Gut microbiota diversity predicts immune status in HIV-1 infection

OBJECTIVE:HIV-1 infection is characterized by altered intestinal barrier, gut microbiota dysbiosis, and systemic inflammation. We hypothesized that changes of the gut microbiota predict immune dysfunction and HIV-1 progression, and that antiretroviral therapy (ART) partially restores the microbiota...

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Veröffentlicht in:AIDS (London) 2015-11, Vol.29 (18), p.2409-2418
Hauptverfasser: Nowak, Piotr, Troseid, Marius, Avershina, Ekatarina, Barqasho, Babilonia, Neogi, Ujjwal, Holm, Kristian, Hov, Johannes R, Noyan, Kajsa, Vesterbacka, Jan, Svärd, Jenny, Rudi, Knut, Sönnerborg, Anders
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container_end_page 2418
container_issue 18
container_start_page 2409
container_title AIDS (London)
container_volume 29
creator Nowak, Piotr
Troseid, Marius
Avershina, Ekatarina
Barqasho, Babilonia
Neogi, Ujjwal
Holm, Kristian
Hov, Johannes R
Noyan, Kajsa
Vesterbacka, Jan
Svärd, Jenny
Rudi, Knut
Sönnerborg, Anders
description OBJECTIVE:HIV-1 infection is characterized by altered intestinal barrier, gut microbiota dysbiosis, and systemic inflammation. We hypothesized that changes of the gut microbiota predict immune dysfunction and HIV-1 progression, and that antiretroviral therapy (ART) partially restores the microbiota composition. DESIGN:An observational study including 28 viremic patients, three elite controllers, and nine uninfected controls. Blood and stool samples were collected at baseline and for 19 individuals at follow-up (median 10 months) during ART. METHODS:Microbiota composition was determined by 16S rRNA sequencing (Illumina MiSeq). Soluble markers of microbial translocation and monocyte activation were analyzed by Limulus Amebocyte Lysate assay or ELISA. RESULTS:Several alpha-diversity measures, including number of observed bacterial species and Shannon index, were significantly lower in viremic patients compared to controls. The alpha diversity correlated with CD4 T-cell counts and inversely with markers of microbial translocation and monocyte activation. In multivariate linear regression, for every age and sex-adjusted increase in the number of bacterial species, the CD4 T-cell count increased with 0.88 (95% confidence interval 0.35–1.41) cells/μl (P = 0.002). After introduction of ART, microbiota alterations persisted with further reduction in alpha diversity. The microbiota composition at the genus level was profoundly altered in viremic patients, both at baseline and after ART, with Prevotella reduced during ART (P 
doi_str_mv 10.1097/QAD.0000000000000869
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We hypothesized that changes of the gut microbiota predict immune dysfunction and HIV-1 progression, and that antiretroviral therapy (ART) partially restores the microbiota composition. DESIGN:An observational study including 28 viremic patients, three elite controllers, and nine uninfected controls. Blood and stool samples were collected at baseline and for 19 individuals at follow-up (median 10 months) during ART. METHODS:Microbiota composition was determined by 16S rRNA sequencing (Illumina MiSeq). Soluble markers of microbial translocation and monocyte activation were analyzed by Limulus Amebocyte Lysate assay or ELISA. RESULTS:Several alpha-diversity measures, including number of observed bacterial species and Shannon index, were significantly lower in viremic patients compared to controls. The alpha diversity correlated with CD4 T-cell counts and inversely with markers of microbial translocation and monocyte activation. In multivariate linear regression, for every age and sex-adjusted increase in the number of bacterial species, the CD4 T-cell count increased with 0.88 (95% confidence interval 0.35–1.41) cells/μl (P = 0.002). After introduction of ART, microbiota alterations persisted with further reduction in alpha diversity. The microbiota composition at the genus level was profoundly altered in viremic patients, both at baseline and after ART, with Prevotella reduced during ART (P &lt; 0.007). CONCLUSIONS:Gut microbiota alterations are closely associated with immune dysfunction in HIV-1 patients, and these changes persist during short-term ART. Our data implicate that re-shaping the microbiota may be an adjuvant therapy in patients commencing successful ART.