Effect of Lactobacillus rhamnosus GG Supplementation on Intestinal Inflammation Assessed by PET/MRI Scans and Gut Microbiota Composition in HIV-Infected Individuals

From BugSigDB
Needs review
study design
prospective cohort
Citation
PMID
URI
Authors
Arnbjerg CJ, Vestad B, Hov JR, Pedersen KK, Jespersen S, Johannesen HH, Holm K, Halvorsen B, Fallentin E, Hansen AE, Lange T, Kjær A, Trøseid M, Fischer BM, Nielsen SD
Journal
Journal of acquired immune deficiency syndromes (1999)
Year
2018
BACKGROUND: Alterations in the gut microbiome have been associated with inflammation and increased cardiovascular risk in HIV-infected individuals. The aim of this study was to investigate the effects of the probiotic strain Lactobacillus rhamnosus GG (LGG) on intestinal inflammation, gut microbiota composition, and systemic markers of microbial translocation and inflammation in HIV-infected individuals. METHODS: This prospective, clinical interventional trial included 45 individuals [15 combination antiretroviral treatment (cART) naive and 30 cART treated] who ingested LGG twice daily at a dosage of 6 × 109 colony-forming units per capsule for a period of 8 weeks. Intestinal inflammation was assessed using F-2-fluoro-2-deoxy-D-glucose positron emission tomography/magnetic resonance imaging (F-FDG PET/MRI) scans in 15 individuals. Gut microbiota composition (V3-V4 region of the 16s rRNA gene) and markers of microbial translocation and inflammation (lipopolysaccharide, sCD14, sCD163, sCD25, high-sensitive CRP, IL-6, and tumor necrosis factor-alpha) were analyzed at baseline and after intervention. RESULTS: At baseline, evidence of intestinal inflammation was found in 75% of the participants, with no significant differences between cART-naive and cART-treated individuals. After LGG supplementation, a decrease in intestinal inflammation was detected on PET/MRI (-0.3 mean difference in the combined activity grade score from 6 regions, P = 0.006), along with a reduction of Enterobacteriaceae (P = 0.018) and Erysipelotrichaceae (P = 0.037) in the gut microbiome, with reduced Enterobacteriaceae among individuals with decreased F-FDG uptake on PET/MRI (P = 0.048). No changes were observed for soluble markers of microbial translocation and inflammation. CONCLUSIONS: A decrease in intestinal inflammation was found in HIV-infected individuals after ingestion of LGG along with a reduced abundance of Enterobacteriaceae, which may explain the local anti-inflammatory effect in the gut.

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
Denmark
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
combination antiretroviral therapy treated individuals after taking LGG probiotic for 8 weeks
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Persons with HIV
Group 0 sample size Number of subjects in the control (unexposed) group
27
Group 1 sample size Number of subjects in the case (exposed) group
27
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
16S variable region One or more hypervariable region(s) of the bacterial 16S gene
V3-V4
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


Alpha Diversity

Richness Number of species
unchanged

Signature 1

Needs review

Curated date: 2020-11-14

Curator: Michael Lutete

Revision editor(s): WikiWorks743

Source: Text, Supplementary Figure 3

Description: Effect of Probiotic LGG on Gut Microbiota Composition

Abundance in Group 1: increased abundance in combination antiretroviral therapy treated individuals after taking LGG probiotic for 8 weeks

NCBI Links
Ruminiclostridium
Lachnospiraceae

Revision editor(s): WikiWorks743

Signature 2

Needs review

Curated date: 2020-11-14

Curator: Michael Lutete

Revision editor(s): WikiWorks743

Source: Text, Supplementary Figure 3

Description: Effect of Probiotic LGG on Gut Microbiota Composition

Abundance in Group 1: decreased abundance in combination antiretroviral therapy treated individuals after taking LGG probiotic for 8 weeks

NCBI Links
Enterobacteriaceae
Erysipelotrichaceae

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
Denmark
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
combination antiretroviral therapy naive individuals after taking LGG probiotic for 8 weeks
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Persons with HIV
Group 0 sample size Number of subjects in the control (unexposed) group
13
Group 1 sample size Number of subjects in the case (exposed) group
13
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


Alpha Diversity

Richness Number of species
unchanged

Signature 1

Needs review

Curated date: 2020-11-14

Curator: Michael Lutete

Revision editor(s): WikiWorks743

Source: Text, Supplementary Figure 3

Description: Effect of Probiotic LGG on Gut Microbiota Composition

Abundance in Group 1: increased abundance in combination antiretroviral therapy naive individuals after taking LGG probiotic for 8 weeks

NCBI Links
Enterobacteriaceae
Erysipelotrichaceae

Revision editor(s): WikiWorks743

Signature 2

Needs review

Curated date: 2020-11-14

Curator: Michael Lutete

Revision editor(s): WikiWorks743

Source: Text, Supplementary Figure 3

Description: Effect of Probiotic LGG on Gut Microbiota Composition

Abundance in Group 1: decreased abundance in combination antiretroviral therapy naive individuals after taking LGG probiotic for 8 weeks

NCBI Links
Enterobacteriaceae
Erysipelotrichaceae

Revision editor(s): WikiWorks743

Experiment 3


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
Denmark
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
individuals with no change in uptake
Group 1 name Corresponds to the case (exposed) group for case-control studies
individuals with decreased F-2-fluoro-2-deoxy-D-glucose (F-FDG) uptake on positron emission tomography (PET)/magnetic resonance imaging (MRI)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Persons with HIV
Group 0 sample size Number of subjects in the control (unexposed) group
7
Group 1 sample size Number of subjects in the case (exposed) group
5
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


Alpha Diversity

Richness Number of species
unchanged

Signature 1

Needs review

Curated date: 2020-11-14

Curator: Michael Lutete

Revision editor(s): WikiWorks743

Source: Text, Figure 2

Description: Changes in relative abundance of Enterobacteriaceae after LGG supplementation in responders and nonresponders

Abundance in Group 1: decreased abundance in individuals with decreased F-2-fluoro-2-deoxy-D-glucose (F-FDG) uptake on positron emission tomography (PET)/magnetic resonance imaging (MRI)

NCBI Links
Enterobacteriaceae

Revision editor(s): WikiWorks743