TransBiota: Genital microbiome, inflammation and HIV risk in trans men and women

总结 跨性别者（Transgender）是指那些性别认同与其出生时的性别不匹配的人。 性2016年，美国约有140万成年人被认定为变性人。跨性别者可以选择 通过性别确认激素或手术进行医学过渡。跨性别者感染艾滋病毒的风险更高， 其他性传播感染（STI），但很少有人知道性别肯定的医疗保健对 生殖器微环境，包括微生物组和局部免疫，这有助于艾滋病毒和性传播感染 cisgender的风险。因此，NIH确定了创新研究的主要需求， 用于性别重置的干预措施的生物和免疫影响。大约四分之一的跨性别女性 （出生时被指定为男性，但具有女性性别身份）接受了阴道成形术（手术创造一个 新阴道，通常使用阴茎和阴囊皮肤），虽然这些妇女经常出现新阴道， 生态失调，对潜在的病理生理学知之甚少。顺性生殖道感染患者阴茎和阴道微环境的研究 男性和女性是艾滋病毒和性传播感染风险的关键决定因素，但我们对构成和作用的理解 在新生阴道中定植的微生物群是罕见的，并且完全缺乏免疫结果。在变性人中， 阴道切除术是罕见的（<2%），但估计69%的使用性别肯定睾酮治疗。雄性化 激素治疗对阴道上皮具有显著的作用，导致细胞增殖减少， 糖原生成这类似于在绝经期观察到的阴道萎缩， 阴道微生物群，并对性健康和生活质量产生负面影响。的信息很少 阴道微生物群与炎症和阴道萎缩发展之间的关系， 跨性别男性的艾滋病毒和性传播感染风险。鉴于这些未知因素，本研究的短期目标是描述 跨性别女性和男性的新阴道和阴道微生物组，定义与局部 炎症，然后测试生殖器微环境和药物，生殖器 暴露和激素治疗，以指导新的干预措施的发展，以及临床和行为 最佳实践，这是目前所缺乏的。我们将通过执行一项全面而严格的 跨性别男性和女性阴道和新阴道微生物组的纵向描述（目标1），然后 确定这些微生物群与生殖器免疫学之间的关系，生殖器免疫学是艾滋病毒的决定因素 和性传播感染风险（目标2）。我们的研究，TransBiota，将利用一个试点和验证的IRB批准， 创新的家庭抽样策略和创新的统计策略，通过以下方式提供科学严谨性： 校正与微生物组分析相关的实验误差。了解生殖器 微环境及其在跨性别男女性健康中的作用是实现 我们的长期目标是改善跨性别女性和男性的生殖器护理，并最终利用这些信息 制定新的干预措施，以实现最佳的生殖器健康和保护。

SUMMARY Transgender (trans) individuals are those who have a gender identity that does not match their birth-assigned sex. About 1.4 million adults in the United States identified as transgender in 2016. Trans people may choose to medically transition through gender-affirming hormones or surgeries. Trans people are at higher risk for HIV and other sexually transmitted infections (STI), but little is known of the effect of gender-affirming medical care on the genital microenvironment, including the microbiome and local immunology, which contribute to HIV and STI risk in cisgender individuals. The NIH has thus identified a major need for innovative research characterizing the biological and immunological impact of interventions used for gender reassignment. About ¼ of trans women (assigned male at birth but with a female gender identity) have undergone vaginoplasty (surgical creation of a neovagina, typically using penile and scrotal skin), and while these women frequently present with neovaginal dysbiosis, little is known about the underlying pathophysiology. The penile and vaginal microenvironment in cis men and women is a critical determinant of HIV and STI risk, yet our understanding of the composition and role of microbiota colonizing the neovagina is scarce and completely lacking for immune outcomes. In trans men, vaginectomy is rare (<2%) but an estimated 69% use gender-affirming testosterone therapy. Masculinizing hormone therapy has significant effects on the vaginal epithelium that result in reduced cellular proliferation and glycogen production. This is similar to vaginal atrophy observed during menopause in cis women, which affects the vaginal microbiota and has negative impacts on sexual health and quality of life. Little information is available on the relationship between vaginal microbiota and inflammation and the development of vaginal atrophy and HIV and STI risk in trans men. Given these unknowns, the short-term goals of this research are to describe the neovaginal and vaginal microbiomes in trans women and men, define microbes associated with local inflammation, and then test for associations between the genital microenvironment and medicines, genital exposures, and hormone therapy, to guide the development of novel interventions, and clinical and behavioral best-practices, which currently are lacking. We will achieve these goals by performing a thorough and rigorous longitudinal description of the vaginal and neovaginal microbiomes in trans men and women (Aim 1) and then defining the relationship between these microbiomes and the genital immunology, a determining factor of HIV and STI risk in cis individuals (Aim 2). Our study, TransBiota, will leverage a piloted and validated IRB-approved innovative home-based sampling strategy and an innovative statistical strategy that affords scientific rigor by correcting for experimental errors associated with microbiome analyses. Understanding the genital microenvironment and its role in sexual health in trans women and men is an important prerequisite to achieve our long-term goals to improve genital care for trans women and men and to ultimately leverage this information for the development of novel interventions to achieve optimal genital health and protection.