Dataset Information

Gut Microbiome Alterations During HIV/SIV Infection: Implications for HIV Cure.

ABSTRACT: Gut mucosal damage, associated with Human Immunodeficiency Virus-1 (HIV) infection, is characterized by depletion in CD4⁺ T cells and persistent immune activation as a result of early epithelial barrier disruption and systemic translocation of microbial products. Unique approaches in studying both HIV infection in human patients and Simian Immunodeficiency Virus (SIV) infection in rhesus macaques have provided critical evidence for the pathogenesis and treatment of HIV/AIDS. While there is vast resemblance between SIV and HIV infection, the development of gut dysbiosis attributed to HIV infection in chronically infected patients has not been consistently reported in SIV infection in the non-human primate model of AIDS, raising concerns for the translatability of gut microbiome studies in rhesus macaques. This review outlines our current understanding of gut microbial signatures across various stages of HIV versus SIV infection, with an emphasis on the impact of microbiome-based therapies in restoring gut mucosal immunity as well as their translational potential to supplement current HIV cure efforts.

SUBMITTER: Crakes KR

PROVIDER: S-EPMC6539195 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Gut Microbiome Alterations During HIV/SIV Infection: Implications for HIV Cure.

Crakes Katti R KR Jiang Guochun G

Frontiers in microbiology 20190522

Gut mucosal damage, associated with Human Immunodeficiency Virus-1 (HIV) infection, is characterized by depletion in CD4<sup>+</sup> T cells and persistent immune activation as a result of early epithelial barrier disruption and systemic translocation of microbial products. Unique approaches in studying both HIV infection in human patients and Simian Immunodeficiency Virus (SIV) infection in rhesus macaques have provided critical evidence for the pathogenesis and treatment of HIV/AIDS. While the ...[more]

PMID: 31191468

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Project description:Pharyngeal gonorrhoea is a common sexually transmitted infection among 'men having sex with other men' (MSM). Neisseria gonorrhoeae (NG) pharyngeal infections are usually characterized by the absence of symptoms, acting as an important reservoir for their further spread. To the best of our knowledge, no information about the composition of the pharyngeal microbiome during an ongoing NG infection is currently available. Therefore, in this study, we characterized the pharyngeal bacterial community profiles associated with NG infection in a well-selected cohort of HIV-negative MSM reporting unsafe oral intercourse. A total of 70 pharyngeal swabs were considered, comparing non-infected subjects (n = 45) versus patients with pharyngeal gonorrhoea (n = 25) whose microbiota composition was analyzed from pharyngeal swabs through sequencing of hypervariable V3-V4 regions of the 16S rRNA gene. The pharyngeal microbiome of all subjects was dominated by Prevotellaceae, Veillonellaceae and Streptococcaceae families. Patients with pharyngeal gonorrhoea harboured a pharyngeal microbiome quite similar to negative subjects. Nevertheless, when looking to less-represented bacterial species (relative abundance approximately 1% or less), an imbalance between aerobe and anaerobe microorganisms was observed in NG-infected patients. In particular, the pharyngeal microbiome of NG-positive individuals was richer in several anaerobes (e.g. Treponema, Parvimonas, Peptococcus, Catonella, Filifactor) and poorer in various aerobe genera (i.e. Pseudomonas, Escherichia), compared to non-infected controls. No significant differences were noticed in the distribution of commensal Neisseria species of the oropharynx between NG-positive and negative subjects. Metabolic variations induced by changes in the microbiome abundance were assessed by a functional prediction of the bacterial metabolic pathways: a more abundant involvement of D-glutamine and D-glutamate metabolism, carbohydrate metabolism, as well as a greater activation of the energy metabolism was observed in patients with pharyngeal gonorrhoea compared to non-infected individuals. Information about the bacterial composition of the pharyngeal microbiome in case of gonorrhoea could shed light on the pathogenesis of the infection and open new perspectives for the prevention and control of this condition.

Project description: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. Video Abstract.

Project description:Background: Many studies have explored changes in the gut microbiome associated with HIV infection, but the consistent pattern of changes has not been clarified. Men who have sex with men (MSM) are very likely to be an independent influencing factor of the gut microbiome, but relevant research is still lacking. Methods: We conducted a meta-analysis by screening 12 published studies of 16S rRNA gene amplicon sequencing of gut microbiomes related to HIV/AIDS (six of these studies contain data that is relevant and available to MSM) from NCBI and EBI databases. The analysis of gut microbiomes related to HIV infection status and MSM status included 1,288 samples (HIV-positive (HIV+) individuals, n = 744; HIV-negative (HIV-) individuals, n = 544) and 632 samples (MSM, n = 328; non-MSM, n = 304), respectively. The alpha diversity indexes, beta diversity indexes, differentially enriched genera, differentially enriched species, and differentially enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) functional pathways related to gut microbiomes were calculated. Finally, the overall trend of the above indicators was evaluated. Results: Our results indicate that HIV+ status is associated with decreased alpha diversity of the gut microbiome. MSM status is an important factor that affects the study of HIV-related gut microbiomes; that is, MSM are associated with alpha diversity changes in the gut microbiome regardless of HIV infection, and the changes in the gut microbiome composition of MSM are more significant than those of HIV+ individuals. A consistent change in Bacteroides caccae, Bacteroides ovatus, Bacteroides uniformis, and Prevotella stercorea was found in HIV+ individuals and MSM. The differential expression of the gut microbiome may be accompanied by changes in functional pathways of carbohydrate metabolism, amino acid metabolism, and lipid Metabolism. Conclusions: This study shows that the changes in the gut microbiome are related to HIV and MSM status. Importantly, MSM status may have a far greater impact on the gut microbiome than HIV status.

Dataset Information

Gut Microbiome Alterations During HIV/SIV Infection: Implications for HIV Cure.

Publications

Gut Microbiome Alterations During HIV/SIV Infection: Implications for HIV Cure.

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