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

From BugSigDB
Needs review
study design
randomized controlled trial
Citation
PMID
URI
Authors
Villar-García J, Güerri-Fernández R, Moya A, González A, Hernández JJ, Lerma E, Guelar A, Sorli L, Horcajada JP, Artacho A, D Auria G, Knobel H
Journal
PloS one
Year
2017
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.

Experiment 1


Needs review

Curated date: 2021/01/10

Curator: WikiWorks743

Revision editor(s): WikiWorks753, WikiWorks743

Subjects

Location of subjects Country from which study subjects were recruited
Spain
Host species Species from which microbiome was sampled (if applicable)
Homo sapiens
Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
Feces Cow dung,Cow pat,Droppings,Dung,Excrement,Excreta,Faeces,Fecal material,Fecal matter,Fewmet,Frass,Guano,Matières fécales@fr,Merde@fr,Ordure,Partie de la merde@fr,Piece of shit,Porción de mierda@es,Portion of dung,Portion of excrement,Portion of faeces,Portion of fecal material,Portion of fecal matter,Portion of feces,Portion of guano,Portion of scat,Portionem cacas,Scat,Spoor,Spraint,Stool,Teil der fäkalien@de,Feces
Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
HIV infection [X]Human immunodeficiency virus disease,[X]Human immunodeficiency virus disease (disorder),[X]Unspecified human immunodeficiency virus [HIV] disease,[X]Unspecified human immunodeficiency virus [HIV] disease (disorder),HIV - Human immunodeficiency virus infection,HIV INFECT,HIV Infection,HIV infection,HIV Infections,HIV infectious disease,HTLV III INFECT,HTLV III Infections,HTLV III LAV INFECT,HTLV III LAV Infections,HTLV WIII INFECTIONS,HTLV WIII LAV INFECTIONS,HTLV-III Infection,HTLV-III Infections,HTLV-III-LAV Infection,HTLV-III-LAV Infections,HUMAN IMMUNO VIRUS DIS,human immunodeficiency virus,Human immunodeficiency virus [HIV] disease,HUMAN IMMUNOdeficiency VIRUS [HIV] INFECTION,Human immunodeficiency virus caused disease or disorder,Human immunodeficiency virus disease,Human immunodeficiency virus disease (disorder),Human immunodeficiency virus disease or disorder,Human immunodeficiency virus infection,Human immunodeficiency virus infection (disorder),Human immunodeficiency virus infection, NOS,Human immunodeficiency virus infectious disease,human immunodeficiency virus infectious disease,Infection, HIV,Infection, HTLV-III,Infection, HTLV-III-LAV,Infections, HIV,Infections, HTLV-III,Infections, HTLV-III-LAV,LYMPHOTROPIC VIRUS TYPE III INFECTIONS HUMAN T,T LYMPHOTROPIC VIRUS TYPE III INFECT HUMAN,T Lymphotropic Virus Type III Infections, Human,T-Lymphotropic Virus Type III Infections, Human,Unspecified human immunodeficiency virus [HIV] disease (disorder)
Group 0 name Corresponds to the control (unexposed) group for case-control studies
baseline
Group 1 name Corresponds to the case (exposed) group for case-control studies
immunological non-responders assigned to treatment for 12 weeks
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
HIV-infected immunological non-responders (INR) who received S. boulardii probiotic
Group 0 sample size Number of subjects in the control (unexposed) group
11
Group 1 sample size Number of subjects in the case (exposed) group
11
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
2 months

Lab analysis

Sequencing type Experimental technique used for quantifying microbial abundance
16S
Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
Illumina

Statistical Analysis

Statistical test Statistical test or computational tool used for differential abundance testing
Mann-Whitney (Wilcoxon)
Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
0.05
MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
No



Signature 1

Needs review

Curated date: 2020-11-14

Curator: Michael Lutete

Revision editor(s): WikiWorks743

Source: Text, Figure S1

Description: Saccharomyces boulardii produces changes in some gut bacterial communities

Abundance in Group 1: increased abundance in immunological non-responders assigned to treatment for 12 weeks

NCBI Links
Megamonas
Desulfovibrio

Revision editor(s): WikiWorks743

Signature 2

Needs review

Curated date: 2020-11-14

Curator: Michael Lutete

Revision editor(s): WikiWorks743

Source: Text, Figure S1, Figure 3

Description: Saccharomyces boulardii produces changes in some gut bacterial communities

