title: The effects of prebiotics on microbial dysbiosis, butyrate production and immunity in HIV-infected subjects.
abstract: Altered interactions between the gut mucosa and bacteria during HIV infection seem to contribute to chronic immune dysfunction. A deeper understanding of how nutritional interventions could ameliorate gut dysbiosis is needed. Forty-four subjects, including 12 HIV+viremic untreated (VU) patients, 23 antiretroviral therapy-treated (ART+) virally suppressed patients (15 immunological responders and 8 non-responders) and 9 HIV-controls (HIV-), were blindly randomized to receive either prebiotics (scGOS/lcFOS/glutamine) or placebo (34/10) over 6 weeks in this pilot study. We assessed fecal microbiota composition using deep 16S rRNA gene sequencing and several immunological and genetic markers involved in HIV immunopathogenesis. The short dietary supplementation attenuated HIV-associated dysbiosis, which was most apparent in VU individuals but less so in ART+subjects, whose gut microbiota was found more resilient. This compositional shift was not observed in the placebo arm. Significantly, declines in indirect markers of bacterial translocation and T-cell activation, improvement of thymic output, and changes in butyrate production were observed. Increases in the abundance of Faecalibacterium and Lachnospira strongly correlated with moderate but significant increases of butyrate production and amelioration of the inflammatory biomarkers soluble CD14 and high-sensitivity C-reactive protein, especially among VU. Hence, the bacterial butyrate synthesis pathway holds promise as a viable target for interventions.
authors.affiliation: Department of Infectious Diseases, Hospital Universitario Ramón y Cajal, Facultad de Medicina, Universidad de Alcalá (IRYCIS), Madrid, Spain.
authors.forename: S
authors.initials: S
authors.lastname: Serrano-Villar
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 Biodiversidad y Biología Evolutiva (Universidad de Valencia), Valencia, Spain.|CIBER en Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.
authors.forename: J F
authors.initials: JF
authors.lastname: Vázquez-Castellanos
authors.affiliation: Department of Infectious Diseases, Hospital Universitario Ramón y Cajal, Facultad de Medicina, Universidad de Alcalá (IRYCIS), Madrid, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Vallejo
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 Biodiversidad y Biología Evolutiva (Universidad de Valencia), Valencia, Spain.|CIBER en Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Latorre
authors.affiliation: Department of Pediatric Infectious Diseases, University Hospital La Paz, and La Paz Research Institute, Madrid, Spain.
authors.forename: T
authors.initials: T
authors.lastname: Sainz
authors.affiliation: Laboratory of Immunovirology, Biomedicine Institute of Seville (IBIS), Department of Infectious Diseases, University Hospital Virgen del Rocío, Sevilla, Spain.
authors.forename: S
authors.initials: S
authors.lastname: Ferrando-Martínez
authors.affiliation: Centro de Metabolómica y Bioanálisis (CEMBIO), Facultad de Farmacia, CEU San Pablo University, Madrid, Spain.
authors.forename: D
authors.initials: D
authors.lastname: Rojo
authors.affiliation: Department of Biochemistry, University Hospital Ramón y Cajal-IRYCIS, Madrid, Spain.|CIBER of Obesity and Nutrition Pathophysiology (CIBEROBN), Madrid, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Martínez-Botas
authors.affiliation: Centro Sandoval, Madrid, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Del Romero
authors.affiliation: Department of Infectious Diseases, Hospital Universitario Ramón y Cajal, Facultad de Medicina, Universidad de Alcalá (IRYCIS), Madrid, Spain.
authors.forename: N
authors.initials: N
authors.lastname: Madrid
authors.affiliation: Laboratory of Immunovirology, Biomedicine Institute of Seville (IBIS), Department of Infectious Diseases, University Hospital Virgen del Rocío, Sevilla, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Leal
authors.affiliation: Food Technology Department, Agrotecnio Center, University of Lleida, Spain.
authors.forename: J I
authors.initials: JI
authors.lastname: Mosele
authors.affiliation: Food Technology Department, Agrotecnio Center, University of Lleida, Spain.
authors.forename: M J
authors.initials: MJ
authors.lastname: Motilva
authors.affiliation: Centro de Metabolómica y Bioanálisis (CEMBIO), Facultad de Farmacia, CEU San Pablo University, Madrid, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Barbas
authors.affiliation: Institute of Catalysis, Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Ferrer
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 Biodiversidad y Biología Evolutiva (Universidad de Valencia), Valencia, Spain.|CIBER en Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Moya
authors.affiliation: Department of Infectious Diseases, Hospital Universitario Ramón y Cajal, Facultad de Medicina, Universidad de Alcalá (IRYCIS), Madrid, Spain.
authors.forename: S
authors.initials: S
authors.lastname: Moreno
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 Biodiversidad y Biología Evolutiva (Universidad de Valencia), Valencia, Spain.|CIBER en Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.
authors.forename: M J
authors.initials: MJ
authors.lastname: Gosalbes
authors.affiliation: HIV Unit, Department of Internal Medicine, University Hospital Clínico San Carlos, Madrid, Spain.
authors.forename: V
authors.initials: V
authors.lastname: Estrada
mesh_terms: D000328:Adult; D001419:Bacteria / Q000235:genetics*; D002087:Butyrates / Q000378:metabolism; D019587:Dietary Supplements; D064806:Dysbiosis / Q000209:etiology / Q000382:microbiology / Q000517:prevention & control*; D005243:Feces / Q000382:microbiology; D005260:Female; D000069196:Gastrointestinal Microbiome / Q000235:genetics* / Q000276:immunology; D015658:HIV Infections / Q000150:complications / Q000276:immunology / Q000382:microbiology*; D015497:HIV-1 / Q000276:immunology*; D054884:Host-Pathogen Interactions; D006801:Humans; D007109:Immunity; D007413:Intestinal Mucosa / Q000276:immunology* / Q000382:microbiology / Q000821:virology; D008297:Male; D008875:Middle Aged; D015990:Placebo Effect; D056692:Prebiotics / Q000008:administration & dosage*; D012336:RNA, Ribosomal, 16S / Q000032:analysis*
chemical_list: D002087:Butyrates; D056692:Prebiotics; D012336:RNA, Ribosomal, 16S