The effect of the penile microbiome on BV, GUD, and genital epithelial trauma

阴茎微生物群对 BV、GUD 和生殖器上皮创伤的影响

• 批准号: 9315716
• 负责人: Supriya Dinesh Mehta
• 金额: $ 46.97万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-08-01 至 2020-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9315716
• 关键词: Affect; Africa South of the Sahara; African; Anaerobic Bacteria; Anti-Retroviral Agents; Bacteria; Bacterial Vaginosis; Behavior; Behavior Therapy; Behavioral; Biological Factors; Cells; Clinical; Couples; Disease; Epithelial; Female; Fusobacteria; Genital system; Genitourinary system; Goals; HIV; HIV Infections; Health; Hemorrhage; Heterosexuals; Human Herpesvirus 2; Hygiene; Infection; Inflammation; Inflammatory; Interruption; Intervention; Intuition; Investigation; Kenya; Lead; Link; Low Prevalence; Male Circumcision; Maps; Measures; Medical; Menstruation; Modeling; Oral Ulcer; Oral mucous membrane structure; Outcome; Participant; Pathogenicity; Periodontal Diseases; Pharmacology; Population; Pregnancy Outcome; Property; Prospective cohort; Recovery; Regimen; Reporting; Risk; Risk Reduction; Sex Behavior; Sexual Partners; Skin; Testing; Time; Tissues; Topical Antibiotic; Trauma; Ulcer; Vagina; Variant; Woman; antimicrobial; cohort; contraceptive practice; cost effective; cytokine; effective intervention; experience; improved; men; microbicide; penile microbiome; prevent; protective effect; public health relevance; pyrosequencing; rRNA Genes; scale up; sex; stem; transmission process; vaginal microbiome; Affect; Africa South of the Sahara; African; Anaerobic Bacteria; Anti-Retroviral Agents; Bacteria; Bacterial Vaginosis; Behavior; Behavior Therapy; Behavioral; Biological Factors; Cells; Clinical; Couples; Disease; Epithelial; Female; Fusobacteria; Genital system; Genitourinary system; Goals; HIV; HIV Infections; Health; Hemorrhage; Heterosexuals; Human Herpesvirus 2; Hygiene; Infection; Inflammation; Inflammatory; Interruption; Intervention; Intuition; Investigation; Kenya; Lead; Link; Low Prevalence; Male Circumcision; Maps; Measures; Medical; Menstruation; Modeling; Oral Ulcer; Oral mucous membrane structure; Outcome; Participant; Pathogenicity; Periodontal Diseases; Pharmacology; Population; Pregnancy Outcome; Property; Prospective cohort; Recovery; Regimen; Reporting; Risk; Risk Reduction; Sex Behavior; Sexual Partners; Skin; Testing; Time; Tissues; Topical Antibiotic; Trauma; Ulcer; Vagina; Variant; Woman; antimicrobial; cohort; contraceptive practice; cost effective; cytokine; effective intervention; experience; improved; men; microbicide; penile microbiome; prevent; protective effect; public health relevance; pyrosequencing; rRNA Genes; scale up; sex; stem; transmission process; vaginal microbiome

