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）的直肠性传播感染（STI），包括奈瑟菌 淋病（NG）和沙眼衣原体（CT）引起极大关注。直肠NG/CT与2 艾滋病毒感染的风险增加8倍以上，并可能助长MSM中持续的高水平艾滋病毒传播 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 选择患者的后遗症。最后，直肠感染可能是一个重要的水库的发展， 抗药性的证据。新出现的NG抗生素耐药性集中在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/性传播感染率上升和 因此，迫切需要新的非抗生素方法来预防和治疗MSM中的直肠性传播感染。 在女性中，阴道细菌（“阴道微生物群”（VMB））的破坏已经被证明是有效的。 与泌尿生殖道NG/CT的获得明确相关，而“最佳”VMB提供了显著的保护， 这些性传播感染直肠微生物群可能比VMB更容易改变，并且如果显示与VMB相关， 风险或保护免受直肠STI，可能是直肠STI预防的新治疗靶点。 然而，数据稀少。一项单一的横断面欧洲研究比较了MSM的直肠微生物群 有和没有直肠NG/CT，但不能区分差异是否与易感性有关， 直肠STI的后果。此外，我们对MSM直肠微生物群的了解很少， 美国和欧洲，但在世界其他地区，包括撒哈拉以南非洲， 很大比例的新的性传播感染病例，并可能不成比例地受到新兴NG药物的影响 由于筛查和治疗策略不足，导致耐药性。到目前为止，是什么决定了直肠 MSM中的微生物群，特别是在非西方人群中，了解甚少，无论是直肠NG/CT 感染改变直肠微生物群正在研究中，以及特定的直肠微生物群特征是否 与直肠STI获得的风险或保护有关的信息尚不清楚。 因此，我们建议利用来自TRUST/RV 368研究的现有纵向直肠样本， 2737名尼日利亚MSM队列每3个月随访一次，长达18个月，进行直肠NG/CT检测，检查 和行为问卷调查。我们将在直肠STI之前和发生时的访视中评估直肠微生物群 300例偶发病例（150例CT，150例NG）与200例对照组样本的诊断结果， 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 在直肠NG或CT感染之前和之时的直肠微生物群。最后，我们将确定直肠 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，如接受性肛交。从长远来看，该项目将提供基础数据， 为未来更大规模的研究提供信息，并可能导致新的干预措施来治疗和预防MSM中的直肠性传播感染。