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)，包括奈瑟氏菌 淋病(NG)和沙眼衣原体(CT)是非常令人关注的。直肠NG/CT与2 使感染艾滋病毒的风险增加8倍，并可能加剧男男性接触者中艾滋病毒的持续高水平传播 人口。其次，虽然大多数直肠性传播感染没有症状，但它们可能会导致发病率和长期的 精选患者的后遗症。最后，直肠感染可能是发育的一个重要的蓄水池。 抗药性。新出现的NG抗菌素耐药性集中在MSM，并有可能 损害了NG治疗在这一人群中的疗效。面对艾滋病毒/性传播感染比率的上升和不断上升 耐药、新的非抗生素方法防治MSM直肠性传播感染迫在眉睫。 在女性中，定植于阴道的细菌(“阴道微生物区系”(VMB))的破坏 肯定与获得泌尿生殖系统NG/CT有关，而“最佳”VMB提供显著的保护，使其免受 这些性传播疾病。直肠微生物区系可能比VMB更容易修改，如果被证明与 对于直肠性传播感染的风险或保护，可能是预防直肠性传播感染的一个新的治疗靶点。 然而，数据是稀疏的。一项欧洲单项横断面研究比较了MSM患者的直肠微生物区系 有和没有直肠NG/CT，但不能区分差异是与易感性有关还是 直肠STI的后果。此外，我们对男男性接触者直肠微生物区系知之甚少，来自于 美国和欧洲，但世界其他地区的男男性接触者，包括撒哈拉以南非洲，占 相当大比例的新性传播感染病例，可能会受到新出现的NG药物的不成比例的影响 耐药性，由于筛查和治疗策略不充分。迄今为止，是什么决定了直肠 MSM的微生物区系，特别是在非西方人群中，无论是直肠NG/CT，都知之甚少 感染对直肠微生物区系的影响正在研究中，以及直肠微生物区系是否具有特定的特征 与直肠STI获得性感染相关的风险或保护尚不清楚。 因此，我们建议利用来自TRUST/RV368研究的现有纵向直肠样本，a 2737名尼日利亚MSM队列每3个月随访一次，持续18个月，进行直肠NG/CT测试、检查 和行为问卷。我们将在直肠STI前和直肠STI时评估直肠微生物区系。 300例病例(150例CT，150例NG)与200例未获得直肠的对照样本的诊断 随访期的性传播感染。我们将评估行为因素对直肠微生物区系的影响，并比较 直肠NG或CT感染前及感染时的直肠微生物区系。最后，我们将识别直肠 与直肠NG和CT感染风险相关的微生物区系特征，控制 容易接受的肛交等混杂因素。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。