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Randomized Controlled Trial
. 2017 Apr 7;12(4):e0173802.
doi: 10.1371/journal.pone.0173802. eCollection 2017.

Impact of probiotic Saccharomyces boulardii on the gut microbiome composition in HIV-treated patients: A double-blind, randomised, placebo-controlled trial

Judit Villar-García  1   2   3 , Robert Güerri-Fernández  1   2   3 , Andrés Moya  4   5 , Alicia González  1   2 , Juan J Hernández  6 , Elisabet Lerma  1   2 , Ana Guelar  1   2 , Luisa Sorli  1   2 , Juan P Horcajada  1   2   3 , Alejandro Artacho  4 , Giuseppe D Auria  4   5 , Hernando Knobel  1   2   3
Affiliations
Randomized Controlled Trial

Impact of probiotic Saccharomyces boulardii on the gut microbiome composition in HIV-treated patients: A double-blind, randomised, placebo-controlled trial

Judit Villar-García et al. PLoS One. .

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.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. CONSORT flow diagram.
Fig 2
Fig 2. Canonical correspondence analysis.
Fig 3
Fig 3. Changes in the proportion of Clostridiales after the interventions.
Fig 4
Fig 4. Correlations between relative abundance of Clostridiales and soluble CD14 (4A), LBP (4B) and IL6 (4C) before the intervention (INR).
LBP, Lipopolisaccharide Binding-Proteine; IL6, interleukin-6.
Fig 5
Fig 5. Correlations between relative abundance of Clostridiales and soluble CD14 (5A), LBP (5B) and IL6 (5C) after probiotic treatment.
LBP, Lipopolisaccharide Binding-Proteine; IL6, interleukin-6.
See this image and copyright information in PMC

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