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Background  Medical male circumcision (MMC) reduces the risk of genital ulcer disease (GUD) in men by 50%. In Ugandan and Kenyan trials, a sexually transmissible agent was not identified in 50–60% of GUD specimens by polymerase chain reaction (PCR) assay. We sought to better define the etiology of GUD in men participating in the Kenyan trial and examine how MMC affects GUD etiology.    Methods  We defined GUD of unknown etiology as negative for HSV (type 1 and type 2),  T. pallidum , and  H. ducreyi  by PCR, and negative for HSV-2 and  T. pallidum  by serology. We identified bacterial microbiota in a subset of 59 GUD specimens using multitag pyrosequencing of the 16S rRNA gene, and compared results by unknown vs. STI-associated etiology. Statistical analysis employed Bray-Curtis similarity measure of bacterial community by etiology, hierarchical clustering and logistic regression.    Results  In 59 GUD specimens from 59 men, 23 (39%) had unknown etiology. Bacterial diversity was greater in GUD of unknown than STI etiology (p = 0.01). Fusobacteria ( Fusobacterium  spp. and  Sneathia  spp.) were more commonly detected in men with GUD of unknown etiology [adjusted OR = 5.67; 95% CI: 1.63–19.8] as were  Oxobacter  spp. and  Anaerovorax  spp. [adjusted OR = 3.12; 95% CI: 0.83–11.7]. Sequences from these four anaerobic bacterial taxa were more often detected in uncircumcised men than circumcised men (p<0.05).    Conclusions  Anaerobic bacteria are more common in genital ulcers of uncircumcised men. The specific anaerobic bacteria associated with GUD of unknown etiology have cytotoxic properties that can exacerbate epithelial disruptions leading to ulcer-like appearance. MMC may reduce GUD through a reduction in these anaerobic bacteria.

Microbial Diversity of Genital Ulcer Disease in Men Enrolled in a Randomized Trial of Male Circumcision in Kisumu, Kenya