Lactobacillus crispatus

We aimed at assessing the evidence for an effect on vaginal dysbiosis by oral administration of a mixture of Lactobacillus strains isolated from vaginal microbiota. For this purpose, we systematically reviewed the literature for randomised clinical trials (RCTs) in which the effect of oral administration of a mixture of four Lactobacillus strains (Lactobacillus crispatus LbV 88 (DSM 22566), Lactobacillus gasseri LbV 150N (DSM 22583), Lactobacillus jensenii LbV 116 (DSM 22567) and Lactobacillus rhamnosus LbV96 (DSM 22560)) on vaginal dysbiosis was examined based on Nugent score. Four RCTs were identified: a double-blind (DB)-RCT in 60 male-to-female transsexual women with neovagina; an open label RCT in 60 pregnant women with herpes virus infection; a DB-RCT in 36 women with bacterial vaginosis; a DB-RCT in 22 postmenopausal breast cancer patients receiving chemotherapy. Only in the three DB-RCTs Nugent score was assessed. The meta-analysis of these trials showed a significant reduction of Nugent score by probiotics compared to placebo in the fixed (standardised mean differences (SMD) -0.561; confidence interval (CI) -0.935 to -0.186; P=0.004 and random effect models (SMD -0.561; CI -0.935 to -0.186; P=0.004). The odds ratio (OR) of the cases presenting with improved Nugent score after probiotics compared to placebo treatment showed a significant effect in the fixed (OR=3.936; CI 1.702 to 9.100; P=0.001) and random effect model (OR=3.902; CI 1.681 to 9.059; P=0.001) Cochran's Q and I2 statistics showed no heterogeneity. This meta-analysis indicates that the oral intake of the pertinent Lactobacillus strains improves the microbial pattern in vaginal dysbiosis.

Bacterial vaginosis (BV) affects >25% of women worldwide and often recurs after standard-of-care metronidazole (MTZ) treatment. LACTIN-V, a live biotherapeutic product (LBP) containing Lactobacillus crispatus strain CTV-05, significantly reduced recurrent BV in a phase 2b clinical trial, but efficacy was incomplete. Here, we characterize microbiota and immune effects using multi-omics and define correlates of treatment success. By week 12, an L. crispatus-dominant microbiota was achieved in 30% of LBP recipients compared with 9% of placebo recipients (benefit ratio: 3.31; p < 0.005). This is primarily due to CTV-05, but native L. crispatus strains are also present and increase over time. Inflammatory cytokines decrease in both arms after MTZ but return to baseline in placebo recipients. Successful L. crispatus colonization is associated with pre-MTZ microbiota, baseline inflammatory profiles, post-MTZ bacterial load, and clinical and behavioral variables. These findings elucidate LBP microbiota effects and identify predictors of treatment success, informing improved intervention strategies to advance women's health.

Bacterial vaginosis (BV) is characterized by high microbial diversity. High recurrence rates following antibiotics may stem from poor recolonization by protective Lactobacillus species. This phase 1 randomized trial in the United States and South Africa evaluated two vaginally delivered live biotherapeutic products (LBPs) containing multiple Lactobacillus crispatus strains. After metronidazole treatment for BV, participants received either a placebo or 3 or 7 days of active LBPs. LBP strains were detected by metagenomics in 66.1% (47/71) of participants in the active arms in the first 5 weeks. Among those, nearly half (49%, 23/47) remained colonized at 12 weeks despite the short initial treatment course. Participants were most often colonized by one of three component strains, with no geographic differences in strain colonization observed. LBPs were safe, acceptable, and well tolerated, with no serious adverse events (AEs) reported. These results provide a foundation for the development of transformational interventions aimed at optimizing the vaginal microbiome.

