The impact of western versus agrarian diet consumption on gut microbiome composition and immune dysfunction in people living with HIV in rural and urban Zimbabwe
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PROVIDER: PRJEB95999 | ENA |
REPOSITORIES: ENA
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Project description:Background: Although acquired immunodeficiency syndrome-related mortality has decreased since the introduction of antiretroviral therapy, the incidence of lung cancer in patients living with HIV (PLWH) remains high. Understanding the effects of tobacco smoke on airway gene expression in PLWH may provide insight into the elevated lung cancer risk associated with HIV. Methods: Airway epithelial brushings were collected from 12 PLWH who smoke and 19 PLWH who have never smoked and profiled using RNA-seq. Linear models were used to identify genes differentially expressed between people who smoke and have never smoked and between people who previously smoked and have never smoked. Gene set enrichment analysis was used to validate smoking-related gene signatures across datasets. Data was integrated with gene expression data from a cohort of patients without HIV to identify genes differentially modulated by both smoking and HIV status. Results: We found that previous smoking-related gene signatures are similarly associated with smoking in PLWH, including the persistent differential expression of a subset of "irreversibly altered" genes in people who previously smoked compared to people who have never smoked. We also identified and validated two gene signatures specifically modulated in people who smoke without HIV. Conclusions: Many of the effects of smoking on bronchial gene expression are shared between PLWH and non-HIV individuals. Of the subset of genes that differ between PLWH and non-HIV individuals, it appears that the effect of smoking on gene expression is more attenuated in PLWH. This includes genes related to oxidative stress and epithelial integrity, and suggests potential mechanisms that may contribute to smoking-related outcomes that are more prevalent in PLWH, such as lung cancer.
2026-02-05 | GSE318533 | GEO
Project description:The aim of this discovery case-control study was to identify patterns of differential expression of microRNAs in people living with HIV (PLWH) and assess their diagnostic value for non-alcoholic fatty liver disease (NALFD). Cases were defined as patients with severe NAFLD and controls as patients without NAFLD, characterized using the controlled attenuation parameter (CAP). Cases and controls were matched 1:1 for age, sex, body mass index, CD4+ lymphocyte count, active HCV infection, and ART regimen. Serum 2,083 simultaneous microRNA transcripts were analyzed using HTG technology and compared between cases and controls. Forty-five patients, 23 cases, and 22 controls were included in the study. In the analysis of the expression pattern of the 2,083 microRNAs, no differential expression patterns were found between both groups of patients included in the study. Analysis of the microRNA transcriptome profile of nonobese PLWH with severe NAFLD did not appear to differ from that of patients without NAFLD. Thus, microRNA might not serve as a proper biomarker for predicting severe NALFD in this population.
2023-05-03 | E-MTAB-12974 | biostudies-arrayexpress
Project description:Myeloid dendritic cells (mDC) were isolated from antiretroviral therapy (ARV)-treated and untreated people living with HIV (PLWH), and from HIV uninfected Individuals. The results indicate that mDC are altered in genes expression from PLWH. Some RNA transcriptional changes are not completely restored by ARV. This provides more data on myeloid cells, an understudied cell type, and alterations in PLWH.
2020-01-10 | GSE139559 | GEO
Project description:BackgroundThe widespread availability of antiretroviral therapy (ART) has dramatically reduced mortality and improved life expectancy for people living with HIV (PLWH). However, even with HIV-1 suppression, chronic immune activation and elevated inflammation persist and have been linked to a pro-inflammatory gut microbiome composition and compromised intestinal barrier integrity. PLWH in urban versus rural areas of sub-Saharan Africa experience differences in environmental factors that may impact the gut microbiome and immune system, in response to ART, yet this has not previously been investigated in these groups. To address this, we measured T cell activation/exhaustion/trafficking markers, plasma inflammatory markers, and fecal microbiome composition in PLWH and healthy participants recruited from an urban clinic in the city of Harare, Zimbabwe, and a district hospital that services surrounding rural villages. PLWH were either ART naïve at baseline and sampled again after 24 weeks of first-line ART and the antibiotic cotrimoxazole or were ART-experienced at both timepoints.ResultsAlthough expected reductions in the inflammatory marker IL-6, T-cell activation, and exhaustion were observed with ART-induced viral suppression, these changes were much more pronounced in the urban versus the rural area. Gut microbiome composition was the most highly altered from healthy controls in ART experienced PLWH, and characterized by both reduced alpha diversity and altered composition. However, gut microbiome composition showed a pronounced relationship with T cell activation and exhaustion in ART-naïve PLWH, suggesting a particularly significant role for the gut microbiome in disease progression in uncontrolled infection. Elevated immune exhaustion after 24 weeks of ART did correlate with both living in the rural location and a more Prevotella-rich/Bacteroides-poor microbiome type, suggesting a potential role for rural-associated microbiome differences or their co-variates in the muted improvements in immune exhaustion in the rural area.ConclusionSuccessful ART was less effective at reducing gut microbiome-associated inflammation and T cell activation in PLWH in rural versus urban Zimbabwe, suggesting that individuals on ART in rural areas of Zimbabwe may be more vulnerable to co-morbidity related to sustained immune dysfunction in treated infection. Video Abstract.
