Microbiome Stability with Chronic SIV Infection in AIDS-resistant Sooty Mangabeys

Abstract

Sooty mangabeys (SMs) are a natural host species of simian immunodeficiency virus (SIV) and avoid acquired immune deficiency syndrome (AIDS) despite persistently high viral loads, making them a pivotal research model for HIV pathogenesis. Unlike pathogenic SIV infection of macaque species, or HIV infection of humans, SIV-infected SMs maintain gastrointestinal barrier integrity. Here, we characterize the gastrointestinal bacterial microbiota of SIV-infected and uninfected SMs and perform a comparative analysis of diet-matched, rhesus macaques (RM). We assessed the fecal microbiome in fifty SM and thirty RM in total, and conducted analyses of the effect of SIV-status, species, and housing. When examining indoor-outdoor and indoor-only housing in our SM cohorts, biodiversity reduction and mild phylogenetic taxonomic perturbances were present. No statistically relevant differences were seen for biodiversity richness and evenness, or phylogenetic taxonomic communities between SIV negative and positive SM cohorts. In contrast, with pathogenic early chronic SIV infections in RM a trend of alpha diversity loss and increase of beta diversity and few phyla taxonomic communities differed. Lastly, we observed lower levels of pathobiont bacterial communities in SIV-uninfected SMs relative to RMs. These data suggest that the pre-existing bacterial community structure may contribute to the divergent phenotype between SIV natural hosts and pathogenic macaque species.\n\nImportanceHuman immunodeficiency virus remains a global concern. The sooty mangabey (SM) monkey is an important biomedical research model for understanding HIV pathogenesis due to its ability to avoid AIDS disease progression despite high viremia. In people living with HIV, gastrointestinal dysbiosis towards enrichment of pathobiont communities has been frequently reported. In this study we characterized the fecal microbiota of a primate non-pathogenic SIV host, the SM, and made direct comparisons to a pathogenic SIV host species, the rhesus macaque. We observed that SMs exhibit stability of the microbiota community into chronic SIV infection, which contrasts with SIV-infected rhesus macaques, in which we observed bacterial community divergence relative to uninfected animals. Collectively, our observation of stabilization of beneficent taxa in the mucosa of AIDS-resistant primates suggests that therapeutic strategies to enrich these communities may have potential for ameliorating the gastrointestinal inflammation in people living with HIV.