Background and Objectives: Vulvo-vaginal atrophy (VVA), a prevalent condition among postmenopausal women, significantly impairs quality of life through symptoms like vaginal dryness, dyspareunia, and burning. Non-hormonal treatments, such as CO2 laser therapy, have shown promise in managing VVA symptoms with minimal side effects. The addition of adjunctive treatments may enhance efficacy and mitigate possible adverse effects. To evaluate the combined efficacy and safety of CO2 laser therapy and a collagen-based cream in treating VVA and to explore their potential impact on the vaginal microbiome. Materials and Methods: This was a single-center, randomized, interventional. Sixty postmenopausal women diagnosed with VVA were randomized into two groups: a control group receiving laser-only treatment and a treatment group receiving laser therapy with daily collagen-based cream application. Primary outcome measures included symptom improvement on the Visual Analog Scale (VAS) for VVA-associated symptoms. Secondary outcomes involved microbiome composition analysis. Results: Both groups showed significant symptom improvement, with the combination therapy group demonstrating superior reductions in burning, dyspareunia, and vaginal dryness (p < 0.05). Microbiome analysis revealed increased levels of beneficial species (Lactobacillus iners and Lactobacillus crispatus) and decreased pathogenic bacteria (Gardnerella vaginalis and Atopobium vaginae) in the treatment group, though these changes were not statistically significant. Mild side effects, such as burning and swelling in the first days following the treatment, were less frequent in the combination therapy group, likely due to the anti-inflammatory effects of the collagen-based cream. Conclusions: This study provides evidence supporting the use of CO2 laser therapy with collagen-based cream as an effective and well-tolerated treatment for VVA in postmenopausal women, achieving significant symptom relief. The combined therapy approach holds potential for enhanced efficacy and reduced side effects compared to laser-only treatment, offering a promising alternative for women ineligible for hormone-based therapies.

BACKGROUND: Recurrent vulvovaginal candidiasis (RVVC) is a common condition characterized by frequent relapses, often without a clearly identifiable cause. Fluconazole (FLZ) is the standard treatment but concerns about emerging resistance and drug interaction highlight the need for alternative therapies. Chlorhexidine gluconate (CHG), known for its antifungal and biofilm-disrupting properties, has been proposed as a potential alternative. OBJECTIVE: To evaluate the efficacy, tolerability, and microbiome impact of a vaginal CHG formulation compared to oral FLZ in the treatment of RVVC caused by Candida albicans. METHODS: An open label randomized non-inferiority trial was conducted to compare vaginal CHG and FLZ treatments. Primary outcome was negative cultures for C. albicans. Resistance profiles and changes in the vaginal microbiome composition were also assessed. RESULTS: The study was terminated early due to local irritation associated with CHG and the study design was transitioned into a pilot study. CHG treatment showed comparable efficacy to FLZ in clearing C. albicans infections and preventing recurrences, although the sample size was limited. All 11 participants in the FLZ group cleared the infection after one week treatment, compared to 9 out 11 in the CHG group. No harmful changes to the vaginal microbiome were observed in the CGH or FLZ group. FLZ promoted a shift toward Lactobacillus crispatus dominance, unlike CHG. Notably, 16% of C. albicans isolates exhibited reduced susceptibility or resistance to FLZ. CONCLUSION: Due to the limited number of participants, we cannot conclusively determine whether CHG is non-inferior to FLZ in terms of efficacy for clearing acute C. albicans infections or preventing recurrences. While the current CHG formulation caused local irritation and is not suitable for clinical use, its antifungal and biofilm-inhibiting properties remain promising. Further development of less irritative CHG formulations may offer a valuable alternative for RVVC treatment, particularly in the context of rising FLZ resistance. Copyright: © 2026 Alvendal et al. This is an open access article distributed under the terms of the Creative Commons