| S-EPMC10837999 | biostudies-literature
Project description:Background: Age-related comorbidities remain a burden in People living with HIV (PLWH). DNA methylation may be a link between HIV, aging, and the increased risk of lung comorbidities. Here, we investigate whether bronchoalveolar lavage (BAL) cells of PLWH demonstrate epigenome wide disruptions and advanced epigenetic aging. Methods: BAL cell DNA methylation profiles from 25 PLWH and 16 uninfected controls were tested for differential methylation of transposable elements Alu and LINE-1, a marker of aging. We used a weighted gene correlation network analysis to identify co-methylation networks associated with HIV and age. We tested the effect of HIV on DNA methylation using a robust linear model. An enrichment analysis was conducted to identify differentially methylated pathways (false discovery rate <0.10). Results: The BAL cells of PLWH were marked by global hypomethylation in both Alu and LINE-1 elements. Six co-methylated CpG networks were identified that were significantly associated with age; of these, the red module was significantly differentially methylated in PLWH and enriched pathways associated with HIV, Ras signaling, T cell receptors, and bacterial invasion of epithelial cells. We identified 6,428 differentially methylated sites associated with HIV. Conclusions: We have shown here for the first time that alterations in the DNA methylation of BAL cells (mainly macrophages) in the lung HIV show in a pattern of advanced aging. In conjunction with our findings in blood cells and airway cells, this study strongly support that HIV may contribute to increase the risk of lung comorbidities through the epigenetic regulation of aging.
2024-07-03 | GSE262656 | GEO
Project description:<p>Objective: The gut microbiome plays a pivotal role in human immunodeficiency virus (HIV) infection. However, the associated alterations in the gut microbiome-host interaction remain unclear. This study aims to investigate the gut microbiota and fecal metabolites in people living with HIV (PLWH).</p><p>Method: We collected stool samples from 70 PLWH and 34 healthy controls (HCs) and performed 16S rRNA gene sequencing. Metabolite analysis was conducted using liquid chromatography-mass spectrometry.</p><p>Results: Firmicutes, Proteobacteria, Actinobacteriota, and Bacteroidota were the most abundant phyla in both groups. At the genus level, Escherichia Shigella was significantly upregulated in the PLWH group, whereas Bacteroides were upregulated in the HC group. Functional prediction of the microbiota indicated significant reductions in alanine, aspartate, and glutamate metabolism, as well as histidine metabolism. Furthermore, comparison of fecal metabolites between the HC and PLWH groups identified 38 differentially abundant metabolites across four enriched human metabolic pathways. Spearman correlation analysis revealed close relationships between four differentially abundant microbiota members and five differentially abundant fecal metabolites, which may influence specific human metabolic pathways.</p><p>Conclusion: Our findings provide a foundation for further experimental investigations into the contribution of the gut microbiota and its associated metabolites to HIV/AIDS, offering a novel perspective for future studies on HIV/AIDS.</p>
2024-09-16 | MTBLS9264 | MetaboLights
Project description:The differential expression of metabolic genes between effector and exhausted CD8+ Tcells has been characterized in the people living with HIV (PLWH) using 768 genes from the NanoString Human Metabolic Pathways Panel.
2024-07-01 | GSE270720 | GEO
Project description:Reduced Gut Blastocystis Mediates Treatment-Associated HDL-C Increases in PLWH
| PRJEB105653 | ENA
Project description:Background: Atherosclerosis (AS)-associated cardiovascular disease is an important cause of mortality in an aging population of people living with HIV (PLWH). This elevated risk of atherosclerosis has been attributed to viral infection, prolonged usage of anti-retroviral therapy, and subsequent chronic inflammation. Methods: To investigate dysregulated immune signaling in PLWH with and without AS, we sequenced 9368 peripheral blood mononuclear cells (PBMCs) from 8 PLWH, 4 of whom also had atherosclerosis (AS+). To develop executable models of signaling pathways that drive cellular states in HIV-associated atherosclerosis, we developed the single-cell Boolean Omics Network Invariant Time Analysis (scBONITA) algorithm. ScBONITA (a) uses single-cell RNA sequencing data to infer Boolean rules for topologically characterized networks, (b) prioritizes genes based on their impact on signaling, (c) performs pathway analysis, and (d) maps sequenced cells to characteristic signaling states. We used scBONITA to identify dysregulated pathways in different cell-types from AS+ PLWH and AS- PLWH. To compare our findings with pathways associated with HIV infection, we used scBONITA to analyze a publicly available dataset of PBMCs from subjects before and after HIV infection. Additionally, the executable Boolean models characterized by scBONITA were used to analyze observed cellular states corresponding to the steady states of signaling pathways Results: We identified an increased subpopulation of CD8+ T cells and a decreased subpopulation of monocytes in AS+ PLWH. Dynamic modeling of signaling pathways and pathway analysis with scBONITA provided a new perspective on the mechanisms of HIV-associated atherosclerosis. Lipid metabolism and cell migration pathways are induced by AS rather than by HIV infection. These pathways included AGE-RAGE and PI3K-AKT signaling in CD8+ T cells, and glucagon and cAMP signaling pathways in monocytes. Further analysis of other cell subpopulations suggests that the highly interconnected PI3K-AKT signaling pathway drives cell migratory state in response to dyslipidemia. scBONITA attractor analysis mapped cells to pathway-specific signaling states that correspond to distinct cellular states. Conclusions: Dynamic network modeling and pathway analysis with scBONITA indicates that dysregulated lipid signaling regulates cell migration into the vascular endothelium in AS+ PLWH. Attractor analysis with scBONITA facilitated pathway-based characterization of cellular states that are not apparent in gene expression analyses.
2022-09-06 | GSE198339 | GEO