Wrønding Tine, Vomstein Kilian, Bosma Elleke F, Mortensen Brynjulf, Westh Henrik, Heintz Julie Elm, Mollerup Sarah, Petersen Andreas Munk, Ensign Laura M, DeLong Kevin, van Hylckama Vlieg Johan E T, Thomsen Anne Bloch, Nielsen Henriette Svarre
Department of Obstetrics and Gynecology, The Fertility Clinic, Hvidovre University Hospital, Copenhagen, Denmark.
Freya Biosciences Aps, Copenhagen, Denmark.
EClinicalMedicine. 2023 Jun 26;61:102070. doi: 10.1016/j.eclinm.2023.102070. eCollection 2023 Jul.
Vaginal dysbiosis covers imbalances in the vaginal microbiota, defined by altered composition of bacteria, viruses, and fungi and is associated with euploid pregnancy losses, premature birth, infertility, or bacterial vaginosis. A large proportion of women who have vaginal dysbiosis do not experience any symptoms. Antibiotics are the traditional treatment, recently combined with local probiotics in some cases. Vaginal Microbiota Transplantation (VMT) with eubiotic vaginal bacterial microbiota after antibiotic eradication of pathogens has successfully been performed in a case study with five patients, but no VMT has been performed without the use of antibiotics.
This is a proof of concept case study. The patient was found to have vaginal dysbiosis at the RPL clinic at Copenhagen University Hospital Hvidovre, Denmark on the 23rd of June 2021. She was offered and accepted to receive experimental treatment in the form of a VMT as a compassionate use case. VMT is the transfer of cervicovaginal secretions (CVS) from a healthy donor with a -dominant vaginal microbiome to a recipient with a dysbiotic vaginal microbiome. CVS is a mixture of e.g., mucus, bacteria, metabolites present in the vaginal canal. Potential donors were thoroughly screened for the absence of STIs, and the most suitable donor sample for the specific patient in this study was determined via an in vitro microbiome competition assay.
A 30-year-old patient with one livebirth and a complicated pregnancy history of two stillbirths and 1 s trimester pregnancy loss in gestational weeks 27 (2019), 17 (2020) and 23 (2020) respectively with complaints of vaginal irritation and discharge that had aggravated in all her pregnancies. Her vaginal microbiome composition showed a 90% dominance of spp. After one VMT there was a complete shift in microbiome composition to 81.2% and 9% with a concurrent resolvement of vaginal symptoms. Single nucleotide polymorphism-analysis confirmed her microbiome to be of donor origin and it remain stable now 1.5 years after the VMT. Five months after the VMT she became pregnant and has successfully delivered a healthy baby at term.
Here we report a successful VMT with confirmed donor strain engraftment followed by a successful pregnancy and delivery after a series of late pregnancy losses/stillbirths. Findings suggest that VMT is a potential treatment for severe vaginal dysbiosis. Further, larger studies are required.
The study was partially funded (i.e., analysis costs) by Freya Biosciences Aps, Fruebjergvej, 2100 Copenhagen, Denmark.
阴道微生物群失调涵盖阴道微生物群的失衡，其定义为细菌、病毒和真菌组成的改变，与整倍体妊娠丢失、早产、不孕或细菌性阴道病有关。很大一部分有阴道微生物群失调的女性没有任何症状。抗生素是传统治疗方法，最近在某些情况下会联合局部益生菌使用。在一项针对五名患者的案例研究中，在抗生素根除病原体后，成功进行了用健康阴道细菌微生物群进行的阴道微生物群移植（VMT），但尚未在未使用抗生素的情况下进行VMT。
这是一项概念验证案例研究。2021年6月23日，在丹麦哥本哈根大学医院Hvidovre的复发性流产诊所发现该患者存在阴道微生物群失调。作为一个同情用药案例，她被提供并接受了以VMT形式的实验性治疗。VMT是将具有优势阴道微生物群的健康供体的宫颈阴道分泌物（CVS）转移到阴道微生物群失调的受体。CVS是阴道管中存在的例如黏液、细菌、代谢物的混合物。对潜在供体进行了彻底筛查以排除性传播感染，并且通过体外微生物群竞争试验确定了本研究中特定患者的最合适供体样本。
一名30岁患者，有一次活产，有复杂的妊娠史，分别在妊娠27周（2019年）、17周（2020年）和23周（2020年）有两次死产和一次孕早期妊娠丢失，主诉阴道刺激和分泌物增多，在她所有妊娠中均加重。她的阴道微生物群组成显示 菌属占90%。一次VMT后，微生物群组成完全转变为81.2% 和9% ，同时阴道症状得到缓解。单核苷酸多态性分析证实她的微生物群来自供体，并且在VMT后1.5年仍然稳定。VMT五个月后她怀孕并足月成功分娩了一个健康婴儿。
在此我们报告了一次成功的VMT，供体菌株植入得到证实，随后在一系列晚期妊娠丢失/死产后成功妊娠并分娩。研究结果表明VMT是严重阴道微生物群失调的一种潜在治疗方法。此外，需要进一步开展更大规模的研究。
该研究部分由Freya Biosciences Aps资助（即分析成本），地址为丹麦哥本哈根2100弗勒比约格韦街。
