Distinct Gut Microbiota Signatures Associated With Progression of Atherosclerosis in People Living With Human Immunodeficiency Virus

Abstract

Abstract Background The relationship of microbiota composition dynamics and the progression of subclinical atherosclerosis in people with human immunodeficiency virus (PWH) remains unknown. Methods A 96-week, prospective, longitudinal study was performed in virologically suppressed PWH. Carotid intima-media thickness (cIMT) measurements and stool samples were obtained at baseline and at 48- and 96-week visits. cIMT progression was defined as an increase of >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 using the MiSeq platform. Results At the baseline, 48-week, and 96-week visits, 191, 190, and 167 patients, respectively, had fecal samples available for microbiome analysis. Eighty-seven participants (43%) showed atherosclerosis progression, and 54 (26.7%) presented with new carotid plaque. No significant differences were observed in adjusted α-diversity indices between groups, defined by cIMT progression. β-Diversity, determined through principal coordinate analysis, showed that the groups exhibited distinct microbial profiles (P = .03; permutational multivariate analysis of variance). Longitudinal analysis with Analysis of Compositions of Microbiomes with Bias Correction 2, adjusted for traditional cardiovascular risk factors, status as men who have sex with men, and nadir CD4 count, revealed that cIMT progression was consistently associated with Agathobacter and Ruminococcus 2, while nonprogression was consistently associated with Prevotella 7. Conclusions Progression of atherosclerosis in PWH might be associated with distinctive signatures in the gut microbiota.