阴道菌群移植对细菌性阴道感染疾病治疗作用的初步研究

发布时间：2018-06-25 14:04

本文选题：粪菌移植 + 阴道菌群　；参考：《南昌大学》2017年硕士论文

【摘要】：细菌性阴道病(Bacterial Vaginosis,BV)是一类由阴道微生态环境失调导致的妇科炎症,常伴有盆腔炎、子宫内膜炎和不孕不育等并发症。作为阴道内重要的功能菌群,乳酸菌在维持阴道内环境稳态的过程中发挥着重要作用,其数量下降会导致阴道pH值上升、酸性减弱,进而造成阴道加德纳菌、类杆菌等常见致病病原体大量增殖,造成不同程度的妇科炎症。目前,抗生素仍是阴道妇科疾病的主要治疗手段,但抗生素的滥用常可导致宿主对抗生素的耐药及对阴道正常功能菌群的破坏,致使阴道微生态环境进一步失衡,妇科疾病易复发且不易根治的局面。鉴于粪菌移植技术在调节肠道菌群方面的良好效果,本研究团队首次提出阴道菌群移植的概念,即将健康宿主阴道分泌液中获取的阴道菌群移植到患有细菌性阴道感染疾病的女性阴道中,达到重建患者阴道菌群微生态平衡,促进其阴道内环境的恢复、抑制致病菌的增殖,同时从根本上实现治疗阴道妇科疾病的目的。本课题以细菌性阴道感染大鼠模型为研究对象,评价了阴道菌群移植技术对其的治疗效果。研究结果表明,从健康大鼠收集到的阴道分泌物含总菌数约为105 CFU/mL,其中乳酸菌含量约为104 CFU/m L,占总菌数的7.8%。高通量测序结果表明,实验共得到622个OTUs,平均每组样品含有103个OTUs;属水平的聚类分析结果表明,阴道菌群主要由凝聚杆菌属(Aggregatibacter)、拟杆菌属(Bacteroides)、链杆菌属(Streptobacillus)、梭菌属(Fusobacterium)和卟啉单胞菌属(Porphyromonas)构成,其中优势凝聚杆菌属(Aggregatibacter)在对照组(C组)占48.17%、模型组(M组)占59.37%、模型组治疗期(M.M组)占27.06%、模型组恢复期(M.R组)占48.92%、治疗组治疗期(T.M组)占69.53%、治疗组恢复期(T.R组)占53.97%;此外,Venn图结果表明,菌群失调导致模型组阴道菌群多样性降低,而阴道菌群移植后可将模型期中的102个OTUs上升至恢复期的172个OTUs,极大促进了阴道菌群多样性的恢复且增加了其微生物多样性。HE结果表明,阴道菌群移植可极大缓解大鼠子宫组织出现的炎症反应,降低内膜充血和炎性细胞浸润;从基因水平或蛋白水平显著降低了大鼠促炎因子IL-1β、TNF-α和IL-6的含量(p0.01)。综上所述,研究者首次提出阴道菌群移植治疗阴道细菌感染疾病的理念,发现阴道菌群移植可显著缓解阴道组织学病变,减缓其炎性因子释放,并有助于阴道微生态动态平衡的重建。本研究的开展,为阴道菌群移植疗法的深入研究提供了基础数据和应用依据。
[Abstract]:Bacterial Vaginosissis (BV) is a kind of gynecologic inflammation caused by the imbalance of vaginal microecological environment, often accompanied by pelvic inflammation, endometritis, infertility and other complications. As an important functional flora in the vagina, lactic acid bacteria play an important role in the process of maintaining the steady state of the vagina environment. The decrease in the number of lactic acid bacteria will lead to the increase of pH value and the weakening of the acidity of vagina, which will lead to Gardnebacterium vaginalis. A large number of pathogenic pathogens such as bacillus proliferate, resulting in different degrees of gynecological inflammation. At present, antibiotics are still the main treatment for gynecological diseases of vagina, but the abuse of antibiotics often leads to drug resistance of host to antibiotics and destruction of normal functional flora of vagina, resulting in further imbalance of microecological environment of vagina. Gynecological disease is easy to relapse and difficult to cure the situation. In view of the good effect of fecal bacteria transplantation in regulating intestinal flora, the concept of vaginal microflora transplantation was first put forward by the research team. The vaginal flora obtained from the vaginal secretions of healthy hosts was transplanted into the vagina of women with bacterial vagina infection, so as to reconstruct the microecological balance of the vaginal flora of the patients, promote the recovery of the vaginal environment and inhibit the proliferation of pathogenic bacteria. At the same time, the purpose of treating vaginal gynecological diseases is achieved. In this paper, the model of bacterial vagina infection in rats was studied to evaluate the therapeutic effect of vaginal microflora transplantation. The results showed that the total number of bacteria in vaginal secretions collected from healthy rats was about 105 CFU / mL, among which the content of lactic acid bacteria was about 104 CFU / mL, accounting for 7.8% of the total bacteria. The results of high-throughput sequencing showed that 622 OTUs were obtained, and 103 OTUs were found in each group of samples. The vaginal flora is mainly composed of (Aggregatibacter), Streptobacillus, Fusobacterium and Porphyromonas. Among them, 48.17% were dominant coagulans (group C), 59.37 were in model group (M group), 27.06g in model group (M.M group), 48.92% in model group (M.R group), 69.53 in treatment period (T.M group), and 69.53 in treatment group (T.R group), and 27.06% in model group (M.M group), 48.92% in model group (M.R group), 69.53% in treatment group (T.M group). 53.97; in addition, the Venn diagram shows that The diversity of vaginal flora in the model group was decreased due to the imbalance of the flora. However, after vaginal microflora transplantation, 102 OTUs in the model period were increased to 172 OTUs in the recovery period, which greatly promoted the recovery of vaginal flora diversity and increased the microbial diversity of vaginal flora. Vaginal microflora transplantation significantly alleviated the inflammatory reaction in rat uterus, reduced endometrial congestion and inflammatory cell infiltration, and significantly decreased the contents of IL-1 尾 -TNF- 伪 and IL-6 at gene level or protein level (p0.01). To sum up, the researchers first put forward the concept of vaginal microflora transplantation for the treatment of vaginal bacterial infection disease, and found that vaginal microflora transplantation can significantly alleviate the vagina histological lesions, slow down the release of inflammatory factors. It is helpful to reconstruct the dynamic balance of vagina microecology. The development of this study provides basic data and application basis for the further study of vaginal flora transplantation therapy.
【学位授予单位】：南昌大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R711.3

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