Lubricant Use and the Vaginal Microbiome

润滑剂的使用和阴道微生物组

• 批准号: 9052986
• 负责人: REBECCA M. BROTMAN
• 金额: $ 79.42万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-02-05 至 2021-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9052986
• 关键词: Affect; Anti-Bacterial Agents; Anti-Inflammatory Agents; Anti-inflammatory; Attention; Bacteria; Bacterial Vaginosis; Behavioral; Biological Assay; Biological Markers; Cell Death; Cell secretion; Cells; Chlamydia; Chlorhexidine; Clinical; Clinical Trials; Controlled Study; Cosmetics; DNA; Data; Development; Dose; Dryness; Dyspareunia; Epidemiologic Studies; Epithelial; Epithelial Cells; Epithelium; Evaluation; Female; Fibronectins; Formulation; Funding; Glycerol; Glycogen; Gynecologic; HIV; Human; Human Microbiome; Immune response; Immunologic Markers; Incidence; Infection; Inflammatory; Isomerism; Lactate Dehydrogenase; Lactic acid; Lactobacillus; Lead; Lubricants; Measurement; Measures; Medical Device; Methods; Mucous body substance; Observational Study; Organism; Parabens; Participant; Play; Postmenopause; Predisposition; Procedures; Propylene Glycols; Protozoa; Quality of life; Radiology Specialty; Recording of previous events; Recruitment Activity; Reporting; Reproductive Tract Infections; Research; Ribosomal RNA; Risk; Role; Safety; Sampling; Sexually Transmitted Diseases; Skin; Surface; Surveys; Swab; Symptoms; Time; Toxic effect; Toxicant exposure; Transvaginal Ultrasound; Trauma; Ultrasonography; United States National Institutes of Health; Urinary tract; Urinary tract infection; Vagina; Vaginal Discharge; Viral; Woman; Work; clinical practice; cohort; cost; cytokine; design; diaries; digital; improved; interest; microbiome; microbiota; multidisciplinary; novel; pleasure; prevent; public health relevance; rRNA Genes; repository; reproductive tract; response; safety testing; self esteem; sex; social; time use; vaginal lactobacilli; vaginal microbiome

 DESCRIPTION (provided by applicant): Twenty-five percent of U.S. women report frequent use of vaginal lubricants to reduce discomfort and increase pleasure during sex. Clinically, lubricants are also used for digital exams and procedures such as trans-vaginal ultrasound (T-VUS). Among postmenopausal women, 50% use lubricants due to vaginal dryness and dyspareunia. The first line treatment for these women is non-hormonal vaginal lubricants. Recent studies have questioned the safety of current lubricants, yet there is little available data A healthy vagina is protected by Lactobacillus spp. that acidify the vagina with lactic acid, a potent bacteriocide and viricide. Disruption of this healthy microbiome markedly increases susceptibility to reproductive tract infections. We hypothesize that lubricants can disrupt the vaginal microbiome and increase risk to infections. Most vaginal lubricants contain hypertonic humectants such as glycerol or propylene glycol together with antibacterial preservatives, parabens and sometimes chlorhexidine. The active ingredients are "generally recognized as safe" (GRAS) by the FDA, hence are not subject to human clinical trials. However, at high concentrations or with frequent use, these ingredients may have toxic effects. It is unknown if hypertonic antibacterial lubricants affect the vaginal microbiota. We propose three aims to study the effect of lubricant on the vaginal microenvironment: 1) Evaluate the effects of lubricant on the temporal dynamics of vaginal microbiota with two methods: 1A) Perform a controlled observational study of one-time use of vaginal lubricant by recruiting women who are presenting for T-VUS, a procedure in which lubricant is applied to a T-VUS probe. This study will standardize the lubricant brand and dose by using the hypertonic lubricant currently in use by the Department of Radiology. Participants will self-collect daily samples prior to T-VUS for 1 week and twice-weekly for 9- weeks after TVUS. Changes in bacterial composition will be assessed using 16S rRNA gene analysis. 1B) Conduct a secondary analysis of existing data (behavioral diaries, clinical exams and 16S rRNA sequences) collected from a cohort of 130 women who were followed for 10 weeks in a prior study as part of the Human Microbiome Project (HMP). Participants self-collected mid-vaginal swabs daily and all samples are stored in a freezer repository. Lubricant use was reported by 37 women on 140 occasions. Samples collected every other day have already undergone DNA extraction and 16S rRNA sequencing (NIH RO1-GM103604). 2) Examine the effects of lubricant on the vaginal microenvironment in samples obtained from Aims 1A and 1B by assessing pH, D- and L-isomers of lactic acid and inflammatory cytokines. 3) Determine if lubricants have toxic effects on the vaginal epithelium using measurements of cell shedding rates, glycogen (necessary for lactobacilli survival), fibronectin (a marker of epithelial disruption), and lactate dehydrogenase (a marker of cell death) in samples collected in Aim 1A. This study will contribute to the development of safer formulations for personal and clinical lubricants.

 描述（由申请人提供）：25%的美国女性报告经常使用阴道润滑剂来减少性生活中的不适和增加快感。在临床上，润滑剂还用于数字检查和经阴道超声（T-VUS）等程序。在绝经后妇女中，50%的人由于阴道干燥和性交困难而使用润滑剂。这些女性的一线治疗是非激素阴道润滑剂。最近的研究对目前润滑剂的安全性提出了质疑，但几乎没有可用的数据。用乳酸酸化阴道，一种有效的杀菌剂和杀病毒剂。这种健康微生物组的破坏显着增加了对生殖道感染的易感性。我们假设润滑剂可以破坏阴道微生物组并增加感染风险。大多数阴道润滑剂含有高渗湿润剂，如甘油或丙二醇，以及抗菌防腐剂，对羟基苯甲酸酯，有时氯己定。这些活性成分被FDA“公认为安全”（GRAS），因此不受人体临床试验的影响。然而，在高浓度或频繁使用时，这些成分可能具有毒性作用。尚不清楚高渗抗菌润滑剂是否会影响阴道微生物群。我们提出了三个目的来研究润滑剂对阴道微环境的影响：1）用两种方法评估润滑剂对阴道微生物群的时间动态的影响：1A）通过招募正在进行T-VUS的女性来进行一次性使用阴道润滑剂的对照观察研究，T-VUS是一种将润滑剂应用于T-VUS探头的程序。本研究将通过使用放射科目前使用的高渗润滑剂来标准化润滑剂品牌和剂量。受试者将在T-VUS前每天自我采集样本，持续1周，在TVUS后每周两次，持续9周。将使用16 S rRNA基因分析评估细菌组成的变化。 1B）对从130名女性队列中收集的现有数据（行为日记，临床检查和16 S rRNA序列）进行二次分析，这些女性在之前的研究中被跟踪了10周，作为人类微生物组计划（HMP）的一部分。参与者每天自我采集阴道中段拭子，所有样本均储存在冷冻库中。37名妇女报告了140次使用润滑剂的情况。每隔一天采集的样本已经进行了DNA提取和16 S rRNA测序（NIH RO 1-GM 103604）。 2)通过评估pH值、乳酸的D-和L-异构体以及炎性细胞因子，检查润滑剂对从目标1A和1B获得的样本中阴道微环境的影响。 3)通过测量目标1A中采集的样本中的细胞脱落率、糖原（乳酸杆菌存活所必需的）、纤连蛋白（上皮破坏的标志物）和乳酸脱氢酶（细胞死亡的标志物），确定润滑剂是否对阴道上皮具有毒性作用。 这项研究将有助于开发更安全的个人和临床润滑剂配方。