Distinct gut microbiota signatures associated with progression of atherosclerosis in people living with HIV

Abstract

Background: The relationship of microbiota composition dynamics and the progression of subclinical atherosclerosis in people with HIV (PWH) remains unknown.

Methods: 96-week, prospective, longitudinal study in virologically-suppressed PWH. Carotid intima-media thickness (cIMT) measurements and stool samples were obtained at baseline, 48-week and 96-week visits. cIMT progression was defined as an increase >10% and/or detection of new carotid plaque. To profile the gut microbiome, amplification and sequencing of 16S ribosomal-RNA (V3-V4 variable regions) were carried out following the Illumina protocol. Sequencing was performed with MiSeq platform.

Results: 191, 190 and 167 patients had available fecal samples for microbiome analysis at the baseline, 48- and 96-week visits, respectively. 87 (43%) participants showed atherosclerosis progression, and 54 (26.7%) presented new carotid plaque. No significant differences were observed in adjusted α-diversity indices between groups defined by cIMT progression. Beta-diversity determined through principal coordinate analysis distances showed that the groups exhibited distinct microbial profiles (PERMANOVA p-value = 0.03). Longitudinal analysis with ANCOM-BC2 adjusted for traditional cardiovascular risk factors, MSM and nadir CD4 count revealed that cIMT progression was consistently associated with Agathobacter and Ruminococcus_2, while non-progression was consistently associated with Prevotella_7.

Conclusion: Progression of atherosclerosis in PWH might be associated with distinctive signatures in the gut microbiota.

Keywords: HIV; atherogenesis; atherosclerosis progression; cardiovascular disease; cardiovascular events; carotid intima-media thickness; carotid plaque; microbiome; microbiota; subclinical atherosclerosis.