"Transmission of the human immunodeficiency virus (HIV) primarily occurs across mucosal surfaces. In particular, the rectum and colon mucosa are important as a portal of entry and during early disease progression, respectively. In the United States, 66% of all new HIV infections in 2017 were in men who have sex with men (MSM), with receptive anal intercourse being the main mode of transmission. Substantial gut microbiome compositional shifts have been previously described in HIV-infected populations; however, we now know the most prominent compositional changes are associated with sexual behavior. The MSM gut microbiome is dominated by Prevotella species compared with the Bacteroides-rich microbiome of culturally westernized men who have sex with women (MSW). Microbiome shifts associated with HIV infection are more subtle, typically require a large cohort to observe, and have been linked with low current and nadir CD4+ T cell counts and viremia. Our group investigated HIV-associated microbiome compositional effects on immune activation in vitro 9 and recently published an evaluation of the effects of human fecal microbiota transplant on immune activation in a gnotobiotic mouse model. These studies revealed the fecal microbiota of MSM, regardless of HIV status, elevates immune activation over that seen with the fecal microbiota of MSW. Additionally, we observed that the MSM microbiota enhanced in vitro HIV infection. Here, the discussion will focus on the question, can the microbiota of MSM influence HIV transmission? We provide additional data that suggests the unique gut microbiota in MSM drives the influx of a population of CD4+ T cells expressing the HIV co-receptor CCR5 into the gut, supporting a link between the gut microbiota in HIV-negative MSM, the mucosal immune environment, and HIV transmission."