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Open Access Research

HIV Infection is associated with compositional and functional shifts in the rectal mucosal microbiota

Ian H McHardy1, Xiaoxiao Li2, Maomeng Tong3, Paul Ruegger4, Jonathan Jacobs15, James Borneman4, Peter Anton56 and Jonathan Braun1*

Author Affiliations

1 Pathology and Laboratory Medicine, UCLA, 10833 Le Conte Ave 13-188 CHS, Los Angeles, CA 90095, USA

2 Inflammatory Bowel Disease & Immunobiology Research Institute, Cedars Sinai Medical Center, Los Angeles 90048, USA

3 Pharmacology, UCLA, Los Angeles, CA, USA

4 Plant Pathology, UC Riverside, Riverside, CA, USA

5 Department of Medicine, UCLA, Los Angeles, CA, USA

6 Center for HIV Prevention Research, UCLA AIDS Institute, Los Angeles, CA, USA

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Microbiome 2013, 1:26  doi:10.1186/2049-2618-1-26

Published: 12 October 2013

Abstract

Background

Regardless of infection route, the intestine is the primary site for HIV-1 infection establishment and results in significant mucosal CD4+ T lymphocyte depletion, induces an inflammatory state that propagates viral dissemination, facilitates microbial translocation, and fosters establishment of one of the largest HIV reservoirs. Here we test the prediction that HIV infection modifies the composition and function of the mucosal commensal microbiota.

Results

Rectal mucosal microbiota were collected from human subjects using a sponge-based sampling methodology. Samples were collected from 20 HIV-positive men not receiving combination anti-retroviral therapy (cART), 20 HIV-positive men on cART and 20 healthy, HIV-negative men. Microbial composition of samples was analyzed using barcoded 16S Illumina deep sequencing (85,900 reads per sample after processing). Microbial metagenomic information for the samples was imputed using the bioinformatic tools PICRUST and HUMAnN. Microbial composition and imputed function in HIV-positive individuals not receiving cART was significantly different from HIV-negative individuals. Genera including Roseburia, Coprococcus, Ruminococcus, Eubacterium, Alistipes and Lachnospira were depleted in HIV-infected subjects not receiving cART, while Fusobacteria, Anaerococcus, Peptostreptococcus and Porphyromonas were significantly enriched. HIV-positive subjects receiving cART exhibited similar depletion and enrichment for these genera, but were of intermediate magnitude and did not achieve statistical significance. Imputed metagenomic functions, including amino acid metabolism, vitamin biosynthesis, and siderophore biosynthesis differed significantly between healthy controls and HIV-infected subjects not receiving cART.

Conclusions

HIV infection was associated with rectal mucosal changes in microbiota composition and imputed function that cART failed to completely reverse. HIV infection was associated with depletion of some commensal species and enrichment of a few opportunistic pathogens. Many imputed metagenomic functions differed between samples from HIV-negative and HIV-positive subjects not receiving cART, possibly reflecting mucosal metabolic changes associated with HIV infection. Such functional pathways may represent novel interventional targets for HIV therapy if normalizing the microbial composition or functional activity of the microbiota proves therapeutically useful.

Keywords:
HIV; Microbiome; Metagenome; Mucosa