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.
Highlights
The human gut is home to a vast community of bacterial mutualist[1]
The composition of gut microbiota in macaques is slightly different from humans[6], one could argue that observed changes of gut microbiomes from the nonhuman primate (NHP) model, if occurred, can still provide important information related to the microbiome dynamics due to HIV/SIV infection and antiretroviral therapy (ART)
We found that the macaque gut microbiota had altered taxonomic composition between SIV+ and ART groups, as well as among different treatment periods, paralleling human studies
Summary
The human gut is home to a vast community of bacterial mutualist[1]. It plays an important role in rapid and longterm protection against pathogens. Studies reported that the alterations in the gut microbiome and changes in dietary tryptophan catabolite by-product are associated with systemic immune activation, which contributes to the disease progression[17,18]. The nonhuman primate (NHP) model of SIV infection and ART is instrumental in many aspects of HIV research. The composition of gut microbiota in macaques is slightly different from humans[6], one could argue that observed changes of gut microbiomes from the NHP model, if occurred, can still provide important information related to the microbiome dynamics due to HIV/SIV infection and ART. We used the rhesus macaque model of HIV infection to characterize the gut microbial community and compared microbiome composition in groups of healthy animals (NON_SIV), SIV-infected animals (SIV+), and SIVinfected animals receiving antiretroviral therapy (ART). Our goal was to analyze the impact of ART on dynamic changes and restoration of normal gut microbiota upon SIV infection
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