vesicoureteral reflux, L. acidophilus treatment daily was as effective as trimethoprim/sulfamethoxazole in reducing

four intravaginal products. Patients were diagnosed with BV if ≥3 Amsel criteria were present. Each of the four Supernatant of Lactobacillus inhibits cervical cancer cells by regulating HPV oncogenes and cell cycle related genes. with myeloperoxidase and chloride in vaginal mucus, to be toxic toward G. vaginalis, with a maximum toxicity in a pH range of 5 to 6. A pH of ≤4.5 inhibited the growth of G. vaginalis on its own and this effect Gordillo Altamirano, F. L. & Barr, J. J. Phage therapy in the postantibiotic Era. Clin Microbiol Rev.s 32, e00066–18 (2019).and L. reuteri RC-14 at 1.0 × 10 9 colony-forming units ( n = 65) for a total treatment duration of 30 days. At the estrogen and progesterone HRT, only 1 to 3 species of bacteria, mainly Lactobacillus, were detected in the vaginal Verstraelen, H. et al. Longitudinal analysis of the vaginal microflora in pregnancy suggests that L. crispatus promotes the stability of the normal vaginal microflora and that L. gasseri and/or L. iners are more conducive to the occurrence of abnormal vaginal microflora. BMC Microbiol. 9, 116 (2009). Patients who received cisplatin and pelvic radiotherapy were divided into a probiotic group and a placebo group.

BV prevalence varies geographically and ethnically, and can affect >50% of women in some countries 6. BV is diagnosed using Amsel’s criteria or Nugent score, with Amsel’s criteria more commonly used in the clinic 5. Amsel’s criteria combines inspection of vaginal secretions, pH measurement, visual inspection under microscopy, and the Whiff test, whereas the Nugent score focuses exclusively on scoring Gram-stained microscopy images. The BV definition based on DNA sequencing of vaginal secretions is referred to as molecular BV 7, 8. Hans, V. & Rita, V. Bacterial vaginosis: an update on diagnosis and treatment. Expert Rev. Anti Infect. Ther. 7, 1109–1124 (2009). endocarditis, and localized infections associated with Lactobacillus that were investigated by Cannon et al. were considered to have a Lactobacillus monoisolate or mixtures of healthy vaginal bacterial strains, with combinations of beneficial molecules, could be additional options for treatment 72. Another promising approach currently in clinical trial is the Flourish Vaginal Care System (ClinicalTrials.gov, Identifier: NCT03734523) 90, which includes bio-matched vaginal secretions of women with L. crispatus-dominated microbiome, a probiotic combination of L. crispatus and other strains, and a gentle, pH-balancing cleanser. All of these methods including a probiotic mix, prebiotic combinations, and/or bacteriophages provide more controlled conditions, convenience for clinical application, and ease of commercialization compared to VMT. Challenges/opportunity of treating BV using novel interventions including probiotics and VMT Patients were randomized to a probiotics group (containing 75 billion live freeze-dried bacteria) or a placebo group.Women who used pessaries were randomized to vaginal probiotic suppository use versus without use. The intervention was a vaginal probiotic suppository and moisturizing vaginal gel. The vaginal microenvironment was assessed using Gram stain and Nugent's criteria at baseline and 3 months by a microbiologist blinded to group allocation. Symptoms and experience with use of the probiotic were assessed using questionnaires. The primary outcome was change in lactobacilli count on Nugent subscore at 3 months. DI Pierro F., Criscuolo A. A., Dei Giudici A., Senatori R., Sesti F., Ciotti M., et al.. (2021). Oral administration of lactobacillus crispatus M247 to papillomavirus-infected women: results of a preliminary, uncontrolled, open trial. Minerva Obstet Gynecol 73 ( 5), 621–631. doi: 10.23736/s2724-606x.21.04752-7 Overall, VMT presents a promising way to combine antibiotic treatment and restoration of the vaginal microbiome to combat vaginosis-related bacteria. It also provides a whole environment, including the mixture of vaginal microbes and molecules produced by both hosts and microbes (e.g., lactic acid, cytokines, bacteriocins, and antimicrobial peptides), which assists in the colonization of essential bacteria while working against BV-associated bacteria 9, 11, 14. These molecules might be essential for the successful re-establishment of a healthy vaginal microbiome. Bisanz, J. E. et al. A systems biology approach investigating the effect of probiotics on the vaginal microbiome and host responses in a double blind, placebo-controlled clinical trial of post-menopausal women. PLoS One 9, e104511 (2014). De Seta F, Parazzini F, De Leo R et al. Lactobacillus plantarum P17630 for preventing Candida vaginitis recurrence: a retrospective comparative study. Eur J Obstet Gynecol Reprod Biol 2014;182:136-9.

Chao X. P., Sun T. T., Wang S., Fan Q. B., Shi H. H., Zhu L., et al.. (2019). Correlation between the diversity of vaginal microbiota and the risk of high-risk human papillomavirus infection. Int. J. Gynecol Cancer 29 ( 1), 28–34. doi: 10.1136/ijgc-2018-000032 After completing metronidazole treatment, patients received placebo and yogurt with probiotics, respectively (n=36). Despite the growing clinical evidence, the efficacy of probiotic treatment on BV remains controversial [ 16, 17, 18]. Up to now, three meta-analyses have been reported [ 19, 20, 21], but none of them has explored the sources of interpretable heterogeneity and its influence on the results. One of them was published in 2009 in the Cochrane Library with only four studies. Another meta-analysis by Huang and colleagues exhibited a considerable heterogeneity ( I 2 = 87%) of the effect with no further explanations. The latest one, by Tan et al., only focused on the impact of probiotics as a supplementary therapy with metronidazole and attributed the heterogeneity ( I 2 = 83%) to one single study (the I 2 was reduced to 16% after omission of this single study) without further explanations. Thus, a widely accepted consensus has not been formulated yet.

Bradshaw, C. S. et al. Efficacy of oral metronidazole with vaginal clindamycin or vaginal probiotic for bacterial vaginosis: randomised placebo-controlled double-blind trial. PLoS One 7, e34540 (2012).

Lactobacillus crispatus LbV 88, Lactobacillus gasseri LbV 150N, Lactobacillus jensenii LbV 116 and Lactobacillus rhamnosus LbV96 After completing metronidazole treatment, patients received placebo and vaginal tablets containing probiotics, respectively (n=250).The advantages of treatment with antibiotics are their availability and convenience for clinical use. Patients can easily administer antibiotics at home with instruction. Also, since BV is characterized by the overgrowth of anaerobic bacteria, reduced vaginal bacterial load following antibiotic treatment may provide the chance for Lactobacillus species to compete for nutrients and biological niches again. Overall, a large proportion of women with BV have been cured after one-time treatment in a short period of time 27, 33, 34.