Immune activation and inflammation in lactating women on combination antiretroviral therapy: role of gut dysfunction and gut microbiota imbalance

Study information

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Reviewed Marked as Reviewed by Svetlana up on 2024-11-5

study design

time series / longitudinal observational

Citation

PMID PubMed identifier for scientific articles.

38045684

DOI Digital object identifier for electronic documents.

10.3389/fimmu.2023.1280262

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

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Reviewed Marked as Reviewed by ChiomaBlessing on 2024-11-5

Curated date: 2024/10/02

Curator: Paavni Goyal

Revision editor(s): WikiWorks, Aleru Divine, Paavni Goyal, KateRasheed

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

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

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Reviewed Marked as Reviewed by ChiomaBlessing on 2024-11-5

Curated date: 2024/10/02

Curator: Paavni Goyal

Revision editor(s): WikiWorks, Aleru Divine, Paavni Goyal, KateRasheed

Source: Figure 6a

Description: Differentially abundant taxa significantly associated with HIV infection status at 6 weeks postpartum.

Abundance in Group 1: increased abundance in HIV - infected

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Collinsella
Coriobacteriales
Micrococcaceae
Slackia

Revision editor(s): WikiWorks, Aleru Divine, Paavni Goyal, KateRasheed

Signature 2

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Reviewed Marked as Reviewed by ChiomaBlessing on 2024-11-5

Curated date: 2024/10/02

Curator: Paavni Goyal

Revision editor(s): WikiWorks, Aleru Divine, Paavni Goyal, KateRasheed

Source: Figure 6a

Description: Differentially abundant taxa significantly associated with HIV infection status at 6 weeks postpartum.

Abundance in Group 1: decreased abundance in HIV - infected

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Clostridiaceae
Clostridium

Revision editor(s): WikiWorks, Aleru Divine, Paavni Goyal, KateRasheed

Experiment 2

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Reviewed Marked as Reviewed by ChiomaBlessing on 2024-11-5

Curated date: 2024/10/19

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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

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Curated date: 2024/10/20

Curator: Aleru Divine

Revision editor(s): Aleru Divine, WikiWorks

Source: Figure 6b

Description: Differentially abundant taxa significantly associated with HIV infection status at 6 months postpartum.

Abundance in Group 1: increased abundance in

NCBI	Quality Control	Links
Selenomonadaceae

Revision editor(s): Aleru Divine, WikiWorks

Signature 2

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Curated date: 2024/10/20

Curator: Aleru Divine

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Source: Figure 6b

Description: Differentially abundant taxa significantly associated with HIV infection status at 6 months postpartum.

Abundance in Group 1: decreased abundance in

NCBI	Quality Control	Links
Romboutsia
Clostridium

Revision editor(s): Aleru Divine, WikiWorks

Experiment 3

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Reviewed Marked as Reviewed by ChiomaBlessing on 2024-11-5

Curated date: 2024/10/20

Curator:

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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

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Mark reviewed

Your review change was submitted

Needs review

Curated date: 2024/10/20

Curator: KateRasheed

Revision editor(s): KateRasheed, Aleru Divine, WikiWorks

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

NCBI	Quality Control	Links
Lachnospira eligens
Oxalobacteraceae

Revision editor(s): KateRasheed, Aleru Divine, WikiWorks

Signature 2

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Curated date: 2024/10/21

Curator: KateRasheed

Revision editor(s): KateRasheed, Aleru Divine, WikiWorks

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

NCBI	Quality Control	Links
Weissella

Revision editor(s): KateRasheed, Aleru Divine, WikiWorks

Experiment 4

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Reviewed Marked as Reviewed by ChiomaBlessing on 2024-11-5

Curated date: 2024/10/21

Curator: Aleru Divine

Revision editor(s): Aleru Divine, WikiWorks

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

EditHistoryDelete

Mark reviewed

Your review change was submitted

Needs review

Curated date: 2024/10/21

Curator: Aleru Divine

Revision editor(s): Aleru Divine, WikiWorks

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, WikiWorks

Signature 2

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Curated date: 2024/10/21

Curator: Aleru Divine

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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, WikiWorks