Association Between Gut Microbiota and HIV Infection Risk: Insights from Mendelian Randomization and 16S rRNA Amplicon Sequencing

Observational evidence links gut microbiota (GM) dysbiosis to HIV infection; however, the causal relationship between them has not been established. Mendelian randomization (MR) and 16S rRNA gene sequencing analyses were performed to identify gut microbial taxa associated with HIV infection risk. MR analysis results identified 18 gut microbial taxa associated with HIV infection (<i>p</i> values < 0.05), of which 16 taxa were detected in the 16S rRNA gene sequencing data. Following the exclusion of seven taxa with low relative abundance, eight taxa with potential relationships with HIV infection were detected in the 16S rRNA gene sequencing data. Four taxa (Clostridia class, Erysipelotrichales order, <i>Paraprevotella</i> genus, and <i>Parabacteroides distasonis</i> species) showed negative associations and four others (Proteobacteria phylum, <i>Coriobacteriaceae</i> family, <i>Subdoligranulum</i> genus, and <i>Bacteroides ovatus</i> species) showed positive associations with HIV infection risk. The eight taxa effectively distinguished between healthy controls (HCs) and people with HIV (PWH) (<i>p</i> values < 0.05). The area under the curve (AUC) values for the ROC curve analysis ranged from 0.62 to 0.87 for differentiating the HC and PWH groups. Furthermore, the effect of <i>Ruminococcus callidus</i> on HIV infection was partially mediated by hypoxanthine, exhibiting a mediated effect β of 0.17 (<i>p</i> = 0.042). These findings highlight the important role of the GM in HIV infection risk, facilitating future studies exploring better GM regulation strategies against HIV infection risk.