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Cited by 19Reproductive tract infections researchUrinary Tract Infections ManagementGut microbiota and health

Etiology of recurrent cystitis in postmenopausal women based on vaginal microbiota and the role of Lactobacillus vaginal suppository

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Sekito, Takanori, Wada, Koichiro, Ishii, Ayano, Iwata, Takehiro, Matsubara, Takehiro, Tomida, Shuta, Watanabe, Masami, Araki, Motoo +1 more·2023·Frontiers in Microbiology
DOI 10.3389/fmicb.2023.1187479PMC PMC10232810
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Abstract

Background: The vaginal microbiota can be altered by uropathogenic bacteria associated with recurrent cystitis (RC), and the vaginal administration of Lactobacillus 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 Lactobacillus . Methods: Vaginal samples obtained from 39 postmenopausal women were classified into four groups: healthy controls; uncomplicated cystitis; RC; and prevention (prevented RC by Lactobacillus crispatus -containing vaginal suppositories). Principal coordinate analysis and beta-diversity analysis was used to assess 16S rRNA gene sequencing data from the vaginal microbiome. Results: 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 ( p = 0.045), and between the RC group and the uncomplicated cystitis group or the healthy group ( p = 0.001, p = 0.001, respectively). There were no significant differences between the RC group and the prevention group ( p = 0.446). The top six taxa were as follows: Prevotella, Lactobacillus, Streptococcus, Enterobacteriaceae, Anaerococcus, and Bifidobacterium . Among patients with RC, Lactobacillus was undetectable before administration of suppositories, while the median relative abundance of Lactobacillus was 19% during administration of suppositories ( p = 0.0211), reducing the average cystitis episodes per year (6.3 vs. 2.4, p = 0.0015). Conclusion: The vaginal microbiota of postmenopausal women with RC is differed from healthy controls and uncomplicated cystitis in terms of lack of Lactobacillus and relatively dominant of Enterobacteriaceae . Vaginal administration of Lactobacillus -containing suppositories can prevent RC by stabilizing vaginal dysbiosis and causing a loss of pathogenic bacteria virulence.

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  • Recurrent UTIs represent a significant clinical and economic burden, particularly in postmenopausal women, where standard therapies often fail to prevent recurrence.

    “Therefore, recurrent UTIs (rUTIs) represent a significant clinical and economic burden, particularly in postmenopausal women, where standard therapies often fail to prevent recurrence [6].”

    From Vaginal microbiota and urinary tract infections in women: the protective role of vaginal lactobacilli in counteracting urinary tract infections occurrence and recurrence (2026) · cites this paper as [6]

    The Introduction (page unavailable) says recurrent cystitis can be burdensome in postmenopausal women and that frequent, long-term antimicrobial use can lead to intractable cystitis. It does not identify an economic burden or establish that standard therapies often fail to prevent recurrence. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • Depletion of Lactobacillus species has been linked to increased colonization by E. coli and other pathogens, and this dysbiosis is related to bacterial vaginosis.

    “Depletion of these Lactobacillus species has been linked to increased colonization by E. coli and other pathogens, and this dysbiosis is related to the most prevalent vaginal infection in women: Bacterial Vaginosis (BV) [2, 6].”

    From Vaginal microbiota and urinary tract infections in women: the protective role of vaginal lactobacilli in counteracting urinary tract infections occurrence and recurrence (2026) · cites this paper as [6]

    The Discussion (page unavailable) links low vaginal Lactobacillus with predominant Enterobacteriaceae in postmenopausal women with recurrent cystitis and describes Lactobacillus inhibition of uropathogenic E. coli. It relates this dysbiosis to recurrent cystitis, not bacterial vaginosis; the cited passages also do not establish that BV is the most prevalent vaginal infection. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • Several recent clinical studies have demonstrated that topical Lactobacillus therapy as 'complementary treatment' after antibiotic therapy, especially with vaginal suppositories, can significantly reduce the frequency of rUTIs, even in postmenopausal women with refractory infections.

