Intestinal microbiota, microbial translocation, and systemic inflammation in chronic HIV infection

Abstract

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 1β (IL-1β) level; the relative abundances of Enterobacteriales and Enterobacteriaceae and the interferon γ level; and the relative abundances of Erysipelotrichi and Barnesiella and the TNF-α level. There were negative correlations between endotoxin core IgM and IL-1β 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.

Keywords: HIV; dysbiosis; inflammation; microbial translocation; microbiota.

Figure 1.

Stool microbial community composition in cases, compared with that in controls. Community composition dissimilarity was analyzed using nonmetric dimensional scaling (NMDS) based on a Canberra community dissimilarity matrix. Each dot represents the microbiota of a single subject. Ellipses represent 95% confidence intervals for the standard error of weighted NDMS score means of cases and controls. Community differences were verified using Adonis (P = <.05).

Figure 2.

Relative abundance of major phyla in cases (+) and controls (−). In both groups, the 2 dominant phyla were Bacteroidetes and Firmicutes, which made up >95% of each individual's microbiota, with the exception of case 9, who had an unusually high relative abundance of fusobacteria in lieu of Firmicutes.

Figure 3.

Linear discriminant analysis (LDA) effect size (LEfSe) detects specific differentially abundant taxa in cases and controls. A, Cladogram showing differentially abundant taxonomic clades with an LDA score >2.0 among cases and controls. B, LDA scores of differentially abundant taxa among cases and controls. The LDA score indicates the effect size and ranking of each differentially abundant taxon. C, The relative abundance of taxa identified by LEfSe as being differentially abundant in cases and controls was compared using the Mann–Whitney test: Proteobacteria, P = <.05; Gammaproteobacteria, P = .04; Enterobacteriales, P = <.05; Enterobacteriaceae, P = <.05; Erysipelotrichi, P = .01; Erysipelotrichales, P = .01; Erysipelotrichaceae, P = .01; Barnesiella, P = .01; Alistipes, P = .01; and Rikenellaceae, P = .01.

Figure 4.

Markers of microbial translocation and systemic inflammation in cases and controls. Levels of markers of microbial translocation (soluble CD14 [sCD14], endotoxin core antibody [EndoCAb], 16S ribosomal RNA [rRNA] gene, and lipopolysaccharide [LPS]) and systemic inflammation (interleukin 6 [IL-6], interferon γ [IFN-γ], interleukin 1β [IL-1β], tumor necrosis factor α [TNF-α], and high-sensitivity C-reactive protein [hsCRP]) were measured in cases and controls, as described in “Methods” section, and compared using the Mann–Whitney test. *P = <.01.