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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

基本信息

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
项目类别：
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

项目摘要

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.

在与男性发生性行为的男性（MSM）中，直肠性传播感染（sti）包括奈瑟菌