</description><identifier>ISSN: 0269-9370</identifier><identifier>EISSN: 1473-5571</identifier><identifier>DOI: 10.1097/QAD.0000000000000869</identifier><identifier>PMID: 26355675</identifier><language>eng</language><publisher>England: Copyright Wolters Kluwer Health, Inc</publisher><subject>Adult ; Aged ; AIDS/HIV ; Bacterial Translocation ; Cohort Studies ; DNA, Bacterial - chemistry ; DNA, Bacterial - genetics ; DNA, Ribosomal - chemistry ; DNA, Ribosomal - genetics ; Dysbiosis ; Enzyme-Linked Immunosorbent Assay ; Female ; Gastrointestinal Microbiome ; HIV Infections - immunology ; HIV Infections - virology ; HIV-1 - isolation &amp; purification ; Human immunodeficiency virus 1 ; Humans ; Lentivirus ; Limulus Test ; Male ; Microbiota ; Middle Aged ; Molecular Sequence Data ; Prevotella ; RNA, Ribosomal, 16S - genetics ; Sequence Analysis, DNA ; Young Adult</subject><ispartof>AIDS (London), 2015-11, Vol.29 (18), p.2409-2418</ispartof><rights>Copyright © 2015 Wolters Kluwer Health, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5489-a2304c11dc05398b368426909fdf40bdbf8b5c928fc59e594eed6a109452b6903</citedby><cites>FETCH-LOGICAL-c5489-a2304c11dc05398b368426909fdf40bdbf8b5c928fc59e594eed6a109452b6903</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26355675$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttp://kipublications.ki.se/Default.aspx?queryparsed=id:132802820$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><creatorcontrib>Nowak, Piotr</creatorcontrib><creatorcontrib>Troseid, Marius</creatorcontrib><creatorcontrib>Avershina, Ekatarina</creatorcontrib><creatorcontrib>Barqasho, Babilonia</creatorcontrib><creatorcontrib>Neogi, Ujjwal</creatorcontrib><creatorcontrib>Holm, Kristian</creatorcontrib><creatorcontrib>Hov, Johannes R</creatorcontrib><creatorcontrib>Noyan, Kajsa</creatorcontrib><creatorcontrib>Vesterbacka, Jan</creatorcontrib><creatorcontrib>Svärd, Jenny</creatorcontrib><creatorcontrib>Rudi, Knut</creatorcontrib><creatorcontrib>Sönnerborg, Anders</creatorcontrib><title>Gut microbiota diversity predicts immune status in HIV-1 infection</title><title>AIDS (London)</title><addtitle>AIDS</addtitle><description>OBJECTIVE:HIV-1 infection is characterized by altered intestinal barrier, gut microbiota dysbiosis, and systemic inflammation. We hypothesized that changes of the gut microbiota predict immune dysfunction and HIV-1 progression, and that antiretroviral therapy (ART) partially restores the microbiota composition. DESIGN:An observational study including 28 viremic patients, three elite controllers, and nine uninfected controls. Blood and stool samples were collected at baseline and for 19 individuals at follow-up (median 10 months) during ART. METHODS:Microbiota composition was determined by 16S rRNA sequencing (Illumina MiSeq). Soluble markers of microbial translocation and monocyte activation were analyzed by Limulus Amebocyte Lysate assay or ELISA. RESULTS:Several alpha-diversity measures, including number of observed bacterial species and Shannon index, were significantly lower in viremic patients compared to controls. The alpha diversity correlated with CD4 T-cell counts and inversely with markers of microbial translocation and monocyte activation. In multivariate linear regression, for every age and sex-adjusted increase in the number of bacterial species, the CD4 T-cell count increased with 0.88 (95% confidence interval 0.35–1.41) cells/μl (P = 0.002). After introduction of ART, microbiota alterations persisted with further reduction in alpha diversity. The microbiota composition at the genus level was profoundly altered in viremic patients, both at baseline and after ART, with Prevotella reduced during ART (P &lt; 0.007). CONCLUSIONS:Gut microbiota alterations are closely associated with immune dysfunction in HIV-1 patients, and these changes persist during short-term ART. 