Abnormal blood microbiota profiles are associated with inflammation and immune restoration in HIV/AIDS individuals

Although gut microbiota alteration and related blood microbe profiles in human immunodeficiency virus (HIV)-infected individuals are associated with the disease progression, how abnormal blood microbe profiles influence the inflammation and immune restoration are not fully understood. To address these issues, this study enrolled 24 healthy controls (HCs) and 91 HIV-infected individuals, including 30 treatment-naive individuals (TNs), 31 immunological non-responders (INRs), and 30 immunological responders (IRs); subsequently, we analyzed blood microbe profiles using metagenomic sequencing and Olink proteomics technology, and identify inflammation-related proteins in peripheral blood samples of these individuals. The results showed increased translocation of microbes in the blood of TNs. This translocation did not return to normal level in either IRs or INRs who received antiretroviral therapy. In addition, Porphyromonas gingivalis significantly increased in TNs, IRs, and INRs compared to HCs. P. gingivalis was inversely associated with CD4(+) T-cell counts, CD4/CD8 ratio, latency-associated peptide transforming growth factor-beta 1, and tumor necrosis factor-related activation-induced cytokine (TRANCE) and positively associated with HIV reservoirs. Burkholderia multivorans and Bacillus thuringiensis significantly decreased in TNs, IRs, and INRs compared to HCs and were positively associated with CD4(+) T-cell counts and the CD4/CD8 ratio and negatively associated with HIV reservoir size and pro-inflammatory factors. We identified several species of microbes that were associated with CD4(+) T-cell restoration on antiretroviral therapy, Prevotella sp. CAG:5226, Eubacterium sp. CAG:251, Phascolarctobacterium succinatutens, Anaerobutyricum hallii, Prevotella sp. AM34-19LB, and Phocaeicola plebeius were positively associated with HIV reservoir size and pro-inflammatory proteins. Another group of bacteria, B. multivorans, B. thuringiensis, Vibrio vulnificus, and Acinetobacter baumannii, which were negatively associated and pro-inflammatory proteins. In conclusion, different microbes within blood of HIV-infected individuals were found to be closely associated with persistent inflammation and immune restoration, suggesting the blood microbe profiles of HIV-infected individuals also influence disease progression. IMPORTANCE The characteristics of blood microbiota in HIV-infected individuals and their relevance to disease progression are still unknown, despite alterations in gut microbiota diversity and composition in HIV-infected individuals. Here, we present evidence of increased blood microbiota diversity in HIV-infected individuals, which may result from gut microbiota translocation. Also, we identify a group of microbes, Porphyromonas gingivalis, Prevotella sp. CAG:5226, Eubacterium sp. CAG:251, Phascolarctobacterium succinatutens, Anaerobutyricum hallii, Prevotella sp. AM34-19LB, and Phocaeicola plebeius, which are linked to poor immunological recovery. This work provides a scientific foundation toward therapeutic strategies targeting blood microbiota for immune recovery of HIV infection.