Vaginal Microbiome Transplantation for Recurrent Bacterial Vaginosis

Bacterial Vaginoses

Vaginal Microbiome Transplantation (VMT) may be beneficial in treating the most severe cases of recurrent and antibiotics-nonresponsive cases of BV. We completed a preliminary study in which we treated patients with recurrent and antibiotics-non-responsive, intractable BV, with VMT from healthy donors \[Lev-Sagie, Nature Medicine 2019\]. Four VMT recipients in this preliminary study featured a significant improvement of both clinical symptoms and dysbiotic vaginal microbiome composition and function, which persisted over a long follow-up period, while one recipient featured a partial remission. The proposed study is designed as a placebo, randomized controlled trial, and is aimed to further assess whether VMT may serve as a viable option in symptomatic, intractable BV. In the suggested study, we compare transplantation of: 1) vaginal fluid from healthy donors (VMT), and 2) saline and glycerol (placebo).

Women diagnosed with symptomatic, recurrent BV, will be recruited. After assessment of inclusion and exclusion criteria and patient's consent to participate, patients will be assigned to receive transplantation of either VMT or a placebo. Patients will be blinded to the therapy given. Following VMT, patients will be examined every 2 weeks for the first month, and then once every month, for additional 11 months after VMT. In case of BV recurrence, repeated transplantations will be done after antibiotics. Repeated VMTs can be done to a maximum of 6 sessions, before the procedure will be considered a failure. Placebo recipients will be examined every 2 weeks for the first month, and then once every month for additional 3 months after placebo (total of 4 months). Patients may have up to 3 repeated placebo transplantations during the 4 months. At the 4 months post placebo timepoint, in case they are still symptomatic and fulfill inclusion criteria, patients who initially received placebo will be unblinded and offered a VMT. After VMT, they will be further followed for additional 12 months (every two weeks for the first month and then once a month for additional 11 months). In each frontal appointment: 1. Patients will be questioned regarding symptoms (discharge and odor) , adverse events (related and not related to the study), and compliance with the protocol. 2. Will undergo examination which will include vaginal inspection, pH measurement, whiff test and microscopy. 3. Samples will be taken. During the follow-up phase, women who are clinically stable and asymptomatic will be given the option to collect a monthly vaginal sample at home, store it in their home freezer, and bring the collected samples to the clinic at three-month intervals when they arrive to their examination visit. These women will be contacted monthly and will be asked about their symptoms. If they report any change in their condition or recurrence of symptoms, they will be asked to attend the clinic for an examination. In order to prevent transfer of pathogens, sperm, or antibiotic-resistant commensals we will establish a "vaginal fluid bank" in which samples from suitable donors will be kept for future use: * Donors will be screened using a questionnaire addressing risk factors for potentially transmissible infections, undergo screening for cervico-vaginal infections, cervical cytology screening, and serology analysis for transmittable infections. * The collected samples for VMT will be examined for bacteria,viruses and sperm. * Each sample will be sequenced to verify its composition (L. crisptus dominance). * Three months after collection of a sample, donors will undergo repeated serologic screening, to verify for the absence of sero-conversion prior to VMT. In addition to the main cohort, we will conduct additional observational study;To assess the antimicrobial effects of lactobacilli on pathogenic bacteria, we will use 100 fresh samples from patients with BV or healthy controls. 100ul of These samples will be cultured to evaluate the influence of three antimicrobial molecules secreted by lactobacilli on both pathogenic bacteria and beneficial Lactobacilli in the vaginal microbiome. As a control, we will use lactic acid or boric acid. Samples will be analysed for the microbiome composition before culturting, after over-night culturing and after treatment with the antimicrobial molecules.

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