title: Altered metabolism of gut microbiota contributes to chronic immune activation in HIV-infected individuals.
abstract: 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.
authors.affiliation: 1] Unidad Mixta de Investigación en Genómica y Salud de la Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunidad Valenciana (FISABIO-Salud Pública) y el Instituto Cavanilles de Biodiversitad y Biología Evolutiva (Universitat de València), Valencia, Spain [2] CIBER on Epidemiology and Public Health (CIBERESP), Madrid, Spain.
authors.forename: J F
authors.initials: JF
authors.lastname: Vázquez-Castellanos
authors.affiliation: Department of Infectious Diseases, University Hospital Ramón y Cajal-IRYCIS, Madrid, Spain.
authors.forename: S
authors.initials: S
authors.lastname: Serrano-Villar
authors.affiliation: 1] Unidad Mixta de Investigación en Genómica y Salud de la Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunidad Valenciana (FISABIO-Salud Pública) y el Instituto Cavanilles de Biodiversitad y Biología Evolutiva (Universitat de València), Valencia, Spain [2] CIBER on Epidemiology and Public Health (CIBERESP), Madrid, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Latorre
authors.affiliation: Unidad Mixta de Investigación en Genómica y Salud de la Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunidad Valenciana (FISABIO-Salud Pública) y el Instituto Cavanilles de Biodiversitad y Biología Evolutiva (Universitat de València), Valencia, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Artacho
authors.affiliation: Unidad Mixta de Investigación en Genómica y Salud de la Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunidad Valenciana (FISABIO-Salud Pública) y el Instituto Cavanilles de Biodiversitad y Biología Evolutiva (Universitat de València), Valencia, Spain.
authors.forename: M L
authors.initials: ML
authors.lastname: Ferrús
authors.affiliation: Department of Infectious Diseases, University Hospital Ramón y Cajal-IRYCIS, Madrid, Spain.
authors.forename: N
authors.initials: N
authors.lastname: Madrid
authors.affiliation: Department of Infectious Diseases, University Hospital Ramón y Cajal-IRYCIS, Madrid, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Vallejo
authors.affiliation: 1] Laboratory of Molecular Immune Biology, University Hospital Gregorio Marañón and Gregorio Marañón Research Institute, Madrid, Spain [2] CIBER on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid, Spain.
authors.forename: T
authors.initials: T
authors.lastname: Sainz
authors.affiliation: 1] Department of Biochemistry, University Hospital Ramón y Cajal-IRYCIS, Madrid, Spain [2] CIBER on Obesity and Nutrition Pathophysiology (CIBEROBN), Madrid, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Martínez-Botas
authors.affiliation: 1] Laboratory of Molecular Immune Biology, University Hospital Gregorio Marañón and Gregorio Marañón Research Institute, Madrid, Spain [2] CIBER on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid, Spain [3] Laboratory of Immunovirology, Department of Infectious Diseases, Biomedicine Institute of Seville (IBIS), University Hospital Virgen del Rocío, Sevilla, Spain.
authors.forename: S
authors.initials: S
authors.lastname: Ferrando-Martínez
authors.affiliation: Centro Sandoval, Madrid, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Vera
authors.affiliation: Department of Infectious Diseases, University Hospital Ramón y Cajal-IRYCIS, Madrid, Spain.
authors.forename: F
authors.initials: F
authors.lastname: Dronda
authors.affiliation: Laboratory of Immunovirology, Department of Infectious Diseases, Biomedicine Institute of Seville (IBIS), University Hospital Virgen del Rocío, Sevilla, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Leal
authors.affiliation: Centro Sandoval, Madrid, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Del Romero
authors.affiliation: Department of Infectious Diseases, University Hospital Ramón y Cajal-IRYCIS, Madrid, Spain.
authors.forename: S
authors.initials: S
authors.lastname: Moreno
authors.affiliation: HIV Unit, Department of Internal Medicine, University Hospital Clínico San Carlos, Madrid, Spain.
authors.forename: V
authors.initials: V
authors.lastname: Estrada
authors.affiliation: 1] Unidad Mixta de Investigación en Genómica y Salud de la Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunidad Valenciana (FISABIO-Salud Pública) y el Instituto Cavanilles de Biodiversitad y Biología Evolutiva (Universitat de València), Valencia, Spain [2] CIBER on Epidemiology and Public Health (CIBERESP), Madrid, Spain.
authors.forename: M J
authors.initials: MJ
authors.lastname: Gosalbes
authors.affiliation: 1] Unidad Mixta de Investigación en Genómica y Salud de la Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunidad Valenciana (FISABIO-Salud Pública) y el Instituto Cavanilles de Biodiversitad y Biología Evolutiva (Universitat de València), Valencia, Spain [2] CIBER on Epidemiology and Public Health (CIBERESP), Madrid, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Moya
mesh_terms: D056704:Adaptive Immunity; D023241:Antiretroviral Therapy, Highly Active; D001499:Bayes Theorem; D044822:Biodiversity; D016022:Case-Control Studies; D016000:Cluster Analysis; D018450:Disease Progression; D000069196:Gastrointestinal Microbiome; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D008390:Markov Chains; D055442:Metabolome; D055432:Metabolomics; D054892:Metagenome; D012336:RNA, Ribosomal, 16S
chemical_list: D012336:RNA, Ribosomal, 16S