Abstract
BackgroundThe microbiota plays an important role in HIV pathogenesis in humans. Microbiota can impact health through several pathways such as increasing inflammation in the gut, metabolites of bacterial origin, and microbial translocation from the gut to the periphery which contributes to systemic chronic inflammation and immune activation and the development of AIDS. Unlike HIV-infected humans, SIV-infected vervet monkeys do not experience gut dysfunction, microbial translocation, and chronic immune activation and do not progress to immunodeficiency. Here, we provide the first reported characterization of the microbial ecosystems of the gut and genital tract in a natural nonprogressing host of SIV, wild vervet monkeys from South Africa.ResultsWe characterized fecal, rectal, vaginal, and penile microbiomes in vervets from populations heavily infected with SIV from diverse locations across South Africa. Geographic site, age, and sex affected the vervet microbiome across different body sites. Fecal and vaginal microbiome showed marked stratification with three enterotypes in fecal samples and two vagitypes, which were predicted functionally distinct within each body site. External bioclimatic factors, biome type, and environmental temperature influenced microbiomes locally associated with vaginal and rectal mucosa. Several fecal microbial taxa were linked to plasma levels of immune molecules, for example, MIG was positively correlated with Lactobacillus and Escherichia/Shigella and Helicobacter, and IL-10 was negatively associated with Erysipelotrichaceae, Anaerostipes, Prevotella, and Anaerovibrio, and positively correlated with Bacteroidetes and Succinivibrio. During the chronic phase of infection, we observed a significant increase in gut microbial diversity, alterations in community composition (including a decrease in Proteobacteria/Succinivibrio in the gut) and functionality (including a decrease in genes involved in bacterial invasion of epithelial cells in the gut), and partial reversibility of acute infection-related shifts in microbial abundance observed in the fecal microbiome. As part of our study, we also developed an accurate predictor of SIV infection using fecal samples.ConclusionsThe vervets infected with SIV and humans infected with HIV differ in microbial responses to infection. These responses to SIV infection may aid in preventing microbial translocation and subsequent disease progression in vervets, and may represent host microbiome adaptations to the virus.2kSCfqxBuBxDgHDfSi19bJVideo
Highlights
The microbiota plays an important role in human immunodeficiency virus (HIV) pathogenesis in humans
During the chronic phase of infection, we observed a significant increase in gut microbial diversity, alterations in community composition and functionality, and partial reversibility of acute infection-related shifts in microbial abundance observed in the fecal microbiome
Natural composition of the microbiome in African vervets To understand the effects of SIV on the microbiome in a nonprogressing host of SIV in a natural environment, we studied the gut and genital microbial communities in the context of different geographic locations, developmental stages, sexes, and SIV infection in vervet monkeys in South Africa, by using 16S rRNA gene sequencing in 44 fecal, 103 rectal, 20 penile, and 51 vaginal microbiome samples (Supplementary Tables 1–2)
Summary
The microbiota plays an important role in HIV pathogenesis in humans. Microbiota can impact health through several pathways such as increasing inflammation in the gut, metabolites of bacterial origin, and microbial translocation from the gut to the periphery which contributes to systemic chronic inflammation and immune activation and the development of AIDS. Unlike HIV-infected humans, SIV-infected vervet monkeys do not experience gut dysfunction, microbial translocation, and chronic immune activation and do not progress to immunodeficiency. Insights into the role of the microbiota in infection have been obtained mainly from progressive hosts, which typically develop immunodeficiency upon infection. These hosts are represented by humans, in which HIV has been present on a large scale for nearly two generations, and experimentally infected Asian macaques, which are a laboratory model of pathogenic SIV infection, but are not exposed to the SIV in natura. The impact of the microbiota on the pathogenesis of the nonprogressing SIV infections in natural hosts has not been characterized to date
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