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 跨性别者是指那些性别认同与其出生时指定的性别不相符的人 性别。 2016 年，美国约有 140 万成年人被认定为跨性别者。跨性别者可能会选择 通过性别确认激素或手术进行医学上的转变。跨性别者感染艾滋病毒的风险更高 其他性传播感染（STI），但人们对性别肯定医疗护理对性传播感染（STI）的影响知之甚少。 生殖器微环境，包括导致艾滋病毒和性传播感染的微生物组和局部免疫学 顺性别个体的风险。因此，美国国立卫生研究院（NIH）确定了对创新研究的主要需求，该研究的特点是 用于性别重置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 （出生时被指定为男性，但性别认同为女性）接受过阴道成形术（手术创建一个 新阴道病，通常使用阴茎和阴囊皮肤），而这些女性经常出现新阴道病 生态失调，但对其潜在的病理生理学知之甚少。顺位阴茎和阴道微环境 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，但我们对其组成和作用的理解 定植于新阴道的微生物群很少，并且完全缺乏免疫结果。在跨性别男人中， 阴道切除术很少见（<2%），但估计 69% 的患者使用性别确认睾酮疗法。男性化 激素治疗对阴道上皮有显着影响，导致细胞增殖减少和 糖原的产生。这类似于顺式女性更年期期间观察到的阴道萎缩，这会影响 阴道微生物群，并对性健康和生活质量产生负面影响。可用信息很少 阴道微生物群与炎症以及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群，定义了与局部相关的微生物 炎症，然后测试生殖器微环境与药物、生殖器 暴露和激素治疗，以指导新型干预措施的开发以及临床和行为 目前缺乏最佳实践。我们将通过彻底、严格的执行来实现这些目标 对跨性别男性和女性的阴道和新阴道微生物群进行纵向描述（目标 1），然后 定义这些微生物组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 以及顺式个体的性传播感染风险（目标 2）。我们的研究 TransBiota 将利用 IRB 批准的试点和验证 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： 纠正与微生物组分析相关的实验错误。了解生殖器 微环境及其在跨性别女性和男性性健康中的作用是实现这一目标的重要先决条件 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 开发新的干预措施以实现最佳的生殖器健康和保护。