Altered metabolism of gut microbiota contributes to chronic immune activation in HIV-infected individuals

Altered interplay between gut mucosa and microbiota during treated HIV infection may possibly contribute to increased bacterial translocation and chronic immune activation, both of which are predictors of morbidity and mortality. Although a dysbiotic gut microbiota has recently been reported in HIV+...

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Published in:Mucosal immunology 2015-07, Vol.8 (4), p.760-772
Main Authors: Vázquez-Castellanos, J F, Serrano-Villar, S, Latorre, A, Artacho, A, Ferrús, M L, Madrid, N, Vallejo, A, Sainz, T, Martínez-Botas, J, Ferrando-Martínez, S, Vera, M, Dronda, F, Leal, M, Del Romero, J, Moreno, S, Estrada, V, Gosalbes, M J, Moya, A
Format: Article
Language:English
Subjects:
Adaptive Immunity
Antiretroviral Therapy, Highly Active
Bayes Theorem
Biodiversity
Case-Control Studies
Cluster Analysis
Disease Progression
Gastrointestinal Microbiome
HIV Infections - drug therapy
HIV Infections - immunology
HIV Infections - metabolism
HIV Infections - microbiology
HIV-1 - immunology
Humans
Immunity, Innate
Markov Chains
Metabolome
Metabolomics
Metagenome
RNA, Ribosomal, 16S
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Summary:Altered interplay between gut mucosa and microbiota during treated HIV infection may possibly contribute to increased bacterial translocation and chronic immune activation, both of which are predictors of morbidity and mortality. Although a dysbiotic gut microbiota has recently been reported in HIV+ individuals, the metagenome gene pool associated with HIV infection remains unknown. The aim of this study is to characterize the functional gene content of gut microbiota in HIV+ patients and to define the metabolic pathways of this bacterial community, which is potentially associated with immune dysfunction. We determined systemic markers of innate and adaptive immunity in a cohort of HIV-infected individuals on successful antiretroviral therapy without comorbidities and in healthy non-HIV-infected subjects. Metagenome sequencing revealed an altered functional profile, with enrichment of the genes involved in various pathogenic processes, lipopolysaccharide biosynthesis, bacterial translocation, and other inflammatory pathways. In contrast, we observed depletion of genes involved in amino acid metabolism and energy processes. Bayesian networks showed significant interactions between the bacterial community, their altered metabolic pathways, and systemic markers of immune dysfunction. This study reveals altered metabolic activity of microbiota and provides novel insight into the potential host-microbiota interactions driving the sustained inflammatory state in successfully treated HIV-infected patients.
ISSN:1933-0219
1935-3456
DOI:10.1038/mi.2014.107