Gut microbiota alterations and microbial translocation in HIV/SARS-CoV-2 co-infected patients

Objective To characterize gut microbiome alterations and microbial translocation in human immunodeficiency virus (HIV)/severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) co-infected patients and identify microbial signatures associated with COVID-19 severity. Methods In this cohort study, blood and fecal samples from 38 HIV/AIDS patients (20 SARS-CoV-2 co-infected [PC group]; 18 SARS-CoV-2-negative [NC group]) were analyzed. The PC group was stratified by COVID-19 severity: mild-to-moderate (PC1, n=13), severe-to-critical (PC2, n=3), and mixed infections (PC3, n=4). Serum lipopolysaccharide (LPS), soluble CD14 (sCD14), and zonulin levels were measured to assess microbial translocation and gut barrier integrity. Fecal metagenomic profiling was performed via whole-genome shotgun sequencing (Illumina NovaSeq/HiSeq). Results Co-infected patients exhibited significantly elevated plasma LPS (78.09 vs 48.72 pg/mL, p=0.032) and sCD14 (2667 vs 1927 ng/mL, p=0.0015) compared to controls. Although no differences in α-diversity or overall taxonomic abundance were observed between the PC and NC groups, 329 PC-unique and 216 NC-unique microbial species were identified. Nine genera demonstrated diagnostic potential for co-infection [Area Under the Curve (AUC), >0.7] with Akkermansia showing the highest predictive value (AUC = 0.811). Critically, Blautia abundance was significantly reduced in severe-to-critical cases (PC2) versus mild-moderate cases (PC1, p=0.043) and controls (NC, p=0.006). Besides, our function prediction for gut microbiota suggested that SARS-CoV-2 may exacerbate lipid metabolic dysregulation in HIV-infected individuals. Conclusions HIV/SARS-CoV-2 co-infection is characterized by heightened microbial translocation and species-specific microbiota alterations rather than global dysbiosis. Blautia depletion may correlate with COVID-19 severity.