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

TransBiota：跨性别男性和女性的生殖器微生物群、炎症和艾滋病毒风险

• 批准号: 10612898
• 负责人: Jessica Lynn Prodger
• 金额: $ 17.53万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-22 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10612898
• 关键词: 16S ribosomal RNA sequencing; Address; Adult; Affect; Anaerobic Bacteria; Anatomy; Atrophic; Bacteria; Behavior; Behavioral; Biological; Birth; Caring; Cell Proliferation; Cells; Characteristics; Clinical; Corynebacterium; Development; Enrollment; Epithelium; Exposure to; Female; Functional disorder; Future; Gender Identity; Genital; Genitalia; Glycogen; Goals; HIV; HIV risk; Health; Home; Hygiene; Hysterectomy; Immune; Immunologics; Immunology; Individual; Inflammation; Institutional Review Boards; Intervention; Knowledge; Lactobacillus; Logistic Regressions; Medical; Medicine; Menopause; Microbe; Modeling; Mucous Membrane; Operative Surgical Procedures; Outcome; Ovariectomy; Oxygen; Participant; Pathology; Peptostreptococcus; Persons; Physiological; Physiology; Population; Postmenopause; Predisposition; Prevotella; Production; Quality of life; Questionnaires; Research; Risk; Role; Sampling; Sex Behavior; Sexual Health; Sexual Reassignment; Sexually Transmitted Diseases; Site; Skin; Sociology; Structure; Swab; Testing; Testosterone; Time; United States; United States National Institutes of Health; Vagina; Woman; assigned male at birth; cis-female; cis-male; cisgender; clinical care; clinical development; cohort; dysbiosis; female sex hormone; gender affirmation; gender affirming hormones; gender affirming medical care; gender nonconforming; genital microbiome; genital surgery; high risk; hormone therapy; immunological status; improved; infection risk; inflammatory marker; innovation; microbiome; microbiome analysis; microbiota; neovagina; novel; novel strategies; penis; psychologic; recruit; research and development; sex; sex assigned at birth; transgender; transgender men; transgender women; vaginal microbiome; vaginal microbiota; vaginectomy; vaginoplasty

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.

概括 跨性别者（跨性别）个人是那些具有不符合其出生分配的性别认同的人 性别。 2016年，美国约有140万成年人被确定为变性人。跨性别者可以选择 通过性别表达的激素或手术进行医学过渡。跨性别者患艾滋病毒的风险更高 其他性传播感染（STI），但知之甚少 生殖器微环境，包括微生物组和局部免疫学，有助于HIV和STI 赋予人物的风险。因此，NIH确定了对创新研究的主要需求 用于性别重新分配的干预措施的生物学和免疫学影响。大约1/4的跨性别女性 （出生时分配的男性，但具有女性认同）经历了阴道胶状（手术创造 Neovagina，通常使用阴茎和阴囊皮），而这些妇女经常出现Neovagina 营养不良，对潜在的病理生理学知之甚少。顺式的阴茎和阴道微环境 男人和女人是艾滋病毒和性传播感染风险的关键决定者，但我们对作用和角色的理解 菌群定居于新生诺瓦基纳，完全缺乏免疫结果。在跨性别者中 阴道切除术很少见（<2％），但估计有69％使用性别肯定的睾丸激素治疗。男性化 马酮治疗对阴道上皮有重大影响，导致细胞增殖降低和 糖原产生。这类似于在CIS女性更年期期间观察到的阴道萎缩，这会影响 阴道菌群，对性健康和生活质量产生负面影响。几乎没有信息 关于阴道菌群与注射以及阴道萎缩的发展和 跨性别男人的艾滋病毒和性传播感染风险。鉴于这些未知数，这项研究的短期目标是描述 跨性别女性和男性的新血管和阴道微生物组定义与局部相关的微生物 炎症，然后测试生殖器微环境与药物之间的关联 暴露和马酮治疗，以指导新干预的发展以及临床和行为 目前缺乏的最佳实践。我们将通过执行彻底而严格的 跨性别男性和女性中阴道和新阴道微生物组的纵向描述（AIM 1），然后 定义这些微生物组与生殖器免疫学之间的关系，这是HIV的决定因素 和STI风险在顺式个人中（AIM 2）。我们的研究TransBiota将利用试验和验证的IRB批准 创新的基于家庭的抽样策略和创新的统计策略，该策略使科学严谨 纠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性和男性中性健康中的作用是实现的重要先决条件 我们改善跨性别男女生殖器护理的长期目标，并最终利用这些信息 为了制定新的干预措施，以实现最佳的生殖器健康和保护。