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PMID: 24399150 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

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

Mucosal immunology ·Vol. 7 ·No. 4 ·2014-07-00 ·Pages 983-94

Dillon SM, Lee EJ, Kotter CV, Austin GL, Dong Z, Hecht DK, Gianella S, Siewe B, Smith DM, Landay AL, Robertson CE, Frank DN, Wilson CC

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.

MeSH Terms
Adult Biodiversity Biopsy Body Mass Index CD4 Lymphocyte Count Colon/immunology,microbiology,pathology Diet Dysbiosis/immunology Endotoxemia/immunology Female HIV Infections/immunology,virology HIV-1/immunology Humans Immunity Intestinal Mucosa/immunology,microbiology,pathology Lymphocyte Activation/immunology Male Microbiota Middle Aged T-Lymphocyte Subsets/immunology Viral Load Young Adult
Authors & Affiliations
13 authors, click to expand affiliations / ORCID
Dillon S M
Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
Lee E J
Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
Kotter C V
Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
Austin G L
Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
Dong Z
Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
Hecht D K
Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
Gianella S
Department of Medicine, University of California, San Diego, La Jolla, California, USA.
Siewe B
Department of Immunology-Microbiology, Rush University Medical Center, Chicago, Illinois, USA.
Smith D M
Department of Medicine, University of California, San Diego, La Jolla, California, USA.
Landay A L
Department of Immunology-Microbiology, Rush University Medical Center, Chicago, Illinois, USA.
Robertson C E
Department of Molecular, Cellular and Developmental Biology, University of Colorado Boulder, Boulder, Colorado, USA.
Frank D N
1] Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA [2] University of Colorado Microbiome Research Consortium, Aurora, Colorado, USA.
Wilson C C
Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
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Article Info
Journal
Mucosal immunology
Abbr.
Mucosal Immunol
ISSN
1935-3456
DOI
10.1038/mi.2013.116
Published
2014-07-00
Epub
2014-00-08
Pages
983-94
Language
English
Region
United States
NLM ID
101299742
PMCID
PMC4062575
Subset
IM
Grants
NIDDK NIH HHS · R01 DK088663 · United States
NIAID NIH HHS · R01 AI108404 · United States
NIDDK NIH HHS · 1R01 DK088663 · United States
NIAID NIH HHS · AI36214 · United States
NCATS NIH HHS · UL1 TR000154 · United States
NIAID NIH HHS · P30 AI036214 · United States
NCATS NIH HHS · UL1 TR001082 · United States
External Links
PubMed source DOI: 10.1038/mi.2013.116 PMC Full Text View journal details
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