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

• Published in: Mucosal immunology Vol. 7; no. 4; pp. 983 - 994
• Main Authors: Dillon, S M, Lee, E J, Kotter, C V, Austin, G L, Dong, Z, Hecht, D K, Gianella, S, Siewe, B, Smith, D M, Landay, A L, Robertson, C E, Frank, D N, Wilson, C C
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01-07-2014; Elsevier Limited
• Subjects: 631/250/256/1980; 631/250/347; 692/698/2741/2135; 692/699/255/1901; Adult; Allergology; Antibodies; Biodiversity; Biomedical and Life Sciences; Biomedicine; Biopsy; Body Mass Index; CD4 Lymphocyte Count; Colon - immunology; Colon - microbiology; Colon - pathology; Diet; Dysbiosis - immunology; Endotoxemia - immunology; Female; Gastroenterology; HIV Infections - immunology; HIV Infections - virology; HIV-1 - immunology; Humans; Immunity; Immunology; Intestinal Mucosa - immunology; Intestinal Mucosa - microbiology; Intestinal Mucosa - pathology; Lymphocyte Activation - immunology; Male; Microbiota; Middle Aged; T-Lymphocyte Subsets - immunology; Viral Load; Young Adult
• ISSN: 1933-0219; 1935-3456
• DOI: 10.1038/mi.2013.116

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.