Research Article: A Compositional Look at the Human Gastrointestinal Microbiome and Immune Activation Parameters in HIV Infected Subjects

Date Published: February 20, 2014

Publisher: Public Library of Science

Author(s): Ece A. Mutlu, Ali Keshavarzian, John Losurdo, Garth Swanson, Basile Siewe, Christopher Forsyth, Audrey French, Patricia DeMarais, Yan Sun, Lars Koenig, Stephen Cox, Phillip Engen, Prachi Chakradeo, Rawan Abbasi, Annika Gorenz, Charles Burns, Alan Landay, David A. Relman.

http://doi.org/10.1371/journal.ppat.1003829

Abstract

HIV progression is characterized by immune activation and microbial translocation. One factor that may be contributing to HIV progression could be a dysbiotic microbiome. We therefore hypothesized that the GI mucosal microbiome is altered in HIV patients and this alteration correlates with immune activation in HIV. 121 specimens were collected from 21 HIV positive and 22 control human subjects during colonoscopy. The composition of the lower gastrointestinal tract mucosal and luminal bacterial microbiome was characterized using 16S rDNA pyrosequencing and was correlated to clinical parameters as well as immune activation and circulating bacterial products in HIV patients on ART. The composition of the HIV microbiome was significantly different than that of controls; it was less diverse in the right colon and terminal ileum, and was characterized by loss of bacterial taxa that are typically considered commensals. In HIV samples, there was a gain of some pathogenic bacterial taxa. This is the first report characterizing the terminal ileal and colonic mucosal microbiome in HIV patients with next generation sequencing. Limitations include use of HIV-infected subjects on HAART therapy.

Partial Text

Human immunodeficiency virus (HIV) infection is a chronic illness characterized by progressive CD4+ T cell loss. With the advent of highly active anti-retroviral therapy (HAART), HIV infection is controlled, resulting in reduced death from opportunistic infections. However, despite successful viral suppression, many HIV patients have persistent inflammation/immune activation resulting in the development of non-HIV comorbidities including cardiovascular disease, osteoporosis, neurocognitive decline, cancer, as well as increased mortality [1], [2].

This study represents a first global look at the lower GI tract microbiome in HIV-infected subjects using sequencing technologies. Our data shows that the lower intestinal mucosal bacterial populations in HIV-infected subjects are less diverse, definitely distinct from non-HIV controls, and composed more frequently of bacterial populations that are potentially pathogenic. Such disarray in the lower gut microbiome during HIV-infection goes along with findings of increased gut permeability in HIV and may be one of the contributing etiologic factors to HIV progression, warranting further investigation. Notably, the microbiome in HIV-infected subjects is so different that the cases can be distinctly separated from healthy controls based on global microbiome composition. In many other pyrosequencing experiments in human subjects, in unconstrained ordination analyses, the variability of the GI tract microbiome itself between subjects or samples, usually outweighs the effects seen as a result of disease. Such a large magnitude of disarray in the GI tract microbiome in HIV signals the importance of the GI tract microbiome in HIV infection, and could be both a consequence of HIV infection itself and/or a contributor to disease progression.

 

Source:

http://doi.org/10.1371/journal.ppat.1003829

 

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