Associations Between the Gut Microbiome, Inflammation, and Cardiovascular Profiles in People With Human Immunodeficiency Virus

Abstract

Background: Inflammation and innate immune activation are associated with chronic human immunodeficiency virus (HIV) infection, despite effective treatment. Although gut microbiota alterations are linked to systemic inflammation, their relationship with HIV infection the relationships between the gut microbiome, inflammation, and HIV remains unclear.

Methods: The HIV UPBEAT Coronary Artery Disease sub-study evaluated cardiovascular disease (CVD) in people with and without HIV. Subclinical CVD was assessed using coronary computed tomography angiography (CCTA). Thirty-four biomarkers were measured using quantitative immunoassays. Stool samples underwent 16S rRNA sequencing. Differentially abundant species were identified by analysis of compositions of microbiomes with bias correction (ANCOM-BC) and correlated to biomarkers, diet, and CCTA outcomes using Spearman correlation.

Results: Among 81 participants (median age, 51 years; 73% male), people with HIV (n = 44) had higher rates of hypercholesterolemia (P < .025). Gut microbiome β-diversity differed significantly by HIV status. Enriched Bifidobacterium pseudocatenulatum, Megamonas hypermegale, and Selenomonas ruminantium correlated with lower plaque burden, while depleted Ruminococcus bromii correlated with higher plaque burden and fat intake. Depleted Bacteroides spp and Alistepes spp correlated with elevated biomarkers (D-dimer, CD40 ligand, C-reactive protein, and interferon-γ).

Conclusions: Gut microbiota differences in people with HIV were linked to subclinical CVD, diet, and inflammation, highlighting the microbiome's role in cardiovascular risk in HIV infection.

Keywords: HIV; ageing; cardiovascular disease; inflammation; microbiome.

Figure 1.

Alpha-diversity at the amplicon sequence variant level for species (A) and genus (B) for people with and without human immunodeficiency virus (HIV). Beta-diversity with Bray-Curtis dissimilarity and Jaccard similarity at the species level (C and D) and genus level (E and F), respectively. Permutational multivariate analysis of variance was performed, and the effect size for Axis 1 in the β-diversity results was interpreted using the 95% confidence interval.

Figure 2.

Differential abundance (DA) analysis of 42 species by in people with human immunodeficiency virus (HIV) compared to those without HIV. DA was assessed by analysis of compositions of microbiomes with bias correction while adjusting for the covariates based on filtered species abundance (present in at least 10% of samples and with maximum reads ≥10). False discovery rate <0.1 was considered as DA species.

Figure 3.

Heatmap showing the correlation of the differentially abundant (DA) species with mean nutrient intake and the Healthy Food Diversity (HFD) index. DA was assessed by analysis of compositions of microbiomes with bias correction while adjusting for the covariates based on filtered species abundance (present in at least 10% of samples and with maximum reads ≥10). False discovery rate <0.1 was considered as DA species. Green stars indicate *P < .05; **P < .01; ***P < .001.

Figure 4.

Heatmap showing the correlation of the differentially abundant (DA) species with the inflammatory cytokines and T-cell surface markers for people with human immunodeficiency virus (HIV) and those without HIV. DA was assessed by analysis of compositions of microbiomes with bias correction (ANCOM-BC) while adjusting for the covariates based on filtered species abundance (present in at least 10% of samples and with maximum reads ≥10). False discovery rate <0.1 was considered as DA species. Green stars indicate *P < .05; **P < .01; ***P < .001. actCD8, activated CD8 T cells; CD14, cluster of differentiation 14; ExhCD4, exhausted CD4 T cells; ExhCD8, exhausted CD8 T cells; hsCRP, high sensitivity C Reactive Protein; I-FABP, intestinal fatty acid binding protein; IFN, interferon; IL, interleukin; IL1b, interleukin 1 beta; IL1RA, IL-1 receptor antagonist; LBP, LPS binding protein; Lp-PLA2, lipoprotein-associated phospholipase A2; MCP-1, monocyte chemoattractant protein; MIP-1, macrophage inflammatory protein; sCD163, soluble cluster of differentiation 163; sCD40L, soluble CD40 ligand; s-ICAM, soluble intercellular adhesion molecule; sensCD8, sensitised CD8 T cells; TNFR, tumor necrosis factor receptor; Tregs, regulatory T cells; TSLP, thymic stromal lymphopoietin; VCAM1, vascular cell adhesion molecule; vwf, von Willebrand factor.