关键词: HIV感染者, 高通量测序, 细菌, 噬菌体, α多样性, Spearman相关性

Abstract: Objective To compare the composition of plasma bacteria and phages between healthy individuals and individuals with HIV infection, and to investigate the differential correlations between phages and bacteria within these two cohorts. Methods Blood samples were collected from a cohort of HIV-infected individuals and a control group of healthy individuals. Nucleic acids were extracted for metagenomic sequencing. Bioinformatic pipelines were utilized to identify bacterial and phage compositions and to predict phage-host relationships. Alpha diversity analyses were conducted to assess microbial diversity and richness. Spearman's rank correlation was employed to analyze the interrelationships between phages and bacteria. Results This study enrolled 61 individuals with HIV infection and 15 healthy controls. In the healthy cohort, 267 bacterial species, 146 genera, and 91 families were identified, whereas the HIV-infected cohort presented 294 bacterial species, 165 genera, and 103 families. The two groups shared 9 families, 8 genera, and 6 species. Alpha diversity analysis revealed no significant difference in plasma bacterial diversity (Shannon index, P=0.081) between the groups; however, bacterial richness (Chao1 index) was significantly higher in the healthy controls compared to the HIV-infected individuals (P=3.7×10⁻⁶). Phages were detected in all healthy controls, with 165 phage species and 102 genera identified. Conversely, phages were detected in only 46 of the 61 HIV-infected participants (75.41%), comprising 61 phage species and 34 genera. Alpha diversity metrics for the plasma phageome were significantly higher in the healthy cohort in terms of both diversity (Shannon index, P=1.8×10⁻⁸) and richness (Chao1 index, P=9.1×10⁻⁹). The three most abundant phages in both groups were identified as those associated with the genera Rhodoferax, Cronobacter, and Cutibacterium. In the HIV-infected cohort, phages associated with Cronobacter, Rhodoferax, and Flavobacterium demonstrated significant negative or positive correlations with plasma levels of Lactobacillus, Cupriavidus, and Citrobacter, respectively (all P<0.05). These correlations, however, were attenuated or exhibited an opposite trend in the healthy control group. Conclusion Marked differences exist in the plasma microbial composition of healthy individuals versus those with HIV infection, particularly concerning the diversity, richness, and bacterium-phage correlations of the phageome. HIV infection may substantially reshape the plasma phage community, thereby potentially affecting the stability of the blood micro-ecosystem.

Key words: HIV infection, High-throughput sequencing, Bacteria, Phages, Alpha diversity, Spearman′s rank correlation