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ARTICLE

Vaginal Microbiome Transplantation Effective in Intractable Bacterial Vaginosis

DEC 09, 2019 | UMIDA NASRITDINOVA, PHARMD CANDIDATE; KIRK E. HEVENER, PHARMD, PHD*
Microbiome transplantation has been a controversial topic since the introduction of fecal microbiome transplantation (FMT) for the treatment of recurrent Clostridioides difficile infections. While this treatment modality may be considered unconventional, multiple FMT trials have reported favorable outcomes, with some studies showing up to 100% C difficile cure rates (Table 1).1-4 Four-year follow-up studies of FMT-treated patients showed significantly improved bowel habits and decreased gastrointestinal tract symptoms compared to antibiotic therapy, which indicates that the long-term effects can prove to be beneficial.5 Given the reported efficacy and safety profile of FMT, researchers have begun investigating a potential role for the procedure in the management of other disease states believed to be affected by the microbiome, including inflammatory bowel disease and depression.6-7 A natural progression in the research of microbiome transplantation for the treatment and prevention of chronic disease is to study the role of microbiome transplantation at other sites of human colonization. A recent study by Lev-Sagie and colleagues reported the benefit of vaginal microbiome transplantation (VMT) for the treatment of recurrent bacterial vaginosis (BV).8 Their results are striking and are likely to spur a significant amount of further research in this area.


The authors reported a prospective, non-randomized trial of 5 women with intractable BV, defined as having high relapse of symptoms and overall negative impact on patients’ quality of life. The subjects were given VMTs from healthy donors and evaluated for improvement in symptoms. Before the transplantation, all patients were treated with an intravaginal antibiotic regimen that previously allowed symptom-free intervals. The process of the transplantation included transferring vaginal fluids collected from healthy donors’ vaginal fornices to the patients with intractable BV. The patients had weekly follow-up appointments for the first month, during which remission was defined as having disappearance of symptoms, normalization of all Amsel criteria,9 and the reconstitution of a normal Lactobacillus-dominated vaginal microbiome. Patients A and B were reported to have immediate improvement after a single transplant. Patient C and D were reported to have microscopic findings consistent with BV and a recurrence of symptoms, respectively; however, after another VMT trial, they were able to achieve full remission. Patient E was reported to have a partial symptomatic improvement after a second VMT procedure. No adverse events were reported for any of the 5 patients.  

While VMT appears to be a promising potential treatment option for women who suffer from refractory bacterial vaginosis, the study was limited by the low number of recruited patients, patient-physician blinding, and randomization; therefore, its applicability to general practice is still uncertain. Follow-up studies with greater numbers of patients and placebo controls should be performed to assess the full efficacy of this treatment. Future studies should also assess potential risks, including transmission of multidrug-resistant pathogens, induction of other diseases, and long-term side effects. Notwithstanding this, the findings of this study are of strong clinical interest because they suggest a potential avenue for BV treatment in patients who have exhausted other medical and pharmacologic options. The potential impact is significant as bacterial vaginosis affects nearly 30% of the female population every year.10  Of the 21.2 million affected women, a subset further develops recurrent disease, which typically requires chronic antibiotic suppressive therapy, further driving high relapse rates. This study by Lev-Sagie and colleagues shows that microbiome transplantation is a promising frontier in treating intractable bacterial vaginosis by targeting the root cause, a dysbiosis which leads to eruption of disease. Of the 5 patients who suffered from the negative impacts of recurrent disease, 4 patients achieved full remission with no pharmacologic interventions after the transplant. More importantly, none of the patients experienced side effects. This procedure may offer a potential therapeutic alternative to safeguard patients from chronic antibiotic use and its sequalae, particularly in the era where multi-drug resistant pathogens are becoming more common.

Microbiome transplantation presents an attractive treatment option for chronic and recurrent infections such as C difficile and bacterial vaginosis. Furthermore, this study suggests that VMT may be applied to other recurrent infections which are the result of a dysregulated microbiome, such as chronic yeast or urinary tract infections and also a potential role for microbiome transplantation in other areas of human colonization associated with chronic infection such as the oral cavity and the skin.
Nasritdinova is a current third-year student at UTHSC College of Pharmacy in Nashville, TN. Her clinical interests include critical care, infectious diseases, and public health, particularly in underserved populations.

Hevener is an assistant professor of pharmaceutical sciences at University of Tennessee College of Pharmacy. His research focuses on the characterization and validation of narrow-spectrum antibacterial drug targets. He is a member of Contagion®’s Editorial Advisory Board. He is also an active member of the Society of Infectious Diseases Pharmacists.

References
  1. Kelly CR, Khoruts A, Staley, C, et al. Effect of fecal microbiota transplantation on recurrence in multiply recurrent Clostridium difficile infection: A randomized trial. Ann Intern Med. 2016, 165 (9), 609-616.  doi: 10.7326/M16-027
  2. Youngster I, Mahabamunuge J, Systrom HK, et al. Oral, frozen fecal microbiota transplant (FMT) capsules for recurrent Clostridium difficile infection. BMC Med. 2016 Sep 9;14 (1), 134. doi: 10.1186/s12916-016-0680-9.
  3. Jiang ZD, Ajami NJ, Petrosino, JF, et al. Randomised clinical trial: Faecal microbiota transplantation for recurrent Clostridum difficile infection - fresh, or frozen, or lyophilised microbiota from a small pool of healthy donors delivered by colonoscopy. Aliment Pharmacol Ther. 2017 Apr;45 (7), 899-908. doi: 10.1111/apt.13969.
  4. Myles IA, Earland NJ, Anderson ED, First-in-human topical microbiome transplantation with roseomonas mucosa for atopic dermatitis. JCI Insight 2018 May 3;3 (9). pii: 120608. doi: 10.1172/jci.insight.120608.
  5. Jalanka J, Hillamaa A, Satokari R, Mattila E, Anttila VJ, Arkkila P. The long-term effects of faecal microbiota transplantation for gastrointestinal symptoms and general health in patients with recurrent Clostridium difficile infection. Aliment Pharmacol Ther. 2018 Feb;47 (3), 371-379. doi: 10.1111/apt.14443. 
  6. Levy, A. N.; Allegretti, J. R., Insights into the role of fecal microbiota transplantation for the treatment of inflammatory bowel disease. Therap Adv Gastroenterol. 2019 Mar, 12, 1756284819836893. doi: 10.1177/1756284819836893.
  7. NCT03281044. Fecal Microbiota Transplantation in Depression. Clinical Trials.gov website. https://clinicaltrials.gov/ct2/show/NCT03281044. Accessed December 3, 2019.
  8. Lev-Sagie A, Goldman-Wohl D, Cohen Y, et al. Vaginal microbiome transplantation in women with intractable bacterial vaginosis. Nat Med. 2019 Oct, 25 (10), 1500-1504.  doi: 10.1038/s41591-019-0600-6. 
  9. Amsel R, Totten PA, Spiegel CA, Chen KC, Eschenbach D, Holmes KK. Nonspecific vaginitis. Diagnostic criteria and microbial and epidemiologic associations. Am J Med. 1983 Jan; 74 (1), 14-22. doi: 10.1016/00002-9343)83)911112-9.
  10. Koumans EH, Sternberg M, Bruce C, et al. The prevalence of bacterial vaginosis in the United States, 2001-2004; associations with symptoms, sexual behaviors, and reproductive health. Sex Transm Dis. 2007 Nov;34 (11), 864-9. Doi: 10.1097/OLQ.0b013e318074e565.
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