The rectal microbiome and incident rectal sexually transmitted infections

直肠微生物组和直肠性传播感染事件

• 批准号: 10349502
• 负责人: Susan Anne Tuddenham
• 金额: $ 20.07万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-02-11 至 2024-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10349502
• 关键词: 16S ribosomal RNA sequencing; Affect; Africa South of the Sahara; Anal Sex; Antibiotics; Antimicrobial Resistance; Bacteria; Behavioral; Chlamydia trachomatis; Cross-Sectional Studies; Data; Development; Diagnosis; Drug resistance; Drug-resistant Neisseria Gonorrhoeae; Escherichia; Europe; European; Foundations; Future; Genitourinary system; HIV; HIV Infections; Infection; Intervention; Lead; Link; Lubricants; Methods; Morbidity - disease rate; Neisseria gonorrhoeae; Nigerian; Patients; Peptostreptococcus; Play; Population; Predisposition; Prevotella; Questionnaires; Reporting; Risk; Role; STI prevention; Sampling; Sexually Transmitted Diseases; Shotgun Sequencing; Shotguns; Testing; Time; Treatment Efficacy; United States; Vagina; Visit; Woman; base; cohort; condoms; drug development; follow-up; improved; infection rate; long-term sequelae; male health; men who have sex with men; metagenome; microbial community; microbiota; microbiota profiles; new therapeutic target; novel; prevent; rectal; rectal microbiome; rectal microbiota; screening; sexual HIV transmission; transmission process; treatment strategy; vaginal microbiota

In men who have sex with men (MSM) rectal sexually transmitted infections (STIs) including Neisseria gonorrhoea (NG) and Chlamydia trachomatis (CT) are of great concern. Rectal NG/CT are associated with a 2 to >8 fold increased risk of HIV acquisition, and may fuel continued high level HIV transmission in the MSM population. Secondly, while most rectal STIs are asymptomatic, they may cause morbidity and long term sequelae in select patients. Finally, rectal infections may represent an important reservoir for the development of drug resistance. Emerging NG antimicrobial resistance is concentrated in MSM, and threatens to compromise the efficacy of NG treatment in this population. In the face of elevated HIV/STI rates and rising drug resistance, new non-antibiotic methods to prevent and treat rectal STIs in MSM are urgently needed. In women, disruptions in the bacteria colonizing the vagina (“vaginal microbiota” (VMB)) have been definitively linked to acquisition of urogenital NG/CT, while an “optimal” VMB offers significant protection from these STIs. The rectal microbiota may be more readily modifiable than the VMB, and if shown to correlate with risk or protection from rectal STIs, may plausibly represent a novel therapeutic target for rectal STI prevention. However, data are sparse. A single cross-sectional European study compared the rectal microbiota in MSM with and without rectal NG/CT, but could not distinguish whether differences related to susceptibility or were a consequence of rectal STI. Moreover, the little we know about the rectal microbiota of MSM comes from the United States and Europe but MSM in other parts of the world, including sub-Saharan Africa, account for a substantial proportion of new STI cases, and may be disproportionately affected by emerging NG drug resistance, due to inadequate screening and treatment strategies. To date, what determines the rectal microbiota in MSM, particularly in non-Western populations, is poorly understood, whether rectal NG/CT infection changes the rectal microbiota is under studied, and whether specific rectal microbiota features associate with risk or protection from rectal STI acquisition is unknown. Therefore, we propose to leverage existing longitudinal rectal samples from the TRUST/RV368 study, a cohort of 2737 Nigerian MSM followed every 3 months for up to 18 months with rectal NG/CT testing, exams and behavioral questionnaires. We will assess the rectal microbiota at the visit prior to and at time of rectal STI diagnosis in 300 incident cases (150 CT, 150 NG) against samples from 200 controls who acquired no rectal STIs during follow-up. We will assess the impact of behavioral factors on the rectal microbiota, and compare the rectal microbiota before and at the time of rectal NG or CT infection. Finally, we will identify rectal microbiota signatures that associate with risk for incident rectal NG and CT infection, controlling for confounders such as receptive anal intercourse. In the long term this project will provide foundational data to inform future, larger studies, and may lead to novel interventions to treat and prevent rectal STIs in MSM.

男男性行为者 (MSM) 直肠性传播感染 (STI)，包括奈瑟菌 淋病（NG）和沙眼衣原体（CT）备受关注。直肠 NG/CT 与 2 HIV 感染风险增加 8 倍以上，并可能助长 MSM 中 HIV 持续高水平传播 人口。其次，虽然大多数直肠性传播感染是无症状的，但它们可能会导致发病和长期 特定患者的后遗症。最后，直肠感染可能是疾病发展的重要宿主。 的耐药性。新出现的 NG 抗菌药物耐药性集中在 MSM 中，并威胁到 影响 NG 治疗在该人群中的疗效。面对艾滋病毒/性传播感染发病率上升和 由于耐药性，迫切需要新的非抗生素方法来预防和治疗 MSM 直肠性传播感染。 在女性中，阴道定植细菌（“阴道微生物群”（VMB））受到破坏 与泌尿生殖 NG/CT 的获得明确相关，而“最佳”VMB 提供了显着的保护 这些性传播感染。直肠微生物群可能比 VMB 更容易改变，如果显示与 直肠性传播感染的风险或保护，可能代表直肠性传播感染预防的新治疗目标。 然而，数据很少。一项欧洲横断面研究比较了 MSM 的直肠微生物群 有或没有直肠 NG/CT，但无法区分差异是否与敏感性相关或是否与 直肠性传播感染的后果。此外，我们对 MSM 的直肠微生物群知之甚少来自 美国和欧洲，但世界其他地区（包括撒哈拉以南非洲地区）的 MSM 占 占新发性传播感染病例的很大一部分，并且可能受到新兴 NG 药物的不成比例的影响 由于筛查和治疗策略不足而产生耐药性。迄今为止，什么决定了直肠 MSM 中的微生物群，特别是非西方人群中的微生物群，人们知之甚少，无论是直肠 NG/CT 感染改变直肠微生物群的情况正在研究中，以及特定的直肠微生物群是否具有特征 与直肠性传播感染的风险或保护的相关性尚不清楚。 因此，我们建议利用 TRUST/RV368 研究中现有的纵向直肠样本， 2737 名尼日利亚 MSM 队列每 3 个月接受一次直肠 NG/CT 测试、检查，为期长达 18 个月 和行为问卷。我们将在直肠性传播感染之前和发生时就诊时评估直肠微生物群 对 300 个事件病例（150 个 CT，150 个 NG）进行诊断，对照来自 200 个未获得直肠疾病的对照样本 随访期间的性传播感染。我们将评估行为因素对直肠微生物群的影响，并比较 直肠 NG 或 CT 感染之前和时的直肠微生物群。最后我们来识别直肠 与直肠 NG 和 CT 感染风险相关的微生物群特征，控制 混杂因素，例如接受性肛交。从长远来看，该项目将为 为未来更大规模的研究提供信息，并可能导致治疗和预防 MSM 直肠性传播感染的新干预措施。