A total of 147 postmenopausal women were randomized (86 to the intervention arm and 61 to the control arm), and 124 (87.9%) presented for a 3-month follow-up. There was no difference between the arms in age, race, body mass index, and Charlson Comorbidity Index. A majority of participants had the pessary managed by the health care professional (intervention arm vs control arm, 46 [76.7%] vs 55 [68.8%]; P = 0.30). Composition of the vaginal microenvironment did not differ with or without probiotic treatment at 3 months. Bother from vaginal symptoms, including discharge, itching, and discomfort, did not differ between arms. Adverse effects from the intervention were minor, resolved with discontinuation, and occurred at 39.1%. Ma, Y., Chen, H., Lan, C. & Ren, J. Help, hope and hype: ethical considerations of human microbiome research and applications. Protein Cell 9, 404–415 (2018). Muzny, C. A. et al. An updated conceptual model on the pathogenesis of bacterial vaginosis. J. Infect. Dis. 220, 1399–1405 (2019).

Sexual Health and Wellness Institute. Clinical Trial to Survey Results of Flourish Vaginal Care System for Recurrent Bacterial Vaginosis. https://clinicaltrials.gov/ct2/show/NCT03734523 (2021).Hallén, A., Jarstrand, C. & Påhlson, C. Treatment of bacterial vaginosis with lactobacilli. Sex. Transm. Dis. 19, 146–148 (1992). Ehrström, S. et al. Lactic acid bacteria colonization and clinical outcome after probiotic supplementation in conventionally treated bacterial vaginosis and vulvovaginal candidiasis. Microbes Infect. 12, 691–699 (2010). Reid, G. et al. Oral use of Lactobacillus rhamnosus GR-1 and L. fermentum RC-14 significantly alters vaginal flora: randomized, placebo-controlled trial in 64 healthy women. FEMS Immunol. Med. Microbiol. 35, 131–134 (2003). Marcone, V., Calzolari, E. & Bertini, M. Effectiveness of vaginal administration of Lactobacillus rhamnosus following conventional metronidazole therapy: how to lower the rate of bacterial vaginosis recurrences. N. Microbiol 31, 429–433 (2008).

Puebla-Barragan, S. & Reid, G. Probiotics in cosmetic and personal care products: trends and challenges. Molecules 26, 1249 (2021). P. et al. Features of the cervicovaginal microenvironment drive cancer biomarker signatures in patients across cervical carcinogenesis. Sci. Rep. 9, 7333 (2019). Finally, the vaginal microenvironment is altered by BV-related bacteria, which could increase the difficulty for probiotic strains to compete with BV-related bacteria and hinder the colonization of probiotic strains 52. Thus, it may be necessary to open a niche for probiotic strains to minimize colonization resistance from resident bacteria, especially overgrown biofilm-forming bacteria. Combinations of antibiotics and probiotic treatments have been previously attempted. A study indicated that the combination of probiotics and metronidazole is more effective than antibiotics alone in maintaining a healthy vaginal ecosystem 67. There is also an overall higher remission rate with clinical trials with combined probiotic and antibiotic treatment (42–83%) compared to those using probiotics alone (20–48%) in long-term studies (≥4 months) (Table 4 vs. Table 2). For instance, short-term studies (<4 months) on L. rhamnosus GR-1 and L. reuteri RC-14 showed an 88% cure rate with antibiotic pretreatment compared to 51–88% in L. rhamnosus GR-1 and L. reuteri RC-14 only without antibiotic pretreatment (Tables 1 and 3) 55, 56, 58. Moreover, long-term studies (≥4 months) on L. rhamnosus GR-1 and L. reuteri RC-14 showed a 42% cure rate with antibiotic pretreatment compared to 20% on L. rhamnosus GR-1 and L. reuteri RC-14 only without antibiotic pretreatment 59, 60 (Tables 2 and 4). Given that orally administered antibiotics influence the whole gut microbiome 36, 37, we propose larger randomized cohort studies with L. crispatus delivered directly to the vagina after pretreatment with antibiotics administered vaginally that reduce the influence of BV-related bacteria (Fig. 1). VMT Bohbot, J. M. et al. Efficacy and safety of vaginally administered lyophilized Lactobacillus crispatus IP 174178 in the prevention of bacterial vaginosis recurrence. J. Gynecol. Obstet. Hum. Reprod. 47, 81–86 (2018).

susceptible to UTI, it was discovered that immunological defects in peripheral blood coexisted with a persistently Eligibility criteria were based on the PICOS framework [ 23]: (1) premenopausal nonpregnant women with BV were enrolled (BV was defined by one of three diagnostic tests recommended by widely accepted clinical guidelines [ 24, 25], namely Nugent score [ 26], Amsel criteria [ 27] or Hay/Ison criteria [ 28]); (2) probiotic preparations, single or mixed strains with any dosage, route of administration and preparation types (including capsules, tablets, tampons, pessaries, and effervescent tablets); (3) control arm used placebo or active controls (with an active ingredient including metronidazole, tinidazole, and clindamycin); (4) the outcomes of interest were reported (see Section 2.3); (5) randomized, double- or triple-blind controlled trials with follow-up of at least one menstrual cycle (verification time of BV cure according to guidelines from the FDA [ 29]). Latham-Cork, H. C. et al. A novel non-antimicrobial treatment of bacterial vaginosis: An open label two-private centre study. Eur. J. Obstet. Gynecol. Reprod. Biol. 256, 419–424 (2021). Meriwether KV, Rogers RG, Craig E, et al. The effect of hydroxyquinoline-based gel on pessary-associated bacterial vaginosis: a multicenter randomized controlled trial. Am J Obstet Gynecol. 2015;213(5):729.e1–729.e9. doi:10.1016/j.ajog.2015.04.032. estrogen and progesterone HRT, only 1 to 3 species of bacteria, mainly Lactobacillus, were detected in the vaginal

Das S., Bhattacharjee M. J., Mukherjee A. K., Khan M. R. (2022). Recent advances in understanding of multifaceted changes in the vaginal microenvironment: implications in vaginal health and therapeutics. Crit. Rev. Microbiol. 21, 1–27. doi: 10.1080/1040841x.2022.2049696 Pan, M., Hidalgo-Cantabrana, C., Goh, Y. J., Sanozky-Dawes, R. & Barrangou, R. Comparative analysis of Lactobacillus gasseri and Lactobacillus crispatus isolated from human urogenital and gastrointestinal tracts. Front. Microbiol. 10, 3146 (2020). Ravel, J. et al. Vaginal microbiome of reproductive-age women. Proc. Natl. Acad. Sci. USA 108, 4680–4687 (2011).five days. They either inserted an intravaginal capsule with L. rhamnosus GR-1 and L. reuteri RC-14 at 1.0 × 10 9 colony-forming reduced the bacteriostatic effects of L. acidophilus on G. vaginalis NCTC 11292 by 60%; a 30% reduction in bacteriostatic effects was seen when Patients were randomized to a probiotics group (containing 75 billion live freeze-dried bacteria) or a placebo group. Russo, R. & Karadja, E. & De Seta, F. Evidence-based mixture containing Lactobacillus strains and lactoferrin to prevent recurrent bacterial vaginosis: a double blind, placebo controlled, randomised clinical trial. Benef. Microbes 10, 19–26 (2019).