754. Expanded Enteric Virome and Altered Bacterial Microbiome in AIDS
Session: Poster Abstract Session: All Things Microbiome
Friday, October 9, 2015
Room: Poster Hall
Background: HIV infects an estimated 35 million adults globally. A hallmark of HIV disease is the rapid depletion of CD4+ T cells in the gut-associated lymphoid tissue and increased translocation of microbial products through this compromised epithelial barrier. Prior work in our laboratory demonstrated expansion of the enteric eukaryotic virome, or viral microbiome, during pathogenic simian immunodeficiency virus infection of macaques, while the bacterial microbiome remained unchanged, suggesting that alterations in the enteric virome may be important in the pathogenesis of AIDS. In humans, the effect of HIV on the enteric virome and bacterial microbiome is incompletely characterized. 

Methods: Here we use next-generation sequencing techniques (16S ribosomal RNA and Illumina Miseq shotgun sequencing) to analyze the enteric microbiome in stool from a Ugandan cohort of 40 HIV-negative patients, 40 HIV-infected patients on antiretroviral therapy, and 42 HIV-infected, treatment-naïve patients. 

Results: In subjects with CD4+ T cell counts less than 200 cells/ml we noted an expansion of adenoviruses and anelloviruses. In contrast, enteric bacterial diversity was decreased in subjects with AIDS, and Enterobacteriaceae family members, previously linked to gut inflammation, were increased. Peripheral CD4+ T cell counts negatively correlated with circulating levels of soluble CD14, a bacterial LPS binding protein, suggesting increased translocation of pro-inflammatory microbial products with increasing immunodeficiency. 

Conclusion: We show that advanced HIV disease is associated with dysbiosis of the enteric virome and bacterial microbiome. These alterations may contribute to AIDS-associated enteropathy and the systemic inflammation accompanying progression to AIDS. Immune reconstitution may restore balance to the enteric microbiome.

Cynthia Monaco, M.D., Ph.D.1, David Gootenberg, B.A.2, Guoyan Zhao, Ph.D.3, Efrem Lim, Ph.D.4, Musie Ghebremichael, Ph.D.2, Megan Baldridge, M.D., Ph.D.3, Craig Wilen, M.D., Ph.D.3, Scott Handley, Ph.D.3, Meaghan Flagg, B.S.2, Mark Siedner, M.D. M.P.H.5, Jason Norman, Ph.D.3, Brian Keller, M.D., Ph.D.1, Alexander Lankowski, M.A.5, David Wang, Ph.D.4, Douglas Kwon, M.D., Ph.D.2 and Herbert Virgin, M.D., Ph.D.3, (1)Department of Medicine, Washington University School of Medicine, St. Louis, MO, (2)Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, (3)Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, (4)Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, (5)Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA

Disclosures:

C. Monaco, None

D. Gootenberg, None

G. Zhao, None

E. Lim, None

M. Ghebremichael, None

M. Baldridge, None

C. Wilen, None

S. Handley, None

M. Flagg, None

M. Siedner, None

J. Norman, None

B. Keller, None

A. Lankowski, None

D. Wang, None

D. Kwon, None

H. Virgin, None

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