A clinical trial of a multi-strain vaginal synbiotic (NCT05659745, registered 12/19/2022 at clinicaltrials.gov) led to an optimal vaginal microbiome dominated by L. crispatus (CST I). The synbiotic led to a significant increase in L. crispatus compared to placebo (p < 0.05), and conversion to CST I was significantly higher with the vaginal synbiotic than with placebo (90 vs 11%; p < 0.002). Mechanistically, the synbiotic reduced Gardnerella vaginalis and Candida, clinically important microbes. © 2025. The Author(s). Lactobacillus gasseri CECT 30648 shows probiotic characteristics and colonizes the vagina of healthy women after oral administration. Perez M(#)(1), Armengol E(#)(1)(2), Del Casale A(3), Campedelli I(3), Aldea-Perona A(4)(5)(6), Pérez Otero M(4)(5), Rodriguez-Palmero M(1), Espadaler-Mazo J(1), Huedo P(1)(2). Author information: (1)R&D Department, AB-Biotics S.A. (Part of Kaneka Corporation), Barcelona, Spain. (2)Basic Sciences Department, Universitat Internacional de Catalunya, Barcelona, Spain. (3)Open Innovation Department, MICROBION srl, Verona, Italy. (4)Clinical Pharmacology, Hospital del Mar, Barcelona, Spain. (5)Hospital del Mar Medical Research Institute, Barcelona, Spain. (6)Universitat Pompeu Fabra, Barcelona, Spain. (#)Contributed equally Vaginal dysbiosis is linked to recurrent infections and reproductive complications. Probiotics may restore vaginal microbiota, but there is modest evidence to support vaginal colonization after oral administration. This work aimed to screen a vaginal lactobacilli collection (n = 45) and assess vaginal colonization of selected candidates. Lactobacillus gasseri CECT 30648 (Lg) and Lactobacillus crispatus CECT 30647 (Lc) showed excellent in vitro attributes, including antagonism against 10 urogenital pathogens, resistance to gastrointestinal tract and vaginal environment-including high concentrations of biogenic amines-and adhesion to vaginal epithelium. Forty-eight healthy women (18-45 years old) were randomly allocated to consume daily a capsule containing Lg (109 CFU), a combination of Lg plus Lc (1.5 × 109 CFU), or placebo for up to 18 days (between menses). Volunteers collected vaginal samples ever

7. Microbiol Spectr. 2025 Sep 2;13(9):e0021125. doi: 10.1128/spectrum.00211-25. Epub 2025 Aug 7. Lactobacillus gasseri CECT 30648 shows probiotic characteristics and colonizes the vagina of healthy women after oral administration. Perez M(#)(1), Armengol E(#)(1)(2), Del Casale A(3), Campedelli I

The primary aim of the present randomised, double-blind, placebo-controlled trial was to investigate whether clindamycin and live Lactobacillus crispatus CTV-05 (LACTIN-V) would improve clinical pregnancy rates in IVF patients with abnormal vaginal microbiota (AVM) defined by high quantitative PCR loads of Fannyhessea vaginae and Gardnerella spp. IVF patients were randomised prior to embryo transfer into three parallel groups 1:1:1. Group one (CLLA) received clindamycin 300 mg ×2 daily for 7 days followed by vaginal LACTIN-V until the day of pregnancy scan. Group two (CLPL) received clindamycin and placebo LACTIN-V, and finally, group three (PLPL) received an identical placebo of both drugs. A total of 1533 patients were screened, and 338 patients were randomised. The clinical pregnancy rates per embryo transfer were 42% (95%CI 32-52%), 46% (95%CI 36-56%) and 45% (95%CI 35-56%) in the CLLA, CLPL, PLPL groups respectively. Thus, treatment of AVM did not improve reproductive outcome. The EudraCT (European Union Drug Regulating Authorities Clinical Trials Database) clinical trial identifier is 2016-002385-31; first registration day 2016-07-11. © 2025. The Author(s).

BACKGROUND: Absence of vaginal lactobacilli and accompanying genital inflammation is associated with HIV acquisition. We aimed to assess how a vaginal live biotherapeutic containing Lactobacillus crispatus affects cervicovaginal microbiota and markers of HIV susceptibility in South African women. METHODS: This randomised, placebo-controlled, phase 2 trial evaluated LACTIN-V (L crispatus CTV-05), a vaginal live biotherapeutic, compared with placebo in cisgender women in South Africa, aged 18-23 years, recruited at a community-based research clinic. Eligible participants with a Nugent score of 4-10 (indicating intermediate vaginal microbiota or bacterial vaginosis) completed 7 days of oral metronidazole and were randomly assigned (2:1) to LACTIN-V (2 × 109 colony forming units per dose) or placebo (the substrate alone) via an independently generated randomisation sequence. Pharmacists, participants, and investigators were masked to treatment assignment. The study product (or placebo) was dosed daily for 5 days in week 1, then twice per week for an additional 3 weeks. Adverse events were evaluated 4 weeks and 8 weeks after starting the study product. Vaginal swabs (for 16S rRNA sequencing of the vaginal microbiome) and cervicovaginal lavage (for Luminex analysis of immune markers) were collected before metronidazole treatment, before study product (or placebo) administration, and at the week 4 and week 8 follow-up visits. An endocervical cytobrush for flow cytometry analysis of immune cell populations (including CD3+CD4+ T cells, and presence of CCR5 and the activation markers CD38 or HLA-DR) was collected before study product use and at 4 weeks and 8 weeks after study product use. The coprimary outcomes for the trial were (1) safety and acceptability of LACTIN-V, as measured by number of adverse events and a validated questionnaire; (2) presence of a Lactobacillus-dominant vaginal microbial community by 16S rRNA gene sequencing at week 4 and week 8; and (3) comparison of change in genital tract inflammatory markers from before metronidazole treatment to week 4 and week 8 between groups. Safety analyses were done in the intention-to-treat population and efficacy an

