Ornella Sortino1,2, Nittaya Phanuphak3, Alexandra Schuetz4,5,6, Alexandra M Ortiz2, Nitiya Chomchey3, Yasmine Belkaid7,8, Jacquice Davis8, Harry A Mystakelis2, Mariam Quiñones9, Claire Deleage1, Brian Ingram10, Rungsun Rerknimitr3, Suteeraporn Pinyakorn4,5, Adam Rupert1, Merlin L Robb4,5, Jintanat Ananworanich4,5,11, Jason Brenchley2, Irini Sereti2. 1. Clinical Research Directorate, Frederick National Laboratory for Cancer Research, sponsored by the National Cancer Institute. 2. National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland. 3. SEARCH/Thai Red Cross AIDS Research Centre, Bangkok, Thailand. 4. The Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, Maryland. 5. United States Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland. 6. Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand. 7. Metaorganism Immunity Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland. 8. Microbiome Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland. 9. Bioinformatics and Computational Biosciences Branch, Office of Cyber Infrastructure and Computational Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland. 10. Metabolon, Inc., Research Triangle Park, North Carolina. 11. Department of Global Health, University of Amsterdam, Amsterdam, the Netherlands.
Abstract
Background: Intestinal microbial dysbiosis is evident in chronic HIV-infected individuals and may underlie inflammation that persists even during antiretroviral therapy (ART). It remains unclear, however, how early after HIV infection gut dysbiosis emerges and how it is affected by early ART. Methods: Fecal microbiota were studied by 16s rDNA sequencing in 52 Thai men who have sex with men (MSM), at diagnosis of acute HIV infection (AHI), Fiebig Stages 1-5 (F1-5), and after 6 months of ART initiation, and in 7 Thai MSM HIV-uninfected controls. Dysbiotic bacterial taxa were associated with relevant inflammatory markers. Results: Fecal microbiota profiling of AHI pre-ART vs HIV-uninfected controls showed a mild dysbiosis. Transition from F1-3 of acute infection was characterized by enrichment in pro-inflammatory bacteria. Lower proportions of Bacteroidetes and higher frequencies of Proteobacteria and Fusobacteria members were observed post-ART compared with pre-ART. Fusobacteria members were positively correlated with levels of soluble CD14 in AHI post-ART. Conclusions: Evidence of gut dysbiosis was observed during early acute HIV infection and was partially restored upon early ART initiation. The association of dysbiotic bacterial taxa with inflammatory markers suggests that a potential relationship between altered gut microbiota and systemic inflammation may also be established during AHI. Published by Oxford University Press on behalf of Infectious Diseases Society of America 2019.
Background: Intestinal microbial dysbiosis is evident in chronic HIV-infected individuals and may underlie inflammation that persists even during antiretroviral therapy (ART). It remains unclear, however, how early after HIV infection gut dysbiosis emerges and how it is affected by early ART. Methods: Fecal microbiota were studied by 16s rDNA sequencing in 52 Thai men who have sex with men (MSM), at diagnosis of acute HIV infection (AHI), Fiebig Stages 1-5 (F1-5), and after 6 months of ART initiation, and in 7 Thai MSM HIV-uninfected controls. Dysbiotic bacterial taxa were associated with relevant inflammatory markers. Results: Fecal microbiota profiling of AHI pre-ART vs HIV-uninfected controls showed a mild dysbiosis. Transition from F1-3 of acute infection was characterized by enrichment in pro-inflammatory bacteria. Lower proportions of Bacteroidetes and higher frequencies of Proteobacteria and Fusobacteria members were observed post-ART compared with pre-ART. Fusobacteria members were positively correlated with levels of soluble CD14 in AHI post-ART. Conclusions: Evidence of gut dysbiosis was observed during early acute HIV infection and was partially restored upon early ART initiation. The association of dysbiotic bacterial taxa with inflammatory markers suggests that a potential relationship between altered gut microbiota and systemic inflammation may also be established during AHI. Published by Oxford University Press on behalf of Infectious Diseases Society of America 2019.
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