Article

Mucosal Immunology (2014) 7, 983–994; doi:10.1038/mi.2013.116; published online 8 January 2014

An altered intestinal mucosal microbiome in HIV-1 infection is associated with mucosal and systemic immune activation and endotoxemia

S M Dillon1, E J Lee1, C V Kotter1, G L Austin1, Z Dong1, D K Hecht1, S Gianella2, B Siewe3, D M Smith2, A L Landay3, C E Robertson4, D N Frank1,5 and C C Wilson1

  1. 1Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
  2. 2Department of Medicine, University of California, San Diego, La Jolla, California, USA
  3. 3Department of Immunology-Microbiology, Rush University Medical Center, Chicago, Illinois, USA
  4. 4Department of Molecular, Cellular and Developmental Biology, University of Colorado Boulder, Boulder, Colorado, USA
  5. 5University of Colorado Microbiome Research Consortium, Aurora, Colorado, USA

Correspondence: CC Wilson, (cara.wilson@ucdenver.edu)

Received 9 October 2013; Revised 25 November 2013; Accepted 27 November 2013
Advance online publication 8 January 2014

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Abstract

Human immunodeficiency virus-1 (HIV-1) infection disrupts the intestinal immune system, leading to microbial translocation and systemic immune activation. We investigated the impact of HIV-1 infection on the intestinal microbiome and its association with mucosal T-cell and dendritic cell (DC) frequency and activation, as well as with levels of systemic T-cell activation, inflammation, and microbial translocation. Bacterial 16S ribosomal DNA sequencing was performed on colon biopsies and fecal samples from subjects with chronic, untreated HIV-1 infection and uninfected control subjects. Colon biopsies of HIV-1-infected subjects had increased abundances of Proteobacteria and decreased abundances of Firmicutes compared with uninfected donors. Furthermore at the genus level, a significant increase in Prevotella and decrease in Bacteroides was observed in HIV-1-infected subjects, indicating a disruption in the Bacteroidetes bacterial community structure. This HIV-1-associated increase in Prevotella abundance was associated with increased numbers of activated colonic T cells and myeloid DCs. Principal coordinates analysis demonstrated an HIV-1-related change in the microbiome that was associated with increased mucosal cellular immune activation, microbial translocation, and blood T-cell activation. These observations suggest that an important relationship exists between altered mucosal bacterial communities and intestinal inflammation during chronic HIV-1 infection.