title: Gut Bacteria Metabolism Impacts Immune Recovery in HIV-infected Individuals.
abstract: While changes in gut microbial populations have been described in human immuno-deficiency virus (HIV)-infected patients undergoing antiretroviral therapy (ART), the mechanisms underlying the contributions of gut bacteria and their molecular agents (metabolites and proteins) to immune recovery remain unexplored. To study this, we examined the active fraction of the gut microbiome, through examining protein synthesis and accumulation of metabolites inside gut bacteria and in the bloodstream, in 8 healthy controls and 29 HIV-infected individuals (6 being longitudinally studied). We found that HIV infection is associated to dramatic changes in the active set of gut bacteria simultaneously altering the metabolic outcomes. Effects were accentuated among immunological ART responders, regardless diet, subject characteristics, clinical variables other than immune recovery, the duration and type of ART and sexual preferences. The effect was found at quantitative levels of several molecular agents and active bacteria which were herein identified and whose abundance correlated with HIV immune pathogenesis markers. Although, we cannot rule out the possibility that some changes are partially a random consequence of the disease status, our data suggest that most likely reduced inflammation and immune recovery is a joint solution orchestrated by both the active fraction of the gut microbiota and the host.
authors.affiliation: Department of Infectious Diseases, University Hospital Ramón y Cajal and Ramón y Cajal Health Research Institute (IRYCIS), Madrid, Spain.
authors.forename: Sergio
authors.initials: S
authors.lastname: Serrano-Villar
authors.affiliation: Centro de Metabolómica y Bioanálisis (CEMBIO), Facultad de Farmacia, Universidad CEU San Pablo, Campus Montepríncipe, Madrid, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Rojo
authors.affiliation: Institute of Catalysis, Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain.
authors.forename: Mónica
authors.initials: M
authors.lastname: Martínez-Martínez
authors.affiliation: Institute of Animal Science, Universität Hohenheim, Stuttgart, Germany.
authors.forename: Simon
authors.initials: S
authors.lastname: Deusch
authors.affiliation: Foundation for the Promotion of Health and Biomedical Research in the Valencian Community (FISABIO) - Public Health, Valencia, Spain; Network Research Center for Epidemiology and Public Health (CIBER-ESP), Madrid, Spain.
authors.forename: Jorge F
authors.initials: JF
authors.lastname: Vázquez-Castellanos
authors.affiliation: Institute of Catalysis, Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Bargiela
authors.affiliation: Department of Pediatric Infectious Diseases, University Hospital La Paz, and La Paz Research Institute (IdiPAZ), Madrid, Spain.
authors.forename: Talía
authors.initials: T
authors.lastname: Sainz
authors.affiliation: Centro Sanitario Sandoval, Madrid, Spain.
authors.forename: Mar
authors.initials: M
authors.lastname: Vera
authors.affiliation: Department of Infectious Diseases, University Hospital Ramón y Cajal and Ramón y Cajal Health Research Institute (IRYCIS), Madrid, Spain.
authors.forename: Santiago
authors.initials: S
authors.lastname: Moreno
authors.affiliation: HIV Unit, Department of Internal Medicine, University Hospital Clínico San Carlos, Madrid, Spain.
authors.forename: Vicente
authors.initials: V
authors.lastname: Estrada
authors.affiliation: Foundation for the Promotion of Health and Biomedical Research in the Valencian Community (FISABIO) - Public Health, Valencia, Spain; Network Research Center for Epidemiology and Public Health (CIBER-ESP), Madrid, Spain.
authors.forename: María José
authors.initials: MJ
authors.lastname: Gosalbes
authors.affiliation: Foundation for the Promotion of Health and Biomedical Research in the Valencian Community (FISABIO) - Public Health, Valencia, Spain; Network Research Center for Epidemiology and Public Health (CIBER-ESP), Madrid, Spain; Instituto Cavanilles de Biodiversidad y Biología Evolutiva (Universidad de Valencia), Valencia, Spain.
authors.forename: Amparo
authors.initials: A
authors.lastname: Latorre
authors.affiliation: Institute of Animal Science, Universität Hohenheim, Stuttgart, Germany.
authors.forename: Jana
authors.initials: J
authors.lastname: Seifert
authors.affiliation: Centro de Metabolómica y Bioanálisis (CEMBIO), Facultad de Farmacia, Universidad CEU San Pablo, Campus Montepríncipe, Madrid, Spain. Electronic address: cbarbas@ceu.es.
authors.forename: Coral
authors.initials: C
authors.lastname: Barbas
authors.affiliation: Foundation for the Promotion of Health and Biomedical Research in the Valencian Community (FISABIO) - Public Health, Valencia, Spain; Network Research Center for Epidemiology and Public Health (CIBER-ESP), Madrid, Spain; Instituto Cavanilles de Biodiversidad y Biología Evolutiva (Universidad de Valencia), Valencia, Spain. Electronic address: andres.moya@uv.es.
authors.forename: Andrés
authors.initials: A
authors.lastname: Moya
authors.affiliation: Institute of Catalysis, Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain. Electronic address: mferrer@icp.csic.es.
authors.forename: Manuel
authors.initials: M
authors.lastname: Ferrer
mesh_terms: D023241:Antiretroviral Therapy, Highly Active; D001419:Bacteria / Q000378:metabolism*; D015415:Biomarkers; D018791:CD4 Lymphocyte Count; D016022:Case-Control Studies; D005260:Female; D000069196:Gastrointestinal Microbiome; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism* / Q000821:virology; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D007109:Immunity; D008297:Male; D055442:Metabolome; D055432:Metabolomics / Q000379:methods; D019562:Viral Load
chemical_list: D015415:Biomarkers
keywords: Antiretroviral therapy; Gut microbiota; HIV; Immune recovery; Metabolome; Metaproteome