Abundance in Group 1: decreased abundance in immunological non-responders assigned to treatment for 12 weeks

NCBI Links
Clostridiaceae
Catenibacterium

Revision editor(s): WikiWorks743

Experiment 2


Needs review

Curated date: 2021/01/10

Curator: WikiWorks743

Revision editor(s): WikiWorks753, WikiWorks743

Subjects

Location of subjects Country from which study subjects were recruited
Spain
Host species Species from which microbiome was sampled (if applicable)
Homo sapiens
Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
Feces Cow dung,Cow pat,Droppings,Dung,Excrement,Excreta,Faeces,Fecal material,Fecal matter,Fewmet,Frass,Guano,Matières fécales@fr,Merde@fr,Ordure,Partie de la merde@fr,Piece of shit,Porción de mierda@es,Portion of dung,Portion of excrement,Portion of faeces,Portion of fecal material,Portion of fecal matter,Portion of feces,Portion of guano,Portion of scat,Portionem cacas,Scat,Spoor,Spraint,Stool,Teil der fäkalien@de,Feces
Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
HIV infection [X]Human immunodeficiency virus disease,[X]Human immunodeficiency virus disease (disorder),[X]Unspecified human immunodeficiency virus [HIV] disease,[X]Unspecified human immunodeficiency virus [HIV] disease (disorder),HIV - Human immunodeficiency virus infection,HIV INFECT,HIV Infection,HIV infection,HIV Infections,HIV infectious disease,HTLV III INFECT,HTLV III Infections,HTLV III LAV INFECT,HTLV III LAV Infections,HTLV WIII INFECTIONS,HTLV WIII LAV INFECTIONS,HTLV-III Infection,HTLV-III Infections,HTLV-III-LAV Infection,HTLV-III-LAV Infections,HUMAN IMMUNO VIRUS DIS,human immunodeficiency virus,Human immunodeficiency virus [HIV] disease,HUMAN IMMUNOdeficiency VIRUS [HIV] INFECTION,Human immunodeficiency virus caused disease or disorder,Human immunodeficiency virus disease,Human immunodeficiency virus disease (disorder),Human immunodeficiency virus disease or disorder,Human immunodeficiency virus infection,Human immunodeficiency virus infection (disorder),Human immunodeficiency virus infection, NOS,Human immunodeficiency virus infectious disease,human immunodeficiency virus infectious disease,Infection, HIV,Infection, HTLV-III,Infection, HTLV-III-LAV,Infections, HIV,Infections, HTLV-III,Infections, HTLV-III-LAV,LYMPHOTROPIC VIRUS TYPE III INFECTIONS HUMAN T,T LYMPHOTROPIC VIRUS TYPE III INFECT HUMAN,T Lymphotropic Virus Type III Infections, Human,T-Lymphotropic Virus Type III Infections, Human,Unspecified human immunodeficiency virus [HIV] disease (disorder)
Group 0 name Corresponds to the control (unexposed) group for case-control studies
baseline
Group 1 name Corresponds to the case (exposed) group for case-control studies
immunological responders assigned to treatment for 12 weeks
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
HIV-infected immunological responders (IR) who received S. boulardii probiotic
Group 0 sample size Number of subjects in the control (unexposed) group
11
Group 1 sample size Number of subjects in the case (exposed) group
11
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
2 months

Lab analysis

Sequencing type Experimental technique used for quantifying microbial abundance
16S
Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
Illumina

Statistical Analysis

Statistical test Statistical test or computational tool used for differential abundance testing
Mann-Whitney (Wilcoxon)
Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
0.05
MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
No



Signature 1

Needs review

Curated date: 2020-11-14

Curator: Michael Lutete

Revision editor(s): WikiWorks743

Source: Text, Figure S1

Description: Saccharomyces boulardii produces changes in some gut bacterial communities

Abundance in Group 1: increased abundance in immunological responders assigned to treatment for 12 weeks

NCBI Links
Megamonas
Desulfovibrio

Revision editor(s): WikiWorks743

Signature 2

Needs review

Curated date: 2020-11-14

Curator: Michael Lutete

Revision editor(s): WikiWorks743

Source: Text, Figure S1, Figure 3

Description: Saccharomyces boulardii produces changes in some gut bacterial communities

Abundance in Group 1: decreased abundance in immunological responders assigned to treatment for 12 weeks

NCBI Links
Clostridiaceae
Catenibacterium

Revision editor(s): WikiWorks743