Dysbiotic bacteria translocate in progressive SIV infection

Abstract

Infection of gut-resident CD4+ memory T-cells during acute HIV and SIV infection is associated with rapid loss of these cells and damage to the epithelial barrier. Damage to the epithelial barrier allows translocation of microbial products from the intestinal lumen into the body. Immune activation caused by these microbial products has been associated with disease progression. Although microbial translocation has been demonstrated in SIV-infected nonhuman primates, the identity of translocating bacteria has not been determined. In this study we examined the communities of bacteria both within the GI tract and systemic tissues of both healthy and experimentally SIV-infected Asian macaques. While there were only modest changes in the GI tract-associated microbiome resulting from infection, there is substantial dysbiosis after administration of antiretrovirals. Analysis of bacterial DNA isolated from tissues of infected animals revealed a preference for the phylum Proteobacteria, suggesting that they preferentially translocate. Consistent with this finding, we observed increased metabolic activity of Proteobacterial species within the colonic lumen of SIV-infected animals. Overall these data provide insights into disease progression and suggest that therapies aimed at altering the composition and metabolic activity of the GI tract microbiome could benefit chronically-HIV infected individuals particularly those on antiretroviral therapies.

Role of intestinal myofibroblasts in HIV-associated intestinal collagen deposition and immune reconstitution following combination antiretroviral therapy

“…In this report, we sought to examine the role of events at the interface of the gut mucosa and the systemic immune system to explore which factors influence peripheral CD4 + T-cell reconstitution following effective cART. We and others have previously demonstrated that higher percentages of proinflammatory bacterial taxa including the Proteobacteria/Enterobacteriales were associated with changes in the duodenal GALT T-cell subset proportions and T-cell activation [33, 60]. Similarly, Dillon et al .…”

Microbial translocation and microbiome dysbiosis in HIV-associated immune activation

“…One potential mechanism underlying damage to the epithelial barrier is alterations in the microbial communities of the GI tract. In HIV infection, there is an increased abundance of epithelial-adherent bacteria of the Proteobacteria family [38], and interestingly, it is this increased Proteobacteria that is found to predominantly translocate in SIV infection [39**]. This suggests that interactions between bacteria associated with the mucosa and the epithelium may contribute to MT.…”

Altered Virome and Bacterial Microbiome in Human Immunodeficiency Virus-Associated Acquired Immunodeficiency Syndrome

“…Antiretroviral therapy (ART) successfully controls systemic HIV replication but immune recovery is variable (Maartens et al, 2014). A hallmark of HIV disease is a rapid and profound depletion of CD4 T cells in the gut-associated lymphoid tissue (Brenchley et al, 2004; Klatt et al, 2008) and increased translocation of microbial products across this compromised epithelial barrier (Brenchley et al, 2006; Klase et al, 2015). HIV infection can also lead to enteropathy characterized by increased gastrointestinal (GI) inflammation, diarrhea and malabsorption (Brenchley, 2013).…”