Immune activation and inflammation in lactating women on combination antiretroviral therapy: role of gut dysfunction and gut microbiota imbalance
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Study information
-
Quality control
- Retracted paper
- Contamination issues suspected
- Batch effect issues suspected
- Uncontrolled confounding suspected
- Results are suspect (various reasons)
- Tags applied
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
Munjoma PT, Chandiwana P, Wyss J, Mazhandu AJ, Jordi SBU, Gutsire R, Katsidzira L, Yilmaz B, Misselwitz B, Duri K
Journal
Frontiers in immunology
Year
2023
Keywords:
HIV, fecal calprotectin, gut microbiota, lactating women, microbial translocation, resource limited setting, systemic inflammation
INTRODUCTION: Combination antiretroviral therapy (cART) effectively controls HIV; however, chronic low-level viremia and gut microbiota dysbiosis remain significant drivers of gut and systemic inflammation. In this study, we explored the relationship between gut microbiota composition, intestinal inflammation, microbial translocation, and systemic inflammation in women on cART in Sub-Saharan Africa. METHODS: We conducted a study in HIV-infected and HIV-uninfected lactating women followed up at 6 weeks and 6 months postpartum in Harare, Zimbabwe. We used 16S ribosomal Ribonucleic Acid (rRNA) sequencing and MesoScale Discovery V-Plex assays to examine the gut microbiome and to quantify plasma inflammatory biomarkers, respectively. In addition, we measured fecal calprotectin, plasma lipopolysaccharide-binding protein (LBP), and soluble cluster of differentiation 14 (sCD14) by enzyme-linked immunosorbent assay to assess gut inflammation, microbial translocation, and monocyte/macrophage activation. RESULTS: A group of 77 lactating women were studied, of which 35% were HIV-infected. Fecal calprotectin levels were similar by HIV status at both follow-up time points. In the HIV-infected group at 6 weeks postpartum, fecal calprotectin was elevated: median (interquartile range) [158.1 µg/g (75.3-230.2)] in women who had CD4+ T-lymphocyte counts <350 cells/µL compared with those with ≥350 cells/µL [21.1 µg/g (0-58.4)], p = 0.032. Plasma sCD14 levels were significantly higher in the HIV-infected group at both 6 weeks and 6 months postpartum, p < 0.001. Plasma LBP levels were similar, but higher levels were observed in HIV-infected women with elevated fecal calprotectin. We found significant correlations between fecal calprotectin, LBP, and sCD14 with proinflammatory cytokines. Gut microbial alpha diversity was not affected by HIV status and was not affected by use of antibiotic prophylaxis. HIV significantly affected microbial beta diversity, and significant differences in microbial composition were noted. The genera Slackia and Collinsella were relatively more abundant in the HIV-infected group, whereas a lower relative abundance of Clostriduim sensu_stricto_1 was observed. Our study also found correlations between gut microbial taxa abundance and systemic inflammatory biomarkers. DISCUSSION AND CONCLUSION: HIV-infected lactating women had increased immune activation and increased microbial translocation associated with increased gut inflammation. We identified correlations between the gut inflammation and microbial composition, microbial translocation, and systemic inflammation. The interplay of these parameters might affect the health of this vulnerable population.
Experiment 1
Needs review
Curated date: 2024/10/02
Curator: Paavni Goyal
Revision editor(s): Paavni Goyal, KateRasheed, Aleru Divine
Subjects
- Location of subjects
- Zimbabwe
- 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
- HIV - uninfected
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- HIV - infected
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- The HIV-infected group consists of HIV-infected lactating women who were followed up at 6 weeks postpartum.
- Group 0 sample size Number of subjects in the control (unexposed) group
- 48
- Group 1 sample size Number of subjects in the case (exposed) group
- 25
Lab analysis
- Sequencing type
- 16S
- 16S variable region One or more hypervariable region(s) of the bacterial 16S gene
- V5-V6
- Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
- Ion Torrent
Statistical Analysis
- Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
- relative abundances
- Statistical test
- MaAsLin2
- 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)?
- Yes
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
- Simpson Estimator of species richness and species evenness: more weight on species evenness
- unchanged
Signature 1
Needs review
Source: Figure 6A
Description: Certain bacterial taxa were found to have increased abundance in HIV-infected women.
