Franz Kristina, Markó Lajos, Mähler Anja, Chakaroun Rima, Heinitz Sascha, Schlögl Haiko, Sacher Julia, Steckhan Nico, Dechend Ralf, Adams Noah, Andersen Marianne, Glintborg Dorte, Viehweger Martin, Bahr Lina Samira, Forslund-Startceva Sofia Kirke
Experimental and Clinical Research Center, Charité - Universitätsmedizin Berlin and Max Delbrück Center for Molecular Medicine, Berlin, Germany
Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany.
BMJ Open. 2025 Jan 9;15(1):e087982. doi: 10.1136/bmjopen-2024-087982.
Cardiovascular diseases (CVDs) present differently in women and men, influenced by host-microbiome interactions. The roles of sex hormones in CVD outcomes and gut microbiome in modifying these effects are poorly understood. The XCVD study examines gut microbiome mediation of sex hormone effects on CVD risk markers by observing transgender participants undergoing gender-affirming hormone therapy (GAHT), with findings expected to extrapolate to cisgender populations.
This observational, longitudinal cohort study includes baseline, 1- and 2-year follow-ups with transgender participants beginning GAHT. It involves comprehensive phenotyping and microbiome genotyping, integrating computational analyses of high-dimensional data. Microbial diversity will be assessed using gut, skin, and oral samples via 16S rRNA and shotgun metagenomic sequencing of gut samples. Blood measurements will include sex hormones, CVD risk markers, cardiometabolic parameters, cytokines, and immune cell counts. Hair samples will be analysed for cortisol. Participants will complete online questionnaires on physical activity, mental health, stress, quality of life, fatigue, sleep, pain, and gender dysphoria, tracking medication use and diet to control for confounders. Statistical analyses will integrate phenomic, lifestyle, and multi-omic data to model health effects, testing gut microbiome mediation of CVD risk as the endocrine environment shifts between that typical for cisgender men to women and vice versa.
The study adheres to Good Clinical Practice and the Declaration of Helsinki. The protocol was approved by the Charité Ethical Committee (EA1/339/21). Signed informed consent will be obtained. Results will be published in peer-reviewed journals and conferences and shared as accessible summaries for participants, community groups, and the public, with participants able to view their data securely after public and patient involvement review for accessibility.
The XCVD study was registered on ClinicalTrials.gov (NCT05334888) as 'Sex-differential host-microbiome CVD risk - a longitudinal cohort approach (XCVD)" on 4 April 2022. Data set link can be found at https://classic.
gov/ct2/show/NCT05334888.
心血管疾病（CVDs）在男性和女性中的表现有所不同，受到宿主 - 微生物群相互作用的影响。性激素在心血管疾病结局中的作用以及肠道微生物群在调节这些作用方面的作用尚不清楚。XCVD研究通过观察接受性别确认激素治疗（GAHT）的跨性别参与者，研究肠道微生物群对性激素对心血管疾病风险标志物影响的介导作用，研究结果有望推广到顺性别群体。
这项观察性纵向队列研究包括对开始接受GAHT的跨性别参与者进行基线、1年和2年随访。它涉及全面的表型分析和微生物群基因分型，整合高维数据的计算分析。将通过16S rRNA以及肠道样本的鸟枪法宏基因组测序，使用肠道、皮肤和口腔样本评估微生物多样性。血液检测将包括性激素、心血管疾病风险标志物、心脏代谢参数、细胞因子和免疫细胞计数。将分析头发样本中的皮质醇。参与者将完成关于身体活动、心理健康、压力、生活质量、疲劳、睡眠、疼痛和性别焦虑的在线问卷，跟踪药物使用和饮食以控制混杂因素。统计分析将整合表型组、生活方式和多组学数据以对健康影响进行建模，测试随着内分泌环境在顺性别男性与女性的典型环境之间转换时，肠道微生物群对心血管疾病风险的介导作用。
该研究遵循良好临床实践和《赫尔辛基宣言》。该方案已获得夏里特伦理委员会（EA1/339/21）批准。将获得签署的知情同意书。研究结果将发表在同行评审期刊和会议上，并作为通俗易懂的摘要分享给参与者、社区团体和公众，参与者在经过公众和患者参与的可及性审查后能够安全地查看自己的数据。
XCVD研究于2022年4月4日在ClinicalTrials.gov上注册为“性别差异宿主 - 微生物群心血管疾病风险 - 纵向队列研究方法（XCVD）”（NCT05334888）。数据集链接可在https://classic.clinicaltrials.gov/ct2/show/NCT05334888找到。
