNA gene analysis with QIIME2","volume":"1849","author":"Hall","year":"2018","journal-title":"Methods Mol. Biol."},{"key":"ref14","doi-asserted-by":"publisher","first-page":"2698","DOI":"10.1038\/s41598-022-06646-1","article-title":"Urine and vaginal microbiota compositions of postmenopausal and premenopausal women differ regardless of recurrent urinary tract infection and renal transplant status","volume":"12","author":"Hugenholtz","year":"2022","journal-title":"Sci. Rep."},{"key":"ref15","doi-asserted-by":"publisher","first-page":"242","DOI":"10.1080\/13697137.2018.1551871","article-title":"The etiology and management of recurrent urinary tract infections in postmenopausal women","volume":"22","author":"Jung","year":"2019","journal-title":"Climacteric"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"452","DOI":"10.1038\/bmt.2012.244","article-title":"Investigation of the freely available easy-to-use software \u201cEZR\u201d for medical statistics","volume":"48","author":"Kanda","year":"2013","journal-title":"Bone Marrow Transplant."},{"key":"ref17","doi-asserted-by":"publisher","first-page":"2050","DOI":"10.1016\/j.juro.2006.07.014","article-title":"Adherence of Lactobacillus crispatus to vaginal epithelial cells from women with or without a history of recurrent urinary tract infection","volume":"176","author":"Kwok","year":"2006","journal-title":"J. Urol."},{"key":"ref18","doi-asserted-by":"publisher","first-page":"507024","DOI":"10.3389\/fpubh.2020.507024","article-title":"Community state types of vaginal microbiota and four types of abnormal vaginal microbiota in pregnant Korean women","volume":"8","author":"Lee","year":"2020","journal-title":"Front. Public Health"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"Doc02","DOI":"10.3205\/id000046","article-title":"Roles of the vagina and the vaginal microbiota in urinary tract infection: evidence from clinical correlations and experimental models","volume":"8","author":"Lewis","year":"2020","journal-title":"GMS Infect Dis."},{"key":"ref20","doi-asserted-by":"publisher","first-page":"e2200081","DOI":"10.1056\/EVIDoa2100018","article-title":"Sublingual MV140 for prevention of recurrent urinary tract infections","volume":"1","author":"Lorenzo-G\u00f3mez","year":"2022","journal-title":"NEJM. Evid."},{"key":"ref21","doi-asserted-by":"publisher","first-page":"612269","DOI":"10.3389\/fimmu.2020.612269","article-title":"A combination of polybacterial MV140 and Candida albicans V132 as a potential novel trained immunity-based vaccine for genitourinary tract infections","volume":"11","author":"Martin-Cruz","year":"2021","journal-title":"Front. Immunol."},{"key":"ref22","doi-asserted-by":"publisher","first-page":"1142","DOI":"10.1093\/infdis\/165.6.1142","article-title":"Hydrogen peroxide production by Lactobacillus species: correlation with susceptibility to the spermicidal compound nonoxynol-9","volume":"165","author":"McGroarty","year":"1992","journal-title":"J. Infect. Dis."},{"key":"ref23","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1016\/j.maturitas.2016.05.015","article-title":"Menopause and the vaginal microbiome","volume":"91","author":"Muhleisen","year":"2016","journal-title":"Maturitas"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"485","DOI":"10.1086\/318070","article-title":"Assessment of the capacity of Lactobacillus to inhibit the growth of uropathogens and block their adhesion to vaginal epithelial cells","volume":"183","author":"Osset","year":"2001","journal-title":"J. Infect. Dis."},{"key":"ref25","doi-asserted-by":"publisher","first-page":"1054","DOI":"10.1086\/378203","article-title":"Prevalence and determinants of vaginal flora alterations in postmenopausal women","volume":"188","author":"Pabich","year":"2003","journal-title":"J. Infect. Dis."},{"key":"ref26","doi-asserted-by":"publisher","first-page":"753","DOI":"10.1056\/NEJM199309093291102","article-title":"A controlled trial of intravaginal estriol in postmenopausal women with recurrent urinary tract infections","volume":"329","author":"Raz","year":"1993","journal-title":"N. Engl. J. Med."},{"key":"ref27","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1139\/m88-060","article-title":"Effect of antibiotic treatment on receptivity of uroepithelial cells to uropathogens","volume":"34","author":"Reid","year":"1998","journal-title":"Can. J. Microbiol."},{"key":"ref28","doi-asserted-by":"publisher","first-page":"1026","DOI":"10.1111\/iju.14636","article-title":"Efficacy of Lactobacillus vaginal suppositories for the prevention of recurrent cystitis: a phase II clinical trial","volume":"28","author":"Sadahira","year":"2021","journal-title":"Int. J. Urol."