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

被引:386
作者
Dillon, S. M. [1 ]
Lee, E. J. [1 ]
Kotter, C. V. [1 ]
Austin, G. L. [1 ]
Dong, Z. [1 ]
Hecht, D. K. [1 ]
Gianella, S. [2 ]
Siewe, B. [3 ]
Smith, D. M. [2 ]
Landay, A. L. [3 ]
Robertson, C. E. [4 ]
Frank, D. N. [1 ,5 ]
Wilson, C. C. [1 ]
机构
[1] Univ Colorado, Dept Med, Aurora, CO 80045 USA
[2] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA
[3] Rush Univ, Med Ctr, Dept Immunol & Microbiol, Chicago, IL 60612 USA
[4] Univ Colorado, Dept Mol Cellular & Dev Biol, Boulder, CO 80309 USA
[5] Univ Colorado, Microbiome Res Consortium, Aurora, CO USA
基金
美国国家卫生研究院;
关键词
T-CELL DEPLETION; DENDRITIC CELLS; TRANSLOCATION; METABOLISM; BARRIER; SOFTWARE; BUTYRATE; BACTERIA; PRIMERS; DRIVEN;
D O I
10.1038/mi.2013.116
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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 Tcells 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.
引用
收藏
页码:983 / 994
页数:12
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