HIV Reservoir Dynamics and Bacteriome Composition Along the Gut Axis

作者：Mattia Trunfio, Davey M. Smith, Noah C. Gaitan, M.M. Awad, Magali Porrachia, Annie Wells, Jesús Rivera–Nieves, Elizabeth Hastie, Patricia K. Riggs, Sara Gianella, Antoine Chaillon · 发表于：The Journal of Infectious Diseases · 年份：2025 · DOI：10.1093/infdis/jiaf546 · 被引用次数：4 · 研究领域：Gut microbiota and health、Bacteriophages and microbial interactions、HIV Research and Treatment

BACKGROUND: The gastrointestinal (GI) tract is a major reservoir of HIV and home to the body's most diverse microbiome. However, the role of the gut bacteriome in modulating local HIV persistence remains uninvestigated. METHODS: Leveraging rapid autopsy samples (n = 113) from 24 people with HIV in the Last Gift cohort, we performed 16S rRNA sequencing and quantified total HIV DNA and multiply spliced Tat/Rev RNA (droplet digital polymerase chain reaction) across 5 GI segments: duodenum, jejunum, ileum, colon, and rectum. Associations between the relative abundance of bacterial taxa and reservoir characteristics were analyzed via multivariable models. RESULTS: HIV DNA levels were highest in the jejunum, intermediate in the duodenum and ileum, and lowest in the colon and rectum (P < .05 for all). HIV transcriptional activity was higher than expected relative to the reservoir size in the duodenum and ileum. Bacterial communities significantly differed in richness and composition across the segments (permutational multivariate analysis of variance, P = .002). Higher richness was associated with increased HIV transcriptional activity in the small bowel (ρ = 0.32, P = .015) and decreased activity in the large bowel (ρ = -0.41, P = .013). Segment-specific associations between taxa and HIV reservoir were observed: among these, short-chain fatty acid producers, mucin degraders, and bile acid metabolizers were consistently associated with reduced reservoir size and activity in the larg...