Viral infections are a global public health threat, reaffirming the importance of immune function. We previously identified Lactobacillus crispatus strain KT-11 (KT-11) and found that heat-sterilized KT-11 affect counts of T cell and dendritic cell in vitro, as well as promoted immunoglobulin A production and prevented weight loss caused by influenza virus infection in vivo. It was hypothesized that heat-sterilized KT-11 affects immune cell count/activity even in healthy individuals. We conducted a pilot study to examine the design to verify the effects of heat-sterilized KT-11 supplementation on immune cell count/activity and physical condition. This was a pilot randomized, double-blind, placebo-controlled, parallel-group study including 22 healthy adults who consumed either KT-11 or placebo for 4 weeks. Immunological status (immune cell count/activity and its score) and various immune-related indicators including SARS-CoV-2 immunoglobulin G antibody were assessed, and a physical condition questionnaire was administered. The primary outcome was immune cell count/activity (T cell subsets, B cell, natural killer cell) and overall immunological status score after 4 weeks. Two patients were excluded because of noncompliance; the final analysis included 20 participants (10 participants/group). The KT-11 group had a significantly higher CD3+ T cell count versus placebo group. The female subgroup also had a significantly higher CD8+CD28+ T cell count. Although the KT-11 group showed no changes in SARS-CoV-2 immunoglobulin G titer, it had fewer self-reported common cold-like symptoms, particularly fatigue. This pilot study showed that KT-11 affected immune cell profiles, suggesting that the feasibility of a verification study. This trial was registered at UMIN Clinical Trials Registry (UMIN000046991).

PURPOSE: Non-optimal vaginal microbiota lacking lactobacilli and comprising a wide array of anaerobic bacteria, typified by community state type (CST) IV, have been associated with adverse gynecological and pregnancy outcomes. Here, we investigate the stability of the vaginal microbiota sampled every 6 months over 18 months and how samples distantly collected combined with exposures could provide insight on future microbiota compositional changes. METHODS: Vaginal microbiota dynamics were analyzed in 241 female students aged 18-24 years and negative for Chlamydia trachomatis and Neisseria gonorrhoeae. The vaginal microbiota was characterized using 16S rRNA gene amplicon sequencing and assigned to CSTs. Vaginal microbiota longitudinal profiles were determined through hierarchical clustering. RESULTS: At baseline, 11.2% of participants had a CST IV, 40.5% a CST I (Lactobacillus crispatus-dominated), and 38.1% a CST III (Lactobacillus iners-dominated). A total of 345 CST transitions were observed over the study period. Pain during sexual intercourse was associated with a higher probability of transition from CST III to CST IV, while self-reported yeast infection was associated with a higher probability of transition from CST IV to CST I. Over the study period, 32.0% participants displayed a stable CST trajectory. Composition of the vaginal microbiota of a single sample predicted with good accuracy the CST trajectory over the following 18 months. CONCLUSION: Vaginal longitudinal CST patterns over 18 months could be clustered into three main groups of trajectories. Performing molecular characterization at a single time point could contribute to improved preventive care and optimization of young women's reproductive and sexual health. CLINICALTRIALS: gov Identifier: NCT02904811. Registration date: September 19, 2016. © 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

SlpB, a surface layer protein isolated from Lactobacillus crispatus, has the potential to enhance the antimicrobial activity of nisin. Previous research indicated that, when combined with nisin, SlpB acted synergistically to inhibit Staphylococcus saprophyticus growth, thus extending the shelf life of chicken meat. In order to understand how SlpB enhances the antibacterial activity of nisin, electron microscopy, confocal laser scanning microscopy, flow cytometry and transmembrane electrical potential analysis were used to study cell wall organization and cell membrane integrity. No remarkable bacteriolytic effects were observed, indicating that cell death could not be attributed to cell lysis, although SlpB caused dramatic modifications of cell wall, thereby altering cell shape. The combination of SlpB and nisin also induced the release of ATP or UV-absorbing materials, as well as sudden dissipation of the transmembrane electrical potential by compromising membrane integrity. Considering that SlpB led to structural disorganization of the cell wall, and nisin access is enhanced to form a stable pore, cell death is a predictable outcome. SlpB significantly enhanced the effect of nisin at half of the minimum inhibitory concentration, which resulted in cell death by destroying the cell wall and cell membrane, therefore providing a new, feasible approach in food preservation.

