Intestinal Microbiota, Microbial Translocation, and Systemic Inflammation in Chronic HIV Infection

被引:383
作者
Dinh, Duy M. [1 ]
Volpe, Gretchen E. [1 ,2 ]
Duffalo, Chad [1 ]
Bhalchandra, Seema [1 ]
Tai, Albert K. [3 ]
Kane, Anne V. [1 ]
Wanke, Christine A. [1 ,2 ]
Ward, Honorine D. [1 ,2 ]
机构
[1] Tufts Med Ctr, Div Geog Med & Infect Dis, Boston, MA 02111 USA
[2] Tufts Univ, Sch Med, Dept Publ Hlth & Community Med, Boston, MA 02111 USA
[3] Tufts Univ, Sch Med, Dept Integrat Physiol & Pathobiol, Boston, MA 02111 USA
基金
美国国家卫生研究院;
关键词
HIV; microbiota; dysbiosis; inflammation; microbial translocation; IMMUNE ACTIVATION; GUT MICROBIOTA; DISEASE PROGRESSION; CROHNS-DISEASE; LIPOPOLYSACCHARIDE; PATHOGENESIS; MAGNITUDE; DISCOVERY; SEQUENCES; THERAPY;
D O I
10.1093/infdis/jiu409
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Background. Despite effective antiretroviral therapy (ART), patients with chronic human immunodeficiency virus (HIV) infection have increased microbial translocation and systemic inflammation. Alterations in the intestinal microbiota may play a role in microbial translocation and inflammation. Methods. We profiled the fecal microbiota by pyrosequencing the gene encoding 16S ribosomal RNA (rRNA) and measured markers of microbial translocation and systemic inflammation in 21 patients who had chronic HIV infection and were receiving suppressive ART (cases) and 16 HIV-uninfected controls. Results. The fecal microbial community composition was significantly different between cases and controls. The relative abundance of Proteobacteria, Gammaproteobacteria, Enterobacteriales, Enterobacteriaceae, Erysipelotrichi, Erysipelotrichales, Erysipelotrichaceae, and Barnesiella was significantly enriched in cases, whereas that of Rikenellaceae and Alistipes was depleted. The plasma soluble CD14 level (sCD14) was significantly higher and the endotoxin core immunoglobulin M (IgM) level lower in cases, compared with controls. There were significant positive correlations between the relative abundances of Enterobacteriales and Enterobacteriaceae and the sCD14 level; the relative abundances of Gammaproteobacteria, Enterobacteriales, and Enterobacteriaceae and the interleukin 1 beta (IL-1 beta) level; the relative abundances of Enterobacteriales and Enterobacteriaceae and the interferon gamma level; and the relative abundances of Erysipelotrichi and Barnesiella and the TNF-alpha level. There were negative correlations between endotoxin core IgM and IL-1 beta levels. Conclusions. Patients who have chronic HIV infection and are receiving suppressive ART display intestinal dysbiosis associated with increased microbial translocation and significant associations between specific taxa and markers of microbial translocation and systemic inflammation. This was an exploratory study, the findings of which need to be confirmed.
引用
收藏
页码:19 / 27
页数:9
相关论文
共 48 条
[1]   Human immunodeficiency virus-related microbial translocation and progression of hepatitis C [J].
Balagopal, Ashwin ;
Philp, Frances H. ;
Astemborski, Jacquie ;
Block, Timothy M. ;
Mehta, Anand ;
Long, Ronald ;
Kirk, Gregory D. ;
Mehta, Shruti H. ;
Cox, Andrea L. ;
Thomas, David L. ;
Ray, Stuart C. .
GASTROENTEROLOGY, 2008, 135 (01) :226-233
[2]   Microbial translocation is a cause of systemic immune activation in chronic HIV infection [J].
Brenchley, Jason M. ;
Price, David A. ;
Schacker, Timothy W. ;
Asher, Tedi E. ;
Silvestri, Guido ;
Rao, Srinivas ;
Kazzaz, Zachary ;
Bornstein, Ethan ;
Lambotte, Olivier ;
Altmann, Daniel ;
Blazar, Bruce R. ;
Rodriguez, Benigno ;
Teixeira-Johnson, Leia ;
Landay, Alan ;
Martin, Jeffrey N. ;
Hecht, Frederick M. ;
Picker, Louis J. ;
Lederman, Michael M. ;
Deeks, Steven G. ;
Douek, Daniel C. .
NATURE MEDICINE, 2006, 12 (12) :1365-1371
[3]   Microbial Translocation Across the GI Tract [J].
Brenchley, Jason M. ;
Douek, Daniel C. .
ANNUAL REVIEW OF IMMUNOLOGY, VOL 30, 2012, 30 :149-173
[4]   QIIME allows analysis of high-throughput community sequencing data [J].
Caporaso, J. Gregory ;
Kuczynski, Justin ;
Stombaugh, Jesse ;
Bittinger, Kyle ;
Bushman, Frederic D. ;
Costello, Elizabeth K. ;
Fierer, Noah ;
Pena, Antonio Gonzalez ;
Goodrich, Julia K. ;
Gordon, Jeffrey I. ;
Huttley, Gavin A. ;
Kelley, Scott T. ;
Knights, Dan ;
Koenig, Jeremy E. ;
Ley, Ruth E. ;
Lozupone, Catherine A. ;
McDonald, Daniel ;
Muegge, Brian D. ;
Pirrung, Meg ;
Reeder, Jens ;
Sevinsky, Joel R. ;
Tumbaugh, Peter J. ;
Walters, William A. ;
Widmann, Jeremy ;
Yatsunenko, Tanya ;
Zaneveld, Jesse ;
Knight, Rob .
NATURE METHODS, 2010, 7 (05) :335-336
[5]   PyNAST: a flexible tool for aligning sequences to a template alignment [J].
Caporaso, J. Gregory ;
Bittinger, Kyle ;
Bushman, Frederic D. ;
DeSantis, Todd Z. ;
Andersen, Gary L. ;
Knight, Rob .
BIOINFORMATICS, 2010, 26 (02) :266-267
[6]  
Cooley PC, 1998, COMPUT HUM BEHAV, V14, P195, DOI 10.1016/S0747-5632(98)00001-6
[7]   Guidelines for managing cardiovascular risk: an evolving area [J].
Currier, Judith S. ;
Lundgren, Jens D. .
CURRENT OPINION IN HIV AND AIDS, 2008, 3 (03) :205-206
[8]   HIV How to escape treatment [J].
Deeks, Steven G. .
NATURE, 2011, 477 (7362) :36-37
[9]   An altered intestinal mucosal microbiome in HIV-1 infection is associated with mucosal and systemic immune activation and endotoxemia [J].
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. .
MUCOSAL IMMUNOLOGY, 2014, 7 (04) :983-994
[10]   Search and clustering orders of magnitude faster than BLAST [J].
Edgar, Robert C. .
BIOINFORMATICS, 2010, 26 (19) :2460-2461