Previous research has shown that the severity of immunodeficiency in human immunodeficiency virus (HIV) infection is related to changes in both the gut virome and bacterial microbiome. Although microbiota-targeted interventions are considered nowadays a potential therapeutic strategy for HIV-infected subjects, little data is available regarding the efficacy of those interventions in humans.
A new double-blind, randomised, placebo-controlled trial, led by Dr. Hernando Knobel from the Hospital del Mar and Universitat Autònoma de Barcelona (Spain), has found that changes in gut microbiome composition following treatment with a probiotic are related to microbial translocation and inflammation in HIV-infected patients undergoing standard treatments.
The researchers investigated whether the beneficial effects previously reported for the probiotic Saccharomyces boulardii on plasma levels of bacterial translocation markers and inflammation markers were due to modified gut microbiome composition.
44 chronically HIV-infected patients with undetectable plasma viral load (<20 copies/mL) for at least 2 years and a stable highly active antiretroviral therapy (HAART) regimen (22 immunological responders ->400 CD4+T cells/mL- and 22 immunodiscordant or immunological non-responders -defined as individuals with an persistent unfavourable immunologic response of <270 CD4+T cells/mL despite long-term suppressed viral load) were randomised to receive either oral supplementation with the probiotic S. boulardii (capsules with 56.5 mg living yeasts, 2 capsules 3 times per day) or placebo for 12 weeks. Their faecal samples were analysed through 16S rDNA gene amplification and parallel sequencing. Serum levels of microbial translocation markers (lipopolysaccharide-binding protein or LBP and soluble CD14 or sCD14) and inflammation markers (interleukin (IL)-6, high sensitivity C-reactive protein or hs-CRP, Erythrocyte Sedimentation Rate or ESR and b2 microglobulin) were also measured.
At baseline, microbial translocation assessed by serum LBP was independently correlated with markers of systemic inflammation including hs-CRP, ESR and soluble CD14.
Probiotic treatment for 12 weeks led to a significant decrease in some Clostridiales, such as Clostridiaceae and Catenibacterium communities, and an increase in levels of Megamonas and Desulfovibrionales (Proteobacteria) from baseline, compared with placebo. These effects on gut microbiota composition were similar in the groups of immunological non-responders and immunological responders.
Besides this, in the immunological non-responder group the proportion (relative abundance) of bacteria in the Clostridia genera was correlated with plasma concentrations of soluble CD14, LBP, and IL-6 at baseline (before the intervention). However, in the probiotic treated group these correlations were not statistically significant, which researchers attribute to a decrease in these bacterial communities from the probiotic effect.
Finally, at baseline immunological non-responders had higher microbial translocation -high LBP was related to being an immunological non-responder and it was the only marker assessed that could explain immunological non-response-and a higher proportion of some pro-inflammatory species such as Firmicutes species (Clostridia), Proteobacteria and Lachnospiraceae.
In conclusion, S. boulardii can influence gut microbiome composition -specifically by decreasing pro-inflammatory species- in treated HIV-infected patients and this effect could be related to modulating parameters of microbial translocation and systemic inflammation.
Villar-García J, Güerri-Fernández R, Moya A, et al. Impact of probiotic Saccharomyces boulardii on the gut microbiome composition in HIV-treated patients: A double-blind, randomised, placebo-controlled trial. PLoS One. 2017; 12(4):e0173802. doi: 10.1371/journal.pone.0173802.
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