THE GASTROINTESTINAL (GI) tract serves as a major reservoir for HIV and harbours the body’s most diverse microbiome. Despite its significance, the impact of the gut bacteriome on local HIV persistence has remained largely unexplored, until now. A new study leveraging rapid autopsy samples from 24 people with HIV (PWH) in the Last Gift cohort provides compelling evidence of how gut bacterial communities influence HIV reservoirs in a segment-specific manner.
Study Design and Methods
Researchers collected 113 GI tissue samples across five segments: duodenum, jejunum, ileum, colon, and rectum. Using 16S rRNA sequencing, total HIV DNA, and msTat/Rev RNA quantification via droplet digital PCR (ddPCR), they mapped bacterial composition and HIV reservoir characteristics. Multivariable models were used to assess associations between bacterial taxa abundance and HIV DNA and transcriptional activity.
Segment-Specific HIV Reservoirs
HIV DNA levels were highest in the jejunum, intermediate in the duodenum and ileum, and lowest in the colon and rectum. Interestingly, transcriptional activity was disproportionately higher in the duodenum and ileum relative to reservoir size. These findings highlight that not all GI regions contribute equally to viral persistence and suggest specific local factors influence viral activity.
Role of the Gut Bacteriome
The study revealed significant differences in bacterial richness and composition across GI segments. Higher bacterial richness correlated with increased HIV transcription in the small bowel but decreased activity in the large bowel. Specific bacterial groups, such as short-chain fatty acid producers, mucin-degraders, and bile acid-metabolising species, were consistently linked to reduced reservoir size and activity in distal segments while enhancing transcription in proximal segments. These relationships remained robust even after accounting for antibiotic exposure, cancer status, and viral load.
Implications for HIV Cure Strategies
This research underscores the gut bacteriome’s modulatory role in HIV persistence. The segment-specific effects observed suggest that future bacteriome-based interventions should consider GI regionality to effectively target viral reservoirs. By understanding how gut bacteria interact with HIV across different GI sites, novel therapeutic strategies could be designed to reduce reservoir size and transcriptional activity, advancing efforts toward a functional HIV cure.
Reference
Trunfio M et al. HIV reservoir dynamics and bacteriome composition along the gut axis. J Infect Dis. 2025;DOI: 10.1093/infdis/jiaf546.
