4.7 Article

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

Journal

JOURNAL OF INFECTIOUS DISEASES
Volume 211, Issue 1, Pages 19-27

Publisher

OXFORD UNIV PRESS INC
DOI: 10.1093/infdis/jiu409

Keywords

HIV; microbiota; dysbiosis; inflammation; microbial translocation

Funding

  1. National Institutes of Health (NIH) [RO1 HL096585, RO1 HL6594, T32 AI07389, T32AI007438]
  2. Lifespan/Tufts/Brown Center for AIDS Research (NIH) [P30AI042853]
  3. Tufts Nutrition Collaborative-Center for Drug Abuse and AIDS Research (NIH) [P30DA013868]
  4. Tufts Clinical and Translational Science Institute (NIH) [UL1 TR000073]

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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.

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