Ciprofloxacin and streptomycin are frequently prescribed for the treatment of medical conditions originating due to infection by Pseudomonas aeruginosa. However, fluoroquinolone administration has been linked to the outgrowth of Clostridium difficile pathogen, especially in immunocompromised patients. Secondly, frequent administration of antibiotics may lead to development of resistance in the pathogens. Thus, there is a need to explore innovative adjunct therapies to lower the therapeutic doses of the antibiotics. Herein, we evaluated the synergism, if any, between conventional antibiotics and the cell-free supernatant (CFS) of vaginal Lactobacillus crispatus 156 against P. aeruginosa MTCC 741. L. crispatus 156 was isolated from the human vaginal tract, and its CFS had broad-spectrum antimicrobial activity against various Gram-positive and Gram-negative pathogens, including P. aeruginosa. The inhibitory substance present in the CFS completely lost its activity after treatment with proteinases and was resistant to temperatures up to 80 °C and pH ranging from 2 to 6. The cumulative production of the inhibitory substance in CFS was studied, and it showed that the secretion of the inhibitory substance was initiated in middle log phase of growth and peaked in late log phase. Further, CFS synergized the activities of ciprofloxacin, moxifloxacin, and streptomycin as evaluated in terms of checkerboard titrations. It lowered the minimum inhibitory concentration (MIC) of ciprofloxacin by almost 30 times and MIC of both moxifloxacin and streptomycin by 8 times. Interestingly, pepsin treatment of CFS caused the complete abrogation of its synergistic effect with all the three antibiotics. Thus, from the study, it can be concluded that probiotic-based alternative therapeutic regimen can be designed for the treatment of P. aeruginosa infections.

BACKGROUND: Tuberculosis remains an infectious disease of global concern, with potential impacts on respiratory and intestinal microbiota owing to prolonged broad-spectrum antibiotic therapy. Despite its potential to cause infertility, the vaginal microbiota of women with genital tuberculosis remains poorly understood. We comprehensively analyzed the vaginal microbiota in Chinese women with genital tuberculosis. RESULTS: We recruited women with pelvic (n = 28), endometrial (n = 16), and pulmonary (n = 12) tuberculosis as the research group, and healthy women (n = 11) as the control group. Vaginal discharges were collected for metagenomic analysis of its microbiota. The alpha diversity of the vaginal microbiota in women with genital tuberculosis was slightly higher than that in healthy women, though the difference was not statistically significant (P = 0.23). Similarly, no significant differences in alpha diversity were observed between women with genital and pulmonary tuberculosis (P = 0.82) or between those with pelvic and endometrial tuberculosis (P = 0.82). Notably, the lowest alpha diversity was recorded six months to one year after initiating anti-tuberculosis treatment, with this decline being statistically significant (P = 0.023). The dominance of Lactobacillus iners in the vaginal microbiota was more common in women with genital tuberculosis than that of Lactobacillus crispatus. Furthermore, the abundance of short-chain fatty acid -producing anaerobes, such as Actinomycetes, Streptococcus, and Finegoldia, were significantly increased. Short-chain fatty acid precursor pathways, including the ko03010 ribosome pathway, ko00970 aminoacyl-tRNA synthesis, ko00230 purine metabolism, ko00240 pyrimidine metabolism, and ko00010 glycolysis gluconeogenesis pathway, were significantly upregulated in women with endometrial tuberculosis. CONCLUSIONS: Extrapulmonary tuberculosis, particularly genital tuberculosis and its associated vaginal dysbiosis impacts female fecundity. Vaginal dysbiosis is more pronounced when M. tuberculosis invades the endometrium. Given the effect of antibiotics on vaginal flora, probiotic combined interventions could be used as a future resear