    “Several recent clinical studies have demonstrated that topical Lactobacillus therapy as 'complementary treatment' after antibiotic therapy, especially with vaginal suppositories, can significantly reduce the frequency of rUTIs, even in postmenopausal women with refractory infections [6, 14-16], highlighting the therapeutic potential of microbiome-targeted strategies.”

    From Vaginal microbiota and urinary tract infections in women: the protective role of vaginal lactobacilli in counteracting urinary tract infections occurrence and recurrence (2026) · cites this paper as [6]

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  • Dysbiosis, whether induced by antibiotics, hormonal changes, or behavioral factors, can compromise mucosal defenses and promote pathogen colonization.

    “These shifts support evidence that dysbiosis - whether induced by antibiotics, hormonal changes, or behavioral factors - can compromise mucosal defenses and promote pathogen colonization [2, 6].”

    From Vaginal microbiota and urinary tract infections in women: the protective role of vaginal lactobacilli in counteracting urinary tract infections occurrence and recurrence (2026) · cites this paper as [6]

    The Introduction (page unavailable) reports changes in vaginal microbiota in postmenopausal women, and the Discussion (page unavailable) says repeated antibiotic exposure may cause dysbiosis. The Discussion also describes how Lactobacillus inhibits vaginal uropathogen colonization, supporting the proposed protective role of the microbiota. The paper does not address behavioral factors as a cause of dysbiosis or directly establish that dysbiosis compromises mucosal defenses. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • The bacteria usually responsible for urinary tract infections are the same as those responsible for bacterial vaginosis.

    “In recent years, several authors have reported that the bacteria usually responsible for UTIs are the same as those responsible for BV, which is the most common asymptomatic vaginal infection in women, and the idea of using a symbiotic vaginal approach to prevent UTIs in women seems to be intriguing [6, 70].”

    From Vaginal microbiota and urinary tract infections in women: the protective role of vaginal lactobacilli in counteracting urinary tract infections occurrence and recurrence (2026) · cites this paper as [6]

    The Introduction (page unavailable) says vaginal colonization with E. coli can contribute to recurrent cystitis, supporting a link between vaginal bacteria and UTIs. It does not say that the bacteria usually responsible for UTIs are the same as those responsible for bacterial vaginosis; that broader comparison is unsupported. (LLM, conf=0.78)

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Authors
Sekito, T., Wada, K., Ishii, A., Iwata, T., Matsubara, T., Tomida, S., Watanabe, M., Araki, M., & Sadahira, T.
Affiliations
  • Okayama University (JP)
  • Shimane University (JP)
  • Okayama University Hospital (JP)
Corresponding author
Sadahira, Takuya
ORCID
Venue
Frontiers in Microbiology
Publisher
Frontiers Media SA
Published
2023-05-18
Volume
14
Pages
1187479-1187479
ISSN
1664-302X (ISSN-L)
DOI
10.3389/fmicb.2023.1187479
PMC
PMC10232810
OpenAlex
W4377107967
Cited by
19
References
1
Citations by year
2026: 11 · 2025: 2 · 2024: 5 · 2023: 1
FWCI
3.46
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Microbiology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Institutional Repositories DataBase (IRDB) (submittedVersion, cc-by)
  • Okayama University Scientific Achievement Repository (Okayama University) (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
Chemotherapy Foundation
Topics
  • Life Sciences › Immunology and Microbiology › Microbiology › Reproductive tract infections research
  • Health Sciences › Medicine › Epidemiology › Urinary Tract Infections Management
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
Keywords
recurrent cystitis, postmenopausal women, vaginal microbiota, Lactobacillus crispatus, uropathogenic bacteria, vaginal dysbiosis, beta diversity, 16S rRNA gene sequencing, Prevotella, Streptococcus

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