Vaginal microbiome transplantation in women with intractable bacterial vaginosis

Abstract

We report the results of a first exploratory study testing the use of vaginal microbiome transplantation (VMT) from healthy donors as a therapeutic alternative for patients suffering from symptomatic, intractable and recurrent bacterial vaginosis (ClinicalTrials.gov NCT02236429). In our case series, five patients were treated, and in four of them VMT was associated with full long-term remission until the end of follow-up at 5-21 months after VMT, defined as marked improvement of symptoms, Amsel criteria, microscopic vaginal fluid appearance and reconstitution of a Lactobacillus-dominated vaginal microbiome. One patient presented with incomplete remission in clinical and laboratory features. No adverse effects were observed in any of the five women. Notably, remission in three patients necessitated repeated VMT, including a donor change in one patient, to elicit a long-standing clinical response. The therapeutic efficacy of VMT in women with intractable and recurrent bacterial vaginosis should be further determined in randomized, placebo-controlled clinical trials.Bacterial vaginosis (BV) is a form of vaginal microbial community alteration in which the microbiome normally dominated by Lactobacillus species switches to one characterized by the emergence of anaerobes [1][2][3][4] . BV is prevalent in women of reproductive age, affecting from one-fourth to one-third of women 5 . It ranges from an asymptomatic finding in most cases to a clinically symptomatic entity characterized by an abnormal, often malodorous vaginal discharge in 16% of women diagnosed with BV, summing up to a prevalence of 4.4% for symptomatic BV in women aged 14-49 years 5 . BV may be associated with risk of upper genital tract infection 6 , complications of pregnancy (particularly preterm birth and lower success in fertility treatments [7][8][9][10] ) and susceptibility to sexually transmitted infections 11 . At the clinically severe end of the BV spectrum, treatment with antibiotics (either systemic or vaginal) is associated with a 30% relapse rate within 3 months of initial treatment and a relapse rate of up to 50-70% within 1 year 12 . Therapeutic options are very limited in the subpopulation of women who experience persistent or recurrent BV despite multiple antibiotic treatment attempts [13][14][15] . Maintenance antimicrobial treatment 16,17 is often the treatment suggested in these cases, but it can predispose to vaginal candidiasis 18 and resistant infections 19,20 . Importantly, probiotic treatment of symptomatic patients with oral and/or vaginal administration of bacterial Lactobacillus strains has produced mixed results 21,22 , suggesting that the microbiome as a whole, rather than a single bacterial species, may be necessary for an effective cure at the clinically

The Role of the Cervicovaginal Microbiome on the Genesis and as a Biomarker of Premalignant Cervical Intraepithelial Neoplasia and Invasive Cervical Cancer

“…In addition to mother-to-infant transplantation, VMT has been recently evaluated as a treatment option for patients with recurrent BV after being subjected to different antimicrobial regimens [154]. Vaginal fluid was collected from healthy donors to test its potential therapeutic effects in five patients with relapsing BV.…”

“…The post-VMT microbiota was characterized by an increase in Lactobacillus species coupled with a simultaneous decrease in members of Bifidobacterium, Prevotella, and other genera. Interestingly, three patients required repeated VMT (and even a donor change for one of them) to reach BV remission [154], suggesting that the VMT dosage and possible donor-recipient specifications are still to be determined with confidence.…”

Cervicovaginal microbiome composition drives metabolic profiles in healthy pregnancy

“…The vaginal communities were characterized by a high abundance of one or a few acid-tolerant species, which dictated the physiologic potential and the metabolic profiles of the vaginal microbiome. Many of the metabolites that were specific to these different organisms warrant further investigation, especially considering the recent development of VMT as a treatment for BV [28]. The metabolites we found to be associated with L. crispatus may be useful as microbiome cultivation approaches are developed to intentionally direct the composition of the vaginal microbiome.…”

“…Bacterial vaginosis (BV), the most common gynecological condition in reproductive aged women [20], is characterized by the presence of a more diverse vaginal microbiome and associated with adverse pregnancy outcomes including preterm birth [21], endometritis [22, 23] and spontaneous abortion [24–27]. Recently, vaginal microbial transplants have been successfully implemented as a treatment for intractable BV [28]. Despite L. crispatus generally being regarded as a highly beneficial and dominant microbe throughout pregnancy, healthy women from different ethnic groups have markedly different species dominating the vaginal microbiome [15].…”

Personalized vagino-cervical microbiome dynamics after oral probiotics

“…Other factors such as hormonal dynamics 24 , seasonal changes 25 may also have influenced our study. Recent studies of vaginal microbial transplant (VMT) and treatment of BV using L. crispatus have all used a more direct topical application after standard metronidazole treatment 26,27 . Yet, oral probiotics are more readily consumed in a subclinical setting, and may be more acceptible for pregnant women with a risk for preterm birth.…”