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

Mucosal Immunol. 2014 Jul;7(4):983-94. doi: 10.1038/mi.2013.116. Epub 2014 Jan 8.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Biodiversity
  • Biopsy
  • Body Mass Index
  • CD4 Lymphocyte Count
  • Colon / immunology
  • Colon / microbiology
  • Colon / pathology
  • Diet
  • Dysbiosis / immunology
  • Endotoxemia / immunology*
  • Female
  • HIV Infections / immunology*
  • HIV Infections / virology
  • HIV-1 / immunology*
  • Humans
  • Immunity*
  • Intestinal Mucosa / immunology*
  • Intestinal Mucosa / microbiology*
  • Intestinal Mucosa / pathology
  • Lymphocyte Activation / immunology
  • Male
  • Microbiota*
  • Middle Aged
  • T-Lymphocyte Subsets / immunology
  • Viral Load
  • Young Adult