Anaerobe‐Driven Inflammation and Epithelial Barrier Disruption in Genital HIV Acquisition

BACKGROUND: Genital microbiome dysbiosis is an important risk factor for the sexual acquisition of human immunodeficiency virus (HIV) in both the male and female genital tracts. The vaginal, penile and urethral mucosae are distinct microenvironments with characteristic microbiome compositions. However, all three sites can be colonised by a group of strictly anaerobic bacteria that are strongly associated with mucosal inflammation and HIV risk. Our understanding of the relationship between genital anaerobes and HIV acquisition has largely focused on mucosal target cell density and activation. Yet, genital anaerobes disrupt epithelial barrier integrity, a crucial component of mucosal defence. OBJECTIVE: To comprehensively evaluate the influence of genital anaerobes on epithelial barrier integrity in the context of HIV acquisition, across the penile, vaginal, and urethral mucosae. RESULTS: Within the vaginal microbiome, anaerobes have been studied extensively in the context of bacterial vaginosis and several mechanisms of mucosal barrier disruption, including mucus degradation, epithelial cell damage and junction protein cleavage, have been identified and linked to HIV risk. The effects of these same bacteria are less defined in the context of the penile and urethral epithelia, despite their prevalence and association with HIV acquisition. CONCLUSIONS: Further investigation of genital anaerobe-mediated barrier disruption in both sexes is needed to elucidate shared and site-specific mechanisms influencing HIV transmission. This knowledge is essential to understanding HIV risk and developing effective prevention strategies.