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

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.

Effect of probiotics (Saccharomyces boulardii) on microbial translocation and inflammation in HIV-treated patients: a double-blind, randomized, placebo-controlled trial.

BACKGROUND: Microbial translocation has been associated with an increase in immune activation and inflammation in HIV infection despite effective highly active antiretroviral therapy. It has been shown that some probiotics have a beneficial effect by reducing intestinal permeability and, consequently, microbial translocation. OBJECTIVES: To assess changes in microbial translocation and inflammation after treatment with probiotics (Saccharomyces boulardii) in HIV-1-infected patients with virologic suppression. METHODS: A double-blind, randomized, placebo-controlled trial was conducted in 44 nonconsecutive HIV-1-infected patients with viral load of <20 copies per milliliter for at least 2 years. Patients were randomized to oral supplementation with probiotics or placebo during 12 weeks. Markers of microbial translocation (lipopolysaccharide-binding protein [LBP] and soluble CD14), inflammation (interleukin 6 [IL-6], tumor necrosis factor alpha, interferon gamma, high-sensitivity C-reactive protein), and immunological and clinical data were determined before and after the intervention and 3 months after treatment discontinuation. Quantitative variables were compared using the Mann-Whitney U test, and categorical variables were compared using the Fisher exact test. RESULTS: After 12 weeks of treatment, differences between the probiotic arm and the placebo arm were observed in LBP values (-0.30 vs +0.70 pg/mL) and IL-6 (-0.60 vs +0.78 pg/mL). These differences were also noted at 3 months after treatment withdrawal. Qualitative analysis was performed, defining a variable as "decreased" or "increased" from baseline LBP. A significant decrease of LBP at 12 weeks of treatment was observed (57.9% patients in the probiotic group vs 6.2% in the placebo group, P = 0.002). CONCLUSIONS: Treatment with S. boulardii decreases microbial translocation (LBP) and inflammation parameters (IL-6) in HIV-1-infected patients with long-term virologic suppression.

Prevalence and Factors Associated with Vitamin D Deficiency and Hyperparathyroidism in HIV-Infected Patients Treated in Barcelona.

Vitamin D deficiency is an important problem in patients with chronic conditions including those with human immunodeficiency virus (HIV) infection. The aim of this cross-sectional study was to identify the prevalence and factors associated with vitamin D deficiency and hyperparathyroidism in HIV patients attended in Barcelona. Cholecalciferol (25OH vitamin D3) and PTH levels were measured. Vitamin D insufficiency was defined as 25(OH) D < 20 ng/mL and deficiency as <12 ng/mL. Hyperparathyroidism was defined as PTH levels >65 pg/mL. Cases with chronic kidney failure, liver disease, treatments or conditions potentially affecting bone metabolism were excluded. Among the 566 patients included, 56.4% were exposed to tenofovir. Vitamin D insufficiency was found in 71.2% and 39.6% of those had deficiency. PTH was measured in 228 subjects, and 86 of them (37.7%) showed high levels. Adjusted predictors of vitamin D deficiency were nonwhite race and psychiatric comorbidity, while lipoatrophy was a protective factor. Independent risk factors of hyperparathyroidism were vitamin D < 12 ng/mL (OR: 2.14, CI 95%: 1.19-3.82, P: 0.01) and tenofovir exposure (OR: 3.55, CI 95%: 1.62-7.7, P: 0.002). High prevalence of vitamin deficiency and hyperparathyroidism was found in an area with high annual solar exposure.