The gut microbiome and HIV-1 pathogenesis

Abstract

HIV-1 infection is associated with substantial damage to the gastrointestinal (GI) 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.

Effect of cytomegalovirus and Epstein–Barr virus replication on intestinal mucosal gene expression and microbiome composition of HIV-infected and uninfected individuals

“…Recent studies described the effect of HIV-infection on the composition of the gut microbiome [8–10], and on the mucosal gene expression profile [11]. HIV-infection is associated with decreased diversity of the host intestinal microbiome, and “dysbiosis” which is characterized by a loss of bacterial taxa that are typically considered commensal (i.e., Lactobacilli and Bifidobacteria) with an increase in pathogenic bacteria (i.e., Pseudomonas and Proteobacteria) [8, 9].…”

Brief Report: Inflammatory Colonic Innate Lymphoid Cells Are Increased During Untreated HIV-1 Infection and Associated With Markers of Gut Dysbiosis and Mucosal Immune Activation

“…We, and others, have demonstrated that alterations in intestinal mucosa-associated bacterial communities during HIV-1 infection are associated with indicators of mucosal HIV-1 pathogenesis (reviewed in 40 ). In our study, major findings from the microbiome analysis included higher relative abundance of mucosa-associated bacteria belonging to the Proteobacteria phylum (including Xanthomonadaceae) and of Prevotella spp .…”

Incomplete immune reconstitution in HIV/AIDS patients on antiretroviral therapy: Challenges of immunological non-responders

“…In the early stage of HIV‐1 infection, massive amounts of CD4 + T cells in the gut are depleted, especially T helper (Th) 17 cells and Th22 cells, which play an important role in maintaining the integrity of the gut. HIV‐1 infection is also associated with gut epithelial barrier damage characterized by villous atrophy, enterocyte apoptosis, crypt hyperplasia, decreased expression of tight junction proteins, and increased gastrointestinal inflammation, which contributes to increased intestinal permeability . These abnormalities eventually result in alteration of the intestinal microbiota composition (dysbiosis) and release of bacterial products into the circulation (microbial translocation), leading to chronic immune activation and inflammation .…”

“…These studies suggest that microbial product translocation from the gut to the circulation was associated with immune activation and imply CD4 + T‐cell depletion during suppressive ART treatment. HIV‐1 infection is associated with a decrease in intestinal microbial diversity . Nowak et al.…”