Alterations of the gut bacterial microbiota in rhesus macaques with SIV infection and on short- or long-term antiretroviral therapy

Abstract

Gut dysbiosis and microbial translocation are associated with chronic systemic immune activation and inflammation in HIV-1 infection. However, the extent of restoration of gut microbiota in HIV-1 patients with short or long-term antiretroviral therapy (ART) is unclear. To understand the impact of ART on the gut microbiota, we used the rhesus macaque model of SIV infection to characterize and compare the gut microbial community upon SIV infection and during ART. We observed altered taxonomic compositions of gut microbiota communities upon SIV infection and at different time points of ART. SIV-infected animals showed decreased diversity of gut microbiome composition, while the ART group appeared to recover towards the diversity level of the healthy control. Animals undergoing ART for various lengths of time were observed to have differential gut bacterial abundance across different time points. In addition, increased blood lipopolysaccharide (LPS) levels during SIV infection were reduced to near normal upon ART, indicating that microbial translocation and immune activation can be improved during therapy. In conclusion, while short ART may be related to transient increase of certain pathogenic bacterial microbiome, ART may promote microbiome diversity compromised by SIV infection, improve the gut microbiota towards the healthy compositions and alleviate immune activation.