Microbial translocation and microbiome dysbiosis in HIV-associated immune activation

Abstract

Purpose of review: This article describes the mechanisms and consequences of both microbial translocation and microbial dysbiosis in HIV infection.

Recent findings: Microbes in HIV are likely playing a large role in contributing to HIV pathogenesis, morbidities and mortality. Two major disruptions to microbial systems in HIV infection include microbial translocation and microbiome dysbiosis. Microbial translocation occurs when the bacteria (or bacterial products) that should be in the lumen of the intestine translocate across the tight epithelial barrier into systemic circulation, where they contribute to inflammation and pathogenesis. This is associated with poorer health outcomes in HIV-infected individuals. In addition, microbial populations in the gastrointestinal tract are also altered after HIV infection, resulting in microbiome dysbiosis, which further exacerbates microbial translocation, epithelial barrier disruption, inflammation and mucosal immune functioning.

Summary: Altered microbial regulation in HIV infection can lead to poor health outcomes, and understanding the mechanisms underlying microbial dysbiosis and translocation may result in novel pathways for therapeutic interventions.

Figure 1

Microbial dysbiosis in HIV is characterized by decreased abundances of Bacteroides, Lactobacillus, and beneficial Clostridia with increased abundances of Prevotella and pathogenic Proteobacteria, increasing T cell and DC activation. Loss of secretory IgA may help to explain the outgrowth of pathogenic bacteria. Increased neutrophil and macrophage accumulation in the LP, bacterial activity in the mucosa, and other mechanisms destabilize the mucosa and GI epithelium, leading to MT and further accumulation of inflammatory microbial products and cytokines in circulation. Together, these mechanisms perpetuate an inflammatory cycle that leads to chronic immune activation in ART treated HIV-infected individuals.