Miscarriage, the loss of a pregnancy before viability, can be sporadic or recurrent. Emerging evidence links miscarriage to specific microbiota compositions within the female reproductive tract (FRT). This systematic review aims to synthesise evidence on the association between sporadic and recurrent miscarriage and FRT microbiota composition, as assessed using metataxonomic profiling approaches. A systematic analysis of the 43 included studies, sampling the vaginal, cervical and endometrial microbiota supported an association between reduced Lactobacillus abundance and miscarriage, making it a potential target for therapeutic intervention. However, consistent changes in alpha and beta diversity were not observed and there was a lack of reproducibility for other compositional changes. This review also highlighted concerns about the significant bias introduced due to methodological variations and emphasises the need for future standardisation of microbial sampling, sequencing, and reporting to allow accurate comparison of results and to reduce research waste. © 2026. The Author(s).

The role of vaginal dysbiosis in the progression of human papilloma virus (HPV) associated cervical lesions has gained attention in recent years. While many studies use 16S rRNA gene sequencing for microbiota analysis, shotgun metagenomic sequencing offers higher taxonomic resolution and insights into microbial gene functions and pathways. This systematic review evaluates the relationship between compositional and functional changes in the vaginal microbiome during HPV infection and cervical lesion progression. A literature search was performed according to PRISMA guidelines in PubMed, Web of Science, Scopus, and ScienceDirect databases. Seven studies utilizing metagenomic sequencing in patients with HPV infection or HPV-associated cervical lesions were included. Progression from HPV infection to cervical lesions and cancer was associated with a reduction in Lactobacillus species (particularly Lactobacillus crispatus) and an enrichment of anaerobic and pathogenic species, especially Gardnerella vaginalis. Heterogeneous enriched metabolic pathways were also identified, indicating functional shifts during lesion progression. As most studies were conducted in Asia, further research in diverse regions is needed to improve the generalizability of findings. Future studies employing metagenomic sequencing may help identify biomarkers for early pre-cancerous lesions and clarify the role of vaginal microbiota in persistent HPV infection and cervical dysplasia.

BACKGROUND: Latina women experience disproportionately higher rates of HPV infection, persistence, and progression to cervical dysplasia and cancer compared to other racial-ethnic groups. This systematic review explores the relationship between the cervicovaginal microbiome and human papillomavirus infection, cervical dysplasia, and cervical cancer in Latinas. METHODS: The review abides by the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. PubMed, EMBASE, and Scopus databases were searched from January 2000 through November 11, 2022. The review included observational studies reporting on the cervicovaginal microbiota in premenopausal Latina women with human papillomavirus infection, cervical dysplasia, and cervical cancer. RESULTS: Twenty-five articles were eligible for final inclusion (N = 131,183). Forty-two unique bacteria were reported in the cervicovaginal microbiome of Latinas. Seven bacteria: Lactobacillus crispatus, Lactobacillus iners, Chlamydia trachomatis, Prevotella spp., Prevotella amnii, Fusobacterium spp. and Sneathia spp. were enriched across multiple stages of cervical carcinogenesis in Latinas. Therefore, the total number of reported bacteria includes four bacteria associated with the healthy state, 16 bacteria enriched in human papillomavirus outcomes, 24 unique bacteria associated with abnormal cytology/dysplasia, and five bacteria associated with cervical cancer. Furthermore, three studies reported significantly higher alpha and beta diversity in Latinas with cervical dysplasia and cancer compared to controls. Lactobacillus depletion and an increased abundance of L. iners in Latinas compared to non-Latinas, regardless of human papillomavirus status or lesions, were observed. CONCLUSIONS: The identification of 42 unique bacteria and their enrichment in cervical carcinogenesis can guide future cervicovaginal microbiome research to better inform cervical cancer prevention strategies in Latinas. © 2024. The Author(s).

