Associations between the gut microbiome, inflammation and cardiovascular profiles in people with HIV.

Abstract

Background: Inflammation and innate immune activation are associated with chronic HIV infection, despite effective treatment. Although gut microbiota alterations are linked to systemic inflammation, the relationships between the gut microbiome, inflammation and HIV remain unclear.

Methods: The UPBEAT-CAD sub-study, examining cardiovascular disease (CVD) risk in HIV, enrolled participants matched on HIV status and traditional CVD risk factors. Subclinical CVD was assessed using coronary computed tomography angiography (CCTA). 34 biomarkers were measured using quantitative immunoassays. Microbiota composition was analysed by 16S rRNA sequencing of stool samples, with taxonomic assignment via the SPINGO pipeline. 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 , 54%) had a higher prevalence of hypercholesterolaemia (p <0.025) and statin use (p <0.001). A significant separation in gut microbiome β-diversity was observed between people with and without HIV. ANCOM-BC analysis identified 42 differentially abundant species and 10 genera in those with HIV. Enrichment of Bifidobacterium pseudocatenulatum, Megamonas hypermegale and Selenomonas ruminantium and depletion of Fusicatenenibacter correlated with lower plaque burden. Depletion of SCFA-producing Ruminococcus bromii correlated with higher plaque burden and fat intake, while depletion of Bacteroides spp and Alistepes spp correlated with elevated inflammatory biomarkers (D-dimer, CD40-ligand, CRP and IFN-γ).

Conclusion: Significant gut microbiota differences in people with HIV were linked to subclinical CVD, diet, and inflammation, suggesting a role for the microbiome in cardiovascular risk in HIV infection.