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 ...