},{"key":"ref29","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1016\/s0022-5347(17)57950-1","article-title":"Studies of introital colonization in women with recurrent urinary infections. IX. The role of antimicrobial therapy","volume":"118","author":"Schaeffer","year":"1977","journal-title":"J. Urol."},{"key":"ref30","doi-asserted-by":"publisher","first-page":"1159","DOI":"10.1007\/s00203-020-02114-4","article-title":"Comparison of different hypervariable regions of 16S rRNA for taxonomic profiling of vaginal microbiota using next-generation sequencing","volume":"203","author":"Sirichoat","year":"2021","journal-title":"Arch. Microbiol."},{"key":"ref31","doi-asserted-by":"publisher","first-page":"747","DOI":"10.3920\/BM2014.0154","article-title":"Comparison of detection methods for vaginal lactobacilli","volume":"6","author":"Smidt","year":"2015","journal-title":"Benef Microbes."},{"key":"ref32","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1016\/s0022-5347(17)60454-3","article-title":"The role of introital enterobacteria in recurrent urinary infections","volume":"109","author":"Stamey","year":"1973","journal-title":"J. Urol."},{"key":"ref33","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1128\/microbiolspec.UTI-0025-2016","article-title":"The vaginal microbiota and urinary tract infection","volume":"4","author":"Stapleton","year":"2016","journal-title":"Microbiol. Spectr."},{"key":"ref34","doi-asserted-by":"publisher","first-page":"1212","DOI":"10.1093\/cid\/cir183","article-title":"Randomized, placebo-controlled phase 2 trial of a Lactobacillus crispatus probiotic given intravaginally for prevention of recurrent urinary tract infection","volume":"52","author":"Stapleton","year":"2011","journal-title":"Clin. Infect. Dis."},{"key":"ref35","doi-asserted-by":"publisher","first-page":"782","DOI":"10.1016\/j.resmic.2017.04.001","article-title":"The role of lactic acid production by probiotic Lactobacillus species in vaginal health","volume":"168","author":"Tachedjian","year":"2017","journal-title":"Res. Microbiol."},{"key":"ref36","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1016\/j.ijantimicag.2006.05.008","article-title":"A pilot study evaluating the safety and effectiveness of Lactobacillus vaginal suppositories in patients with recurrent urinary tract infection","volume":"28","author":"Uehara","year":"2006","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"1431","DOI":"10.1086\/324445","article-title":"Factors associated with acquisition of, or persistent colonization by, vaginal lactobacilli: role of hydrogen peroxide production","volume":"184","author":"Vallor","year":"2001","journal-title":"J. Infect. Dis."},{"key":"ref38","doi-asserted-by":"publisher","first-page":"e105998","DOI":"10.1371\/journal.pone.0105998","article-title":"The vaginal microbiota: what have we learned after a decade of molecular characterization?","volume":"9","author":"van de Wijgert","year":"2014","journal-title":"PLoS One"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"630","DOI":"10.1038\/s41564-022-01107-x","article-title":"Longitudinal multi-omics analyses link gut microbiome dysbiosis with recurrent urinary tract infections in women","volume":"7","author":"Worby","year":"2022","journal-title":"Nat. Microbiol."},{"key":"ref40","doi-asserted-by":"publisher","first-page":"1097","DOI":"10.3390\/jcm10051097","article-title":"Urinary microbiome characteristics in female patients with acute uncomplicated cystitis and recurrent cystitis","volume":"10","author":"Yoo","year":"2021","journal-title":"J. Clin. Med."},{"key":"ref41","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1007\/s11274-018-2480-1","article-title":"The aggregation-promoting factor in Lactobacillus delbrueckii ssp. bulgaricus: confirmation of the presence and expression of the apf gene and in silico analysis of the corresponding protein","volume":"34","author":"Yungareva","year":"2018","journal-title":"World J. Microbiol. Biotechnol."},{"key":"ref42","doi-asserted-by":"publisher","first-page":"729","DOI":"10.1099\/jmm.0.038687-0","article-title":"Qualitative and semiquantitative analysis of Lactobacillus species in the vaginas of healthy fertile and postmenopausal Chinese women","volume":"61","author":"Zhang","year":"2012","journal-title":"J. Med. Microbiol."}],"container-title":["Frontiers in Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2023.1187479\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,18]],"date-time":"2023-05-18T01:51:30Z","timestamp":1684374690000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2023.1187479\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,18]]},"references-count":42,"alternative-id":["10.3389\/fmicb.2023.1187479"],"URL":"https:\/\/doi.org\/10.3389\/fmicb.2023.1187479","relation":{},"ISSN":["1664-302X"],"issn-type":[{"value":"1664-302X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,18]]},"article-number":"1187479"}}