title: An altered intestinal mucosal microbiome in HIV-1 infection is associated with mucosal and systemic immune activation and endotoxemia.
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.
authors.affiliation: Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
authors.forename: S M
authors.initials: SM
authors.lastname: Dillon
authors.affiliation: Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
authors.forename: E J
authors.initials: EJ
authors.lastname: Lee
authors.affiliation: Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
authors.forename: C V
authors.initials: CV
authors.lastname: Kotter
authors.affiliation: Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
authors.forename: G L
authors.initials: GL
authors.lastname: Austin
authors.affiliation: Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
authors.forename: Z
authors.initials: Z
authors.lastname: Dong
authors.affiliation: Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
authors.forename: D K
authors.initials: DK
authors.lastname: Hecht
authors.affiliation: Department of Medicine, University of California, San Diego, La Jolla, California, USA.
authors.forename: S
authors.initials: S
authors.lastname: Gianella
authors.affiliation: Department of Immunology-Microbiology, Rush University Medical Center, Chicago, Illinois, USA.
authors.forename: B
authors.initials: B
authors.lastname: Siewe
authors.affiliation: Department of Medicine, University of California, San Diego, La Jolla, California, USA.
authors.forename: D M
authors.initials: DM
authors.lastname: Smith
authors.affiliation: Department of Immunology-Microbiology, Rush University Medical Center, Chicago, Illinois, USA.
authors.forename: A L
authors.initials: AL
authors.lastname: Landay
authors.affiliation: Department of Molecular, Cellular and Developmental Biology, University of Colorado Boulder, Boulder, Colorado, USA.
authors.forename: C E
authors.initials: CE
authors.lastname: Robertson
authors.affiliation: 1] Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA [2] University of Colorado Microbiome Research Consortium, Aurora, Colorado, USA.
authors.forename: D N
authors.initials: DN
authors.lastname: Frank
authors.affiliation: Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
authors.forename: C C
authors.initials: CC
authors.lastname: Wilson
mesh_terms: D000328:Adult; D044822:Biodiversity; D001706:Biopsy; D015992:Body Mass Index; D018791:CD4 Lymphocyte Count; D003106:Colon / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D004032:Diet; D064806:Dysbiosis / Q000276:immunology; D019446:Endotoxemia / Q000276:immunology*; D005260:Female; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007109:Immunity; D007413:Intestinal Mucosa / Q000276:immunology* / Q000382:microbiology* / Q000473:pathology; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D064307:Microbiota; D008875:Middle Aged; D016176:T-Lymphocyte Subsets / Q000276:immunology; D019562:Viral Load; D055815:Young Adult