Abundance in Group 1: increased abundance in HIV - infected
| NCBI | Quality Control | Links |
|---|---|---|
| Collinsella | ||
| Coriobacteriales | ||
| Micrococcaceae | ||
| Slackia |
Revision editor(s): Paavni Goyal, KateRasheed
Signature 2
Needs review
Source: Figure 6A, Table 3
Description: Significant decrease in the HIV-infected group at 6weeks postpartum.
Abundance in Group 1: decreased abundance in HIV - infected
| NCBI | Quality Control | Links |
|---|---|---|
| Clostridium | ||
| Clostridiaceae |
Revision editor(s): Paavni Goyal, KateRasheed
Experiment 2
Needs review
Differences from previous experiment shown
Subjects
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- The HIV-infected group consists of HIV-infected lactating women who were followed up at 6 months postpartum.
- Group 0 sample size Number of subjects in the control (unexposed) group
- 42
- Group 1 sample size Number of subjects in the case (exposed) group
- 23
Lab analysis
Statistical Analysis
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
- Simpson Estimator of species richness and species evenness: more weight on species evenness
- unchanged
Signature 1
Needs review
Source: Figure 6b
Description: Differentially abundant taxa significantly associated with HIV infection status at 6 months postpartum.
Abundance in Group 1: increased abundance in HIV - infected
| NCBI | Quality Control | Links |
|---|---|---|
| Selenomonadaceae |
Revision editor(s): Aleru Divine
Signature 2
Needs review
Source: Figure 6b
Description: Differentially abundant taxa significantly associated with HIV infection status at 6 months postpartum.
Abundance in Group 1: decreased abundance in HIV - infected
| NCBI | Quality Control | Links |
|---|---|---|
| Romboutsia | ||
| Clostridium |
Revision editor(s): Aleru Divine
Experiment 3
Needs review
Differences from previous experiment shown
Subjects
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- The HIV-infected group consists of HIV-infected lactating women who were followed up at 6 weeks postpartum.
- Group 0 sample size Number of subjects in the control (unexposed) group
- 48
- Group 1 sample size Number of subjects in the case (exposed) group
- 25
Lab analysis
Statistical Analysis
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
- Simpson Estimator of species richness and species evenness: more weight on species evenness
- unchanged
Signature 1
Needs review
Source: Table 3
Description: Differentially abundant taxa in gut microbiota associated with inflammatory and vascular injury biomarkers after stratification by HIV infection status.
Abundance in Group 1: increased abundance in HIV - infected
| NCBI | Quality Control | Links |
|---|---|---|
| Lachnospira eligens | ||
| Oxalobacteraceae |
Revision editor(s): KateRasheed, Aleru Divine
Signature 2
Needs review
Source: Table 3
Description: Association of the gut microbiota with inflammatory and vascular injury biomarkers after stratification by HIV infection status.
Abundance in Group 1: decreased abundance in HIV - infected
| NCBI | Quality Control | Links |
|---|---|---|
| Weissella |
Revision editor(s): KateRasheed, Aleru Divine
Experiment 4
Needs review
Differences from previous experiment shown
Subjects
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- The HIV-infected group consists of HIV-infected lactating women who were followed up at 6 months postpartum.
- Group 0 sample size Number of subjects in the control (unexposed) group
- 42
- Group 1 sample size Number of subjects in the case (exposed) group
- 23
Lab analysis
Statistical Analysis
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
- Simpson Estimator of species richness and species evenness: more weight on species evenness
- unchanged
Signature 1
Needs review
Source: Table 3
Description: Differentially abundant taxa in gut microbiota associated with inflammatory and vascular injury biomarkers after stratification by HIV infection status.
Abundance in Group 1: increased abundance in HIV - infected
| NCBI | Quality Control | Links |
|---|---|---|
| Anaerotignum | ||
| Butyrivibrio | ||
| Catenibacterium | ||
| Haemophilus | ||
| Lachnospira eligens |
Revision editor(s): Aleru Divine
Signature 2
Needs review
Source: Table 3
Description: Differentially abundant taxa in gut microbiota associated with inflammatory and vascular injury biomarkers after stratification by HIV infection status.
Abundance in Group 1: decreased abundance in HIV - infected
| NCBI | Quality Control | Links |
|---|---|---|
| Actinomyces | ||
| Actinomycetota | ||
| Bacillota | ||
| Coprobacillaceae | ||
| Coriobacteriaceae | ||
| Eggerthella | ||
| Fusobacteriaceae | ||
| Lactobacillus | ||
| Solobacterium | ||
| Clostridia UCG.014Clostridia UCG.014 |
Revision editor(s): Aleru Divine
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