Objective: With a global incidence of more than 10%, preterm birth (PTB) remains a significant concern. The vaginal microbiome strongly influences the well-being of the female reproductive tract. This study examines the correlation between changes in Lactobacillus vaginal microbiota and the PTB risk. Materials and Methods: A thorough search of PubMed, Web of Science, Cochrane Library, and EMBASE was conducted to locate studies that examined the association between changes in Lactobacillus vaginal microbiota and the risk of PTB from January 1, 2010, to January 30, 2023. The risk of PTB was determined by calculating odds ratios (ORs) with 95% confidence intervals (CIs). Results: In our analysis, there were 11 studies with 1577 pregnant women. The findings revealed a significant negative correlation between higher Lactobacillus abundance and the PTB risk (OR = 0.49, 95% CI: 0.29-0.84, p = 0.009 < 0.05). Similarly, the four individual dominant species, Lactobacillus crispatus (OR = 0.3, 95% CI: 0.14-0.67, p = 0.003 < 0.05), Lactobacillus gasseri (OR = 0.34, 95% CI: 0.17-0.69, p = 0.003 < 0.05), Lactobacillus iners (OR = 0.68, 95% CI: 0.49-0.93, p = 0.016 < 0.05), and Lactobacillus jensenii (OR = 0.43, 95% CI: 0.21-0.89, p = 0.024 < 0.05), were also negatively associated with the PTB risk. The risk of Lactobacillus for PTB was significant in both America (OR = 0.67; 95% CI: 0.50-0.92) and Asia (OR = 0.20; 95% CI: 0.09-0.47), whereas no significant risk was found in Europe (OR = 0.49; 95% CI: 0.11-2.15). Conclusions: Our study demonstrated that the abundance of Lactobacillus and the four dominant individual species (L. crispatus, L. jensenii, L. iners, and L. gasseri) were significantly and negatively associated with the PTB risk.

INTRODUCTION AND HYPOTHESIS: Recurrent urinary tract infections (rUTIs) are a burden to patients and the health care economy. Vaginal probiotics and supplements have gained significant attention in mainstream media and lay press as a non-antibiotic alternative. We performed a systematic review to determine whether vaginal probiotics are an effective means of prophylaxis for rUTI. METHODS: A PubMed/MEDLINE article search was performed from inception to August 2022 for prospective, in vivo use of vaginal suppositories for the prevention of rUTIs. Search terms included: vaginal probiotic suppository (34 results), vaginal probiotic randomized (184 results), vaginal probiotic prevention (441 results), vaginal probiotic UTI (21 results), and vaginal probiotic urinary tract infection (91 results). A total of 771 article titles and abstracts were screened. RESULTS: A total of 8 articles fit the inclusion criteria and were reviewed and summarized. Four were randomized controlled trials, with 3 of the studies having a placebo arm. Three were prospective cohort studies, and 1 was a single arm, open label trial. Five of the 7 articles that specifically evaluated for rUTI reduction with vaginal suppositories did find a decreased incidence with probiotic use; however, only 2 had statistically significant results. Both of these were studies of Lactobacillus crispatus and were not randomized. Three studies demonstrated the efficacy and safety of Lactobacillus as a vaginal suppository. CONCLUSION: Current data support the use of vaginal suppositories containing Lactobacillus as a safe, non-antibiotic measure, but actual reduction of rUTI in susceptible women remains inconclusive. The appropriate dosing and duration of therapy remain unknown. © 2023. The Author(s).

Preterm birth is a major cause of neonatal morbidity and mortality worldwide. Increasing evidence links the vaginal microbiome to the risk of spontaneous preterm labour that leads to preterm birth. The aim of this systematic review and network meta-analysis was to investigate the association between the vaginal microbiome, defined as community state types (CSTs, i.e. dominance of specific lactobacilli spp, or not (low-lactobacilli)), and the risk of preterm birth. Systematic review using PubMed, Web of Science, Embase and Cochrane library was performed. Longitudinal studies using culture-independent methods categorizing the vaginal microbiome in at least three different CSTs to assess the risk of preterm birth were included. A (network) meta-analysis was conducted, presenting pooled odds ratios (OR) and 95% confidence intervals (CI); and weighted proportions and 95% CI. All 17 studies were published between 2014 and 2021 and included 38-539 pregnancies and 8-107 preterm births. Women presenting with "low-lactobacilli" vaginal microbiome were at increased risk (OR 1.69, 95% CI 1.15-2.49) for delivering preterm compared to Lactobacillus crispatus dominant women. Our network meta-analysis supports the microbiome being predictive of preterm birth, where low abundance of lactobacilli is associated with the highest risk, and L. crispatus dominance the lowest. © 2022. The Author(s).

