Reduced Levels of D-dimer and Changes in Gut Microbiota Composition After Probiotic Intervention in HIV-Infected Individuals on Stable ART

Study information

Reviewed Marked as Reviewed by ChiomaBlessing on 2024-2-5

study design

randomized controlled trial

Citation

PMID PubMed identifier for scientific articles.

26258571

DOI Digital object identifier for electronic documents.

10.1097/QAI.0000000000000784

URI

Authors

Stiksrud B, Nowak P, Nwosu FC, Kvale D, Thalme A, Sonnerborg A, Ueland PM, Holm K, Birkeland SE, Dahm AE, Sandset PM, Rudi K, Hov JR, Dyrhol-Riise AM, Trøseid M

Journal

Journal of acquired immune deficiency syndromes (1999)

Year

2015

BACKGROUND: Microbial translocation and chronic inflammation may contribute to non-AIDS morbidity in patients with HIV. This study assessed the impact of probiotic intervention on microbial translocation and inflammation in patients on antiretroviral therapy with viral suppression and subnormal CD4 count. METHODS: Thirty-two patients receiving antiretroviral therapy (CD4 <500 cells/μL) were randomized in a double-blind fashion to multistrain daily probiotics (n = 15), placebo (n = 9), or controls (n = 8) for 8 weeks. Soluble inflammation markers, D-dimer, lipopolysaccharide (LPS), sCD14, T-cell activation, tryptophan metabolites, and gut microbiota composition were analyzed at baseline and end of study. Nonparametric statistics were applied. RESULTS: Twenty-four participants completed the study and were included in as-treated analyses. In patients receiving probiotics, there was a significant reduction in D-dimer levels (median change 33%, P = 0.03) and a tendency to reduced levels of C-reactive protein (CRP) (P = 0.05) and interleukin (IL)-6 (P = 0.06). The changes in CRP and IL-6 were highly correlated (r = 0.95, P < 0.01), whereas changes in D-dimer did not correlate with changes in CRP or IL-6. Increases in Bifidobacteria (P = 0.04) and Lactobacilli (P = 0.06) were observed in the probiotic group, whereas the relative abundance of Bacteroides decreased (P ≤ 0.01). No significant changes were seen in markers of microbial translocation or T-cell activation. However, the expansion of Bifidobacteria correlated negatively with differences in LPS (r = -0.77, P = 0.01), whereas the reduction in Bacteroides correlated positively with changes in LPS during the study period (r = 0.72, P = 0.02). CONCLUSIONS: Probiotic intervention seemed to reduce markers of coagulation and inflammation without overt changes in microbial translocation. These findings warrant further studies in larger cohorts with long-term follow-up.

Experiment 1

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Curated date: 2021/01/10

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Subjects

Location of subjects: Norway; Sweden

Host species Species from which microbiome was sampled. Contact us to have more species added.: 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,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),hIV infection

Group 0 name Corresponds to the control (unexposed) group for case-control studies: baseline probiotic group

Group 1 name Corresponds to the case (exposed) group for case-control studies: Probiotic group after 8 weeks of intervention

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: HIV-infected on antiretroviral therapy allocated to probiotic group after 8 weeks of intervention

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: 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

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).: relative abundances

Statistical test: 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

Shannon Estimator of species richness and species evenness: more weight on species richness: unchanged

Richness Number of species: unchanged

Signature 1

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Source: Figure 3 & Supplementary figure S4A

Description: Gut microbiota composition after probiotic intervention at 8 weeks compared to baseline group (in HIV-infected individuals on stable antiretroviral therapy (ART))

Abundance in Group 1: increased abundance in Probiotic group after 8 weeks of intervention

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Actinomycetes
Bacillota
Bifidobacterium
Oscillospiraceae

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Signature 2

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Source: Figure 3 & Supplementary figure S4A

Description: Gut microbiota composition after probiotic intervention at 8 weeks compared to baseline group (in HIV-infected individuals on stable antiretroviral therapy (ART))

Abundance in Group 1: decreased abundance in Probiotic group after 8 weeks of intervention

NCBI	Quality Control	Links
Bacteroides
Bacteroidota

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Experiment 2

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Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies: Non-probiotic intervention group (after 8 weeks)

Group 1 name Corresponds to the case (exposed) group for case-control studies: Probiotic intervention group (after 8 weeks)

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: Probiotic intervention group (after 8 weeks)

Group 0 sample size Number of subjects in the control (unexposed) group: 13

Lab analysis

Statistical Analysis

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness: unchanged

Richness Number of species: unchanged

Signature 1

Edit History Delete

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Reviewed Marked as Reviewed by ChiomaBlessing on 2024-2-5

Curated date: 2021/01/10

Curator: Michael Lutete

Revision editor(s): WikiWorks, ChiomaBlessing

Source: Figure 3

Description: Gut microbiota composition after probiotic intervention at 8 weeks compared to non-probiotic group (in HIV-infected individuals on stable antiretroviral therapy (ART))

Abundance in Group 1: increased abundance in Probiotic intervention group (after 8 weeks)

NCBI	Quality Control	Links
Lactobacillus

Revision editor(s): WikiWorks, ChiomaBlessing