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purification</topic><topic>Human immunodeficiency virus 1</topic><topic>Humans</topic><topic>Lentivirus</topic><topic>Limulus Test</topic><topic>Male</topic><topic>Microbiota</topic><topic>Middle Aged</topic><topic>Molecular Sequence Data</topic><topic>Prevotella</topic><topic>RNA, Ribosomal, 16S - genetics</topic><topic>Sequence Analysis, DNA</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Nowak, Piotr</creatorcontrib><creatorcontrib>Troseid, Marius</creatorcontrib><creatorcontrib>Avershina, Ekatarina</creatorcontrib><creatorcontrib>Barqasho, Babilonia</creatorcontrib><creatorcontrib>Neogi, Ujjwal</creatorcontrib><creatorcontrib>Holm, Kristian</creatorcontrib><creatorcontrib>Hov, Johannes R</creatorcontrib><creatorcontrib>Noyan, Kajsa</creatorcontrib><creatorcontrib>Vesterbacka, Jan</creatorcontrib><creatorcontrib>Svärd, Jenny</creatorcontrib><creatorcontrib>Rudi, Knut</creatorcontrib><creatorcontrib>Sönnerborg, Anders</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Health and Safety Science Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Safety Science and Risk</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>SwePub</collection><collection>SwePub Articles</collection><jtitle>AIDS (London)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Nowak, Piotr</au><au>Troseid, Marius</au><au>Avershina, Ekatarina</au><au>Barqasho, Babilonia</au><au>Neogi, Ujjwal</au><au>Holm, Kristian</au><au>Hov, Johannes R</au><au>Noyan, Kajsa</au><au>Vesterbacka, Jan</au><au>Svärd, Jenny</au><au>Rudi, Knut</au><au>Sönnerborg, Anders</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Gut microbiota diversity predicts immune status in HIV-1 infection</atitle><jtitle>AIDS (London)</jtitle><addtitle>AIDS</addtitle><date>2015-11-28</date><risdate>2015</risdate><volume>29</volume><issue>18</issue><spage>2409</spage><epage>2418</epage><pages>2409-2418</pages><issn>0269-9370</issn><eissn>1473-5571</eissn><abstract>OBJECTIVE:HIV-1 infection is characterized by altered intestinal barrier, gut microbiota dysbiosis, and systemic inflammation. We hypothesized that changes of the gut microbiota predict immune dysfunction and HIV-1 progression, and that antiretroviral therapy (ART) partially restores the microbiota composition. DESIGN:An observational study including 28 viremic patients, three elite controllers, and nine uninfected controls. Blood and stool samples were collected at baseline and for 19 individuals at follow-up (median 10 months) during ART. METHODS:Microbiota composition was determined by 16S rRNA sequencing (Illumina MiSeq). Soluble markers of microbial translocation and monocyte activation were analyzed by Limulus Amebocyte Lysate assay or ELISA. RESULTS:Several alpha-diversity measures, including number of observed bacterial species and Shannon index, were significantly lower in viremic patients compared to controls. The alpha diversity correlated with CD4 T-cell counts and inversely with markers of microbial translocation and monocyte activation. In multivariate linear regression, for every age and sex-adjusted increase in the number of bacterial species, the CD4 T-cell count increased with 0.88 (95% confidence interval 0.35–1.41) cells/μl (P = 0.002). After introduction of ART, microbiota alterations persisted with further reduction in alpha diversity. The microbiota composition at the genus level was profoundly altered in viremic patients, both at baseline and after ART, with Prevotella reduced during ART (P &lt; 0.007). CONCLUSIONS:Gut microbiota alterations are closely associated with immune dysfunction in HIV-1 patients, and these changes persist during short-term ART. Our data implicate that re-shaping the microbiota may be an adjuvant therapy in patients commencing successful ART.</abstract><cop>England</cop><pub>Copyright Wolters Kluwer Health, Inc</pub><pmid>26355675</pmid><doi>10.1097/QAD.0000000000000869</doi><tpages>10</tpages></addata></record>
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source MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Journals@Ovid Complete
subjects Adult
Aged
AIDS/HIV
Bacterial Translocation
Cohort Studies
DNA, Bacterial - chemistry
DNA, Bacterial - genetics
DNA, Ribosomal - chemistry
DNA, Ribosomal - genetics
Dysbiosis
Enzyme-Linked Immunosorbent Assay
Female
Gastrointestinal Microbiome
HIV Infections - immunology
HIV Infections - virology
HIV-1 - isolation & purification
Human immunodeficiency virus 1
Humans
Lentivirus
Limulus Test
Male
Microbiota
Middle Aged
Molecular Sequence Data
Prevotella
RNA, Ribosomal, 16S - genetics
Sequence Analysis, DNA
Young Adult
title Gut microbiota diversity predicts immune status in HIV-1 infection
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