The human microbiome plays a crucial role in determining the health status of every human being, and the microbiome of the genital tract can affect the fertility potential before and during assisted reproductive treatments (ARTs). This review aims to identify and appraise studies investigating the correlation of genital microbiome to infertility. Publications up to February 2021 were identified by searching the electronic databases PubMed/MEDLINE, Scopus and Embase and bibliographies. Only full-text original research articles written in English were considered eligible for analysis, whereas reviews, editorials, opinions or letters, case studies, conference papers, and abstracts were excluded. Twenty-six articles were identified. The oldest studies adopted the exclusive culture-based technique, while in recent years PCR and RNA sequencing based on 16S rRNA were the most used technique. Regardless of the anatomical site under investigation, the Lactobacillus-dominated flora seems to play a pivotal role in determining fertility, and in particular Lactobacillus crispatus showed a central role. Nonetheless, the presence of pathogens in the genital tract, such as Chlamydia trachomatis, Gardnerella vaginalis, Ureaplasma species, and Gram-negative stains microorganism, affected fertility also in case of asymptomatic bacterial vaginosis (BV). We failed to identify descriptive or comparative studies regarding tubal microbiome. The microbiome of the genital tract plays a pivotal role in fertility, also in case of ARTs. The standardization of the sampling methods and investigations approaches is warranted to stratify the fertility potential and its subsequent treatment. Prospective tubal microbiome studies are warranted.

BACKGROUND: Vaginal dysbiosis characterized by depleted lactobacilli is usually correlated with human papillomavirus (HPV) infection and cervical carcinogenesis, but the effect of the Lactobacillus genus and represented species on this process remains unclear. METHODS: PubMed, EMBASE, and CENTRAL databases were searched up to February 15, 2019. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using a fixed-effect model and Review Manager (version 5.3) for Mac. RESULTS: Eleven studies comprising 1230 cases were included. Lactobacillus spp. was associated with the decreased detection of high-risk subtype (hr)HPV infection (OR = 0.64, 95% CI = 0.48-0.87, I2 = 6%), cervical intraepithelial neoplasia (CIN) (OR = 0.53, 95% CI = 0.34-0.83, I2 = 0%), and cervical cancer (CC) (OR = 0.12, 95% CI = 0.04-0.36, I2 = 0%). At the level of Lactobacillus species, Lactobacillus crispatus, but not Lactobacillus iners, was correlated with the decreased detection of hrHPV infection (OR = 0.49, 95% CI = 0.31-0.79, I2 = 10%) and CIN (OR = 0.50, 95% CI = 0.29-0.88, I2 = 0%). CONCLUSIONS: Cervicovaginal Lactobacillus spp. is associated with the decreased detection of hrHPV infection, CIN, and CC; L. crispatus may be the critical protective factor. © The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: [email protected].

BACKGROUND: Persistent infection with high-risk human papillomavirus can lead to cervical dysplasia and cancer. Recent studies have suggested associations between the composition of the vaginal microbiota, infection with human papillomavirus (HPV) and progression to cervical dysplasia and cancer. OBJECTIVE: To assess how specific cervico-vaginal microbiota compositions are associated with HPV infection, cervical dysplasia and cancer, we conducted a systematic review and network meta-analysis (registered in PROSPERO: CRD42018112862). SEARCH STRATEGY: PubMed, Web of science, Embase and Cochrane database. SELECTION CRITERIA: All original studies describing at least two community state types of bacteria (CST), based on molecular techniques enabling identification of bacteria, and reporting the association with HPV infection, cervical dysplasia and/or cervical cancer. DATA COLLECTION AND ANALYSIS: For the meta-analysis, a network map was constructed to provide an overview of the network relationships and to assess how many studies provided direct evidence for the different vaginal microbiota compositions and HPV, cervical dysplasia or cancer. Thereafter, the consistency of the model was assessed, and forest plots were constructed to pool and summarise the available evidence, presenting odds ratios and 95% confidence intervals. MAIN RESULTS: Vaginal microbiota dominated by non-Lactobacilli species or Lactobacillus iners were associated with three to five times higher odds of any prevalent HPV and two to three times higher for high-risk HPV and dysplasia/cervical cancer compared with Lactobacillus crispatus. CONCLUSIONS: These findings suggest an association between certain bacterial community types of the vaginal microbiota and HPV infection and HPV-related disease. This may be useful for guiding treatment options or serve as biomarkers for HPV-related disease. TWEETABLE ABSTRACT: This network meta-analysis suggests an association between different vaginal bacterial community types and the risk of HPV. © 2019 Royal College of Obstetricians and Gynaecologists.