title: Impact of probiotic Saccharomyces boulardii on the gut microbiome composition in HIV-treated patients: A double-blind, randomised, placebo-controlled trial.
abstract: Dysbalance in gut microbiota has been linked to increased microbial translocation, leading to chronic inflammation in HIV-patients, even under effective HAART. Moreover, microbial translocation is associated with insufficient reconstitution of CD4+T cells, and contributes to the pathogenesis of immunologic non-response. In a double-blind, randomised, placebo-controlled trial, we recently showed that, compared to placebo, 12 weeks treatment with probiotic Saccharomyces boulardii significantly reduced plasma levels of bacterial translocation (Lipopolysaccharide-binding protein or LBP) and systemic inflammation (IL-6) in 44 HIV virologically suppressed patients, half of whom (n = 22) had immunologic non-response to antiretroviral therapy (<270 CD4+Tcells/μL despite long-term suppressed viral load). The aim of the present study was to investigate if this beneficial effect of the probiotic Saccharomyces boulardii is due to modified gut microbiome composition, with a decrease of some species associated with higher systemic levels of microbial translocation and inflammation. In this study, we used 16S rDNA gene amplification and parallel sequencing to analyze the probiotic impact on the composition of the gut microbiome (faecal samples) in these 44 patients randomized to receive oral supplementation with probiotic or placebo for 12 weeks. Compared to the placebo group, in individuals treated with probiotic we observed lower concentrations of some gut species, such as those of the Clostridiaceae family, which were correlated with systemic levels of bacterial translocation and inflammation markers. In a sub-study of these patients, we observed significantly higher parameters of microbial translocation (LBP, soluble CD14) and systemic inflammation in immunologic non-responders than in immunologic responders, which was correlated with a relative abundance of specific gut bacterial groups (Lachnospiraceae genus and Proteobacteria). Thus, in this work, we propose a new therapeutic strategy using the probiotic yeast S. boulardii to modify gut microbiome composition. Identifying pro-inflammatory species in the gut microbiome could also be a useful new marker of poor immune response and a new therapeutic target.
authors.affiliation: Department of Infectious Diseases, Hospital del Mar, Barcelona, Spain.|IMIM (Hospital del Mar Medical Research Institute, Institut Hospital del Mar d'Investigacions Mediques), Barcelona, Spain.|Department of Medicine, Universitat Autònoma de Barcelona, Spain.
authors.forename: Judit
authors.identifier: http://orcid.org/0000-0003-2813-8426
authors.initials: J
authors.lastname: Villar-García
authors.affiliation: Department of Infectious Diseases, Hospital del Mar, Barcelona, Spain.|IMIM (Hospital del Mar Medical Research Institute, Institut Hospital del Mar d'Investigacions Mediques), Barcelona, Spain.|Department of Medicine, Universitat Autònoma de Barcelona, Spain.
authors.forename: Robert
authors.initials: R
authors.lastname: Güerri-Fernández
authors.affiliation: Joint Unit of Research in Genomics and Health, Foundation for the Promotion of Health and Biomedical Research in the Valencian Community (FISABIO) and Cavanilles Institute of Biodiversity and Evolutionary Biology (Universitat de València), València, Spain.|CIBER en Epidemiología y Salud Pública, Madrid, Spain.
authors.forename: Andrés
authors.initials: A
authors.lastname: Moya
authors.affiliation: Department of Infectious Diseases, Hospital del Mar, Barcelona, Spain.|IMIM (Hospital del Mar Medical Research Institute, Institut Hospital del Mar d'Investigacions Mediques), Barcelona, Spain.
authors.forename: Alicia
authors.initials: A
authors.lastname: González
authors.affiliation: Reference Laboratory of Catalonia, Barcelona, Spain.
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Hernández
authors.affiliation: Department of Infectious Diseases, Hospital del Mar, Barcelona, Spain.|IMIM (Hospital del Mar Medical Research Institute, Institut Hospital del Mar d'Investigacions Mediques), Barcelona, Spain.
authors.forename: Elisabet
authors.initials: E
authors.lastname: Lerma
authors.affiliation: Department of Infectious Diseases, Hospital del Mar, Barcelona, Spain.|IMIM (Hospital del Mar Medical Research Institute, Institut Hospital del Mar d'Investigacions Mediques), Barcelona, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Guelar
authors.affiliation: Department of Infectious Diseases, Hospital del Mar, Barcelona, Spain.|IMIM (Hospital del Mar Medical Research Institute, Institut Hospital del Mar d'Investigacions Mediques), Barcelona, Spain.
authors.forename: Luisa
authors.initials: L
authors.lastname: Sorli
authors.affiliation: Department of Infectious Diseases, Hospital del Mar, Barcelona, Spain.|IMIM (Hospital del Mar Medical Research Institute, Institut Hospital del Mar d'Investigacions Mediques), Barcelona, Spain.|Department of Medicine, Universitat Autònoma de Barcelona, Spain.
authors.forename: Juan P
authors.initials: JP
authors.lastname: Horcajada
authors.affiliation: Joint Unit of Research in Genomics and Health, Foundation for the Promotion of Health and Biomedical Research in the Valencian Community (FISABIO) and Cavanilles Institute of Biodiversity and Evolutionary Biology (Universitat de València), València, Spain.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Artacho
authors.affiliation: Joint Unit of Research in Genomics and Health, Foundation for the Promotion of Health and Biomedical Research in the Valencian Community (FISABIO) and Cavanilles Institute of Biodiversity and Evolutionary Biology (Universitat de València), València, Spain.|CIBER en Epidemiología y Salud Pública, Madrid, Spain.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: D Auria
authors.affiliation: Department of Infectious Diseases, Hospital del Mar, Barcelona, Spain.|IMIM (Hospital del Mar Medical Research Institute, Institut Hospital del Mar d'Investigacions Mediques), Barcelona, Spain.|Department of Medicine, Universitat Autònoma de Barcelona, Spain.
authors.forename: Hernando
authors.initials: H
authors.lastname: Knobel
mesh_terms: D000328:Adult; D004311:Double-Blind Method; D005260:Female; D015658:HIV Infections / Q000382:microbiology*; D006801:Humans; D007422:Intestines / Q000382:microbiology*; D008297:Male; D064307:Microbiota; D008875:Middle Aged; D010919:Placebos; D019936:Probiotics; D000069983:Saccharomyces boulardii
chemical_list: D010919:Placebos