Targeting the Gut Microbiota of Vertically HIV-Infected Children to Decrease Inflammation and Immunoactivation: A Pilot Clinical Trial
Talía Sainz,
Laura Diaz,
David Rojo,
María Isabel Clemente,
Coral Barbas,
María José Gosalbes,
Nuria Jimenez-Hernandez,
Luis Escosa,
Sara Guillen,
José Tomás Ramos,
María Ángeles Muñoz-Fernández,
María Luisa Navarro,
María José Mellado,
Sergio Serrano-Villar
Affiliations
Talía Sainz
Servicio de Pediatría, Hospital Universitario La Paz and IdiPAZ, 28046 Madrid, Spain
Laura Diaz
Plataforma de Citometría (Laura Diaz), Instituto de Investigación Sanitaria Gregorio Marañón (IsSGM), Hospital Universitario Gregorio Marañon, 28009 Madrid, Spain
David Rojo
Centre for Metabolomics and Bioanalysis (CEMBIO), Department of Chemistry and Biochemistry, Facultad de Farmacia, Universidad San Pablo-CEUUniversities, Boadilla Monte, 28668 Madrid, Spain
María Isabel Clemente
Plataforma de Citometría (Laura Diaz), Instituto de Investigación Sanitaria Gregorio Marañón (IsSGM), Hospital Universitario Gregorio Marañon, 28009 Madrid, Spain
Coral Barbas
Centre for Metabolomics and Bioanalysis (CEMBIO), Department of Chemistry and Biochemistry, Facultad de Farmacia, Universidad San Pablo-CEUUniversities, Boadilla Monte, 28668 Madrid, Spain
María José Gosalbes
Área Genómica y Salud, Fundación para el Fomento de la Investigación Sanitaria y Biomédica (FISABIO), 46020 Valencia, Spain
Nuria Jimenez-Hernandez
Área Genómica y Salud, Fundación para el Fomento de la Investigación Sanitaria y Biomédica (FISABIO), 46020 Valencia, Spain
Luis Escosa
Servicio de Pediatría, Hospital Universitario La Paz and IdiPAZ, 28046 Madrid, Spain
Sara Guillen
Red de Investigación CoRISpe Integrada en la Red en Infectología Pediátrica (RITIP), 28046 Madrid, Spain
José Tomás Ramos
Red de Investigación CoRISpe Integrada en la Red en Infectología Pediátrica (RITIP), 28046 Madrid, Spain
María Ángeles Muñoz-Fernández
Red de Investigación CoRISpe Integrada en la Red en Infectología Pediátrica (RITIP), 28046 Madrid, Spain
María Luisa Navarro
Red de Investigación CoRISpe Integrada en la Red en Infectología Pediátrica (RITIP), 28046 Madrid, Spain
María José Mellado
Servicio de Pediatría, Hospital Universitario La Paz and IdiPAZ, 28046 Madrid, Spain
Sergio Serrano-Villar
Área de Enfermedades Infecciosas del Centro de Investigación Biomédica en Red del Instituto de Salud Carlos III (CIBERINFEC), Instituto de Salud Carlos III, 28029 Madrid, Spain
Aims: Children with HIV exhibit chronic inflammation and immune dysfunction despite antiretroviral therapy (ART). Strategies targeting persistent inflammation are needed to improve health in people living with HIV. The gut microbiota likely interacts with the immune system, but the clinical implications of modulating the dysbiosis by nutritional supplementation are unclear. Methods: Pilot, double-blind, randomized placebo-controlled trial in which 24 HIV-infected on ART were randomized to supplementation with a daily mixture of symbiotics, omega-3/6 fatty acids and amino acids, or placebo four weeks, in combination with ART. We analyzed inflammatory markers and T-cell activation changes and their correlations with shifts in fecal microbiota. Results: Twenty-four HIV-infected children were recruited and randomized to receive a symbiotic nutritional supplement or placebo. Mean age was 12 ± 3.9 years, 62.5% were female. All were on ART and had HIV RNA < 50/mL. We did not detect changes in inflammatory (IL-6, IL-7, IP-10), microbial translocation (sCD14), mucosal integrity markers (IFABP, zonulin) or the kynurenine to tryptophan ratio, or changes in markers of the adaptive immune response in relation to the intervention. However, we found correlations between several key bacteria and the assessed inflammatory and immunological parameters, supporting a role of the microbiota in immune modulation in children with HIV. Conclusions: In this exploratory study, a four-week nutritional supplementation had no significant effects in terms of decreasing inflammation, microbial translocation, or T-cell activation in HIV-infected children. However, the correlations found support the interaction between gut microbiota and the immune system.