DESCRIPTION (provided by applicant): Medical male circumcision (MMC) reduces the risk of heterosexual HIV acquisition in African men by 60%. In both our MMC trial in Kenya and the Ugandan MMC trial, circumcised men had lower prevalence and amount of penile anaerobic bacteria, several species of which are associated with Bacterial vaginosis (BV). The benefit is transferred to female sex partners of circumcised men, who had a 40-60% reduced risk of BV. MMC reduced genital ulcer disease (GUD) by 37-52%, and reduced GUD in female sex partners of circumcised men by 32%. Among men in our trial in Kenya, Fusobacteria and Sneathia had 6-fold greater odds of recovery from non-herpetic GUD compared to herpetic GUD. These two BV-related anaerobes are more common among uncircumcised men, and cause oral ulcers and periodontal disease. Their reduction may explain the reduction in non-herpetic GUD in circumcised men and their female sex partners. Cuts, abrasions, scratches, and bleeding of the vaginal or penile skin occur in 30-50% of men and women in our studies in Kenya, and are reduced by 40-60% among circumcised men and their female sex partners. Penile anaerobic bacteria are a common link between MMC and reductions in BV and GUD, and may also explain the reduced genital epithelial trauma among circumcised men and their sex partners. We propose to identify under what conditions the penile microbiome leads to BV, GUD, and genital epithelial trauma in men and their female sex partners. Within a prospective cohort of 204 heterosexual couples, we will measure the penile and vaginal microbiome four times over a one year period using pyrotag sequencing of the 16S rRNA gene. We will (Aim 1) determine how the penile microbiome leads to BV, GUD, and genital epithelial trauma, and factors that influence these associations. We will (Aim 2) define factors causing variation in the penile microbiome over time and across men. We will (Aim 3) map specific penile and vaginal bacteria to increased genital inflammatory cytokine levels, and elucidate the link between inflammatory cytokines and genital epithelial trauma. We need to determine how MMC reduces these co-factors for HIV infection to achieve benefits among uncircumcised men and to augment the protective effect of MMC. Pharmacologic interventions to improve penile microbiome health may include systemic or topical antimicrobials, or microbicides incorporating cytokine modulators. We need to identify specific bacteria to determine appropriate classes of antimicrobials, and whether the extent or type of inflammation induced can be modified. If specific behaviors - such as sex during a woman's menstruation or genital hygiene - are associated with types or amounts of harmful penile bacteria, then behavioral interventions will be tested. The potential benefits of interventions stemming from this investigation are: (1) reduced HIV acquisition and transmission through reduction of BV, GUD, and genital epithelial trauma as co-factors for infection, and (2) improved pregnancy outcomes and genitourinary health.

描述（由申请人提供）：医学男性包皮环切术（MMC）将非洲男性异性恋HIV获取的风险降低了60％。在我们在肯尼亚的MMC试验和乌干达MMC试验中，割礼的男性患病率较低，阴茎厌氧菌细菌的次数较低，其中几种与细菌性阴道病（BV）有关。利益转移给了割礼的男性的女性伴侣，后者降低了BV的风险40-60％。 MMC将生殖器溃疡疾病（GUD）降低了37-52％，并使割礼男性的女性性伴侣的GUD降低了32％。在我们在肯尼亚的试验中，与疱疹性GUD相比，在肯尼亚的审判中，从非疱疹性GUD中恢复的几率更大6倍。这两种与BV相关的厌氧菌在未割礼的男性中更为常见，并引起口腔溃疡和牙周疾病。他们的减少可以解释割礼的男人及其女性性伴侣的非疱疹性GUD的减少。在我们在肯尼亚的研究中，在30-50％的男性和女性中，阴道或阴茎皮肤的剪切，擦伤，划痕和出血，在割礼的男人及其女性性伴侣中减少了40-60％。阴茎厌氧菌是MMC与BV和GUD减少之间的常见联系，也可以解释割礼的男人及其性伴侣的生殖器上皮创伤减少。我们建议在男性及其女性性伴侣的BV，GUD和生殖器上皮创伤中确定阴茎微生物组会导致BV，GUD和生殖器上皮创伤。在204个异性恋夫妇的前瞻性队列中，我们将使用16S rRNA基因的Pyrotag测序在一年内四次测量阴茎和阴道微生物组。我们将（AIM 1）确定阴茎微生物组如何导致BV，GUD和生殖器上皮创伤以及影响这些关联的因素。我们将（AIM 2）定义导致阴茎微生物组变化的因素，随着时间的流逝和跨男性。我们将（AIM 3）绘制特定的阴茎和阴道细菌以增加生殖器炎症性细胞因子水平，并阐明炎性细胞因子与生殖器上皮创伤之间的联系。我们需要确定MMC如何降低这些共同因素以使HIV感染以在未割伤的男性中实现益处并增强MMC的保护作用。改善阴茎微生物组健康的药理干预措施可能包括全身性或局部抗菌剂，或掺入细胞因子调节剂的菌心。我们需要确定特定的细菌来确定适当的抗菌药物类别，以及是否可以修改炎症的程度或类型。如果特定的行为（例如女性月经期间的性行为或生殖器卫生）与有害阴茎细菌的类型或量有关，则将测试行为干预措施。这项研究引起的干预措施的潜在益处是：（1）通过减少BV，GUD和生殖器上皮创伤作为感染的共同因素，减少HIV的获取和传播，以及（2）改善妊娠结果和泌尿生殖健康。