The gut microbiome and HIV-1 pathogenesis: a two-way street

Abstract

HIV-1 infection is associated with substantial damage to the gastrointestinal tract resulting in structural impairment of the epithelial barrier and a disruption of intestinal homeostasis. The accompanying translocation of microbial products and potentially microbes themselves from the lumen into systemic circulation has been linked to immune activation, inflammation, and HIV-1 disease progression. The importance of microbial translocation in the setting of HIV-1 infection has led to a recent focus on understanding how the communities of microbes that make up the intestinal microbiome are altered during HIV-1 infection and how they interact with mucosal immune cells to contribute to inflammation. This review details the dysbiotic intestinal communities associated with HIV-1 infection and their potential link to HIV-1 pathogenesis. We detail studies that begin to address the mechanisms driving microbiota-associated immune activation and inflammation and the various treatment strategies aimed at correcting dysbiosis and improving the overall health of HIV-1-infected individuals. Finally, we discuss how this relatively new field of research can advance to provide a more comprehensive understanding of the contribution of the gut microbiome to HIV-1 pathogenesis.

Figure 1

HIV-1 infection is associated with alterations in the intestinal microbiome including changes in both diversity and composition (1). Dysbiosis is typically characterized by decreased abundances of bacteria important in maintaining epithelial barrier health and in immuneregulation in combination with increased abundance of bacteria with pro-inflammatory potential (pathobionts). Translocation of pathobionts through the disrupted epithelial barrier (2) leads to activation of innate immune cells (3). Activated innate immune cells not only contribute to local inflammation (4), but activated myeloid dendritic cells (mDC) drive increased T cell activation and expansion leading to increased infection and death and a loss of protective Th17 and Th22 cells (5). Increased T cell activation, in conjunction with a lack of protective Th cells further contributes to the inflammatory environment (6) which potentiates epithelial barrier breakdown (leading to increased microbial translocation) and may promote dysbiosis (7). In addition to mucosal inflammation and the breakdown in intestinal homeostasis, other factors such as diet, sexual behaviour and anti-retroviral therapy (ART) may also contribute to alterations in the intestinal microbiome (8). Ultimately, the combined effect of dysbiosis, microbial translocation and mucosal inflammation lead to chronic generalized immune activation, systemic inflammation and associated co-morbidities.

Figure 2

Future Research Directions to Investigate the Relationship Between the Gut Microbiome and HIV-1 Pathogenesis.