A Compositional Look at the Human Gastrointestinal Microbiome and Immune Activation Parameters in HIV Infected Subjects

HIV progression is characterized by immune activation and microbial translocation. One factor that may be contributing to HIV progression could be a dysbiotic microbiome. We therefore hypothesized that the GI mucosal microbiome is altered in HIV patients and this alteration correlates with immune ac...

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Published in:	PLoS pathogens Vol. 10; no. 2; p. e1003829
Main Authors:	Mutlu, Ece A., Keshavarzian, Ali, Losurdo, John, Swanson, Garth, Siewe, Basile, Forsyth, Christopher, French, Audrey, DeMarais, Patricia, Sun, Yan, Koenig, Lars, Cox, Stephen, Engen, Phillip, Chakradeo, Prachi, Abbasi, Rawan, Gorenz, Annika, Burns, Charles, Landay, Alan
Format:	Journal Article
Language:	English
Published:	United States Public Library of Science 01.02.2014 Public Library of Science (PLoS)
Subjects:	Antiretroviral drugs Bacteria Development and progression Disease Female Gastrointestinal system High-Throughput Nucleotide Sequencing Highly active antiretroviral therapy HIV HIV (Viruses) HIV infection HIV Infections - immunology HIV Infections - microbiology Human immunodeficiency virus Humans Illnesses Immune system Intestinal Mucosa - immunology Intestinal Mucosa - microbiology Lymphocytes Male Medical research Medicine Medicine, Experimental Microbiota Microbiota (Symbiotic organisms) Middle Aged Mortality Physiological aspects Reverse Transcriptase Polymerase Chain Reaction RNA, Ribosomal, 16S - analysis HIV Infections Intestinal Mucosa Microbiota Humans Middle Aged Female Male High-Throughput Nucleotide Sequencing RNA, Ribosomal, 16S Reverse Transcriptase Polymerase Chain Reaction
ISSN:	1553-7374, 1553-7366, 1553-7374
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Abstract	HIV progression is characterized by immune activation and microbial translocation. One factor that may be contributing to HIV progression could be a dysbiotic microbiome. We therefore hypothesized that the GI mucosal microbiome is altered in HIV patients and this alteration correlates with immune activation in HIV. 121 specimens were collected from 21 HIV positive and 22 control human subjects during colonoscopy. The composition of the lower gastrointestinal tract mucosal and luminal bacterial microbiome was characterized using 16S rDNA pyrosequencing and was correlated to clinical parameters as well as immune activation and circulating bacterial products in HIV patients on ART. The composition of the HIV microbiome was significantly different than that of controls; it was less diverse in the right colon and terminal ileum, and was characterized by loss of bacterial taxa that are typically considered commensals. In HIV samples, there was a gain of some pathogenic bacterial taxa. This is the first report characterizing the terminal ileal and colonic mucosal microbiome in HIV patients with next generation sequencing. Limitations include use of HIV-infected subjects on HAART therapy.
AbstractList	HIV progression is characterized by immune activation and microbial translocation. One factor that may be contributing to HIV progression could be a dysbiotic microbiome. We therefore hypothesized that the GI mucosal microbiome is altered in HIV patients and this alteration correlates with immune activation in HIV. 121 specimens were collected from 21 HIV positive and 22 control human subjects during colonoscopy. The composition of the lower gastrointestinal tract mucosal and luminal bacterial microbiome was characterized using 16S rDNA pyrosequencing and was correlated to clinical parameters as well as immune activation and circulating bacterial products in HIV patients on ART. The composition of the HIV microbiome was significantly different than that of controls; it was less diverse in the right colon and terminal ileum, and was characterized by loss of bacterial taxa that are typically considered commensals. In HIV samples, there was a gain of some pathogenic bacterial taxa. This is the first report characterizing the terminal ileal and colonic mucosal microbiome in HIV patients with next generation sequencing. Limitations include use of HIV-infected subjects on HAART therapy. HIV progression is characterized by immune activation and microbial translocation. One factor that may be contributing to HIV progression could be a dysbiotic microbiome. We therefore hypothesized that the GI mucosal microbiome is altered in HIV patients and this alteration correlates with immune activation in HIV. 121 specimens were collected from 21 HIV positive and 22 control human subjects during colonoscopy. The composition of the lower gastrointestinal tract mucosal and luminal bacterial microbiome was characterized using 16S rDNA pyrosequencing and was correlated to clinical parameters as well as immune activation and circulating bacterial products in HIV patients on ART. The composition of the HIV microbiome was significantly different than that of controls; it was less diverse in the right colon and terminal ileum, and was characterized by loss of bacterial taxa that are typically considered commensals. In HIV samples, there was a gain of some pathogenic bacterial taxa. This is the first report characterizing the terminal ileal and colonic mucosal microbiome in HIV patients with next generation sequencing. Limitations include use of HIV-infected subjects on HAART therapy.HIV progression is characterized by immune activation and microbial translocation. One factor that may be contributing to HIV progression could be a dysbiotic microbiome. We therefore hypothesized that the GI mucosal microbiome is altered in HIV patients and this alteration correlates with immune activation in HIV. 121 specimens were collected from 21 HIV positive and 22 control human subjects during colonoscopy. The composition of the lower gastrointestinal tract mucosal and luminal bacterial microbiome was characterized using 16S rDNA pyrosequencing and was correlated to clinical parameters as well as immune activation and circulating bacterial products in HIV patients on ART. The composition of the HIV microbiome was significantly different than that of controls; it was less diverse in the right colon and terminal ileum, and was characterized by loss of bacterial taxa that are typically considered commensals. In HIV samples, there was a gain of some pathogenic bacterial taxa. This is the first report characterizing the terminal ileal and colonic mucosal microbiome in HIV patients with next generation sequencing. Limitations include use of HIV-infected subjects on HAART therapy. HIV progression is characterized by immune activation and microbial translocation. One factor that may be contributing to HIV progression could be a dysbiotic microbiome. We therefore hypothesized that the GI mucosal microbiome is altered in HIV patients and this alteration correlates with immune activation in HIV. 121 specimens were collected from 21 HIV positive and 22 control human subjects during colonoscopy. The composition of the lower gastrointestinal tract mucosal and luminal bacterial microbiome was characterized using 16S rDNA pyrosequencing and was correlated to clinical parameters as well as immune activation and circulating bacterial products in HIV patients on ART. The composition of the HIV microbiome was significantly different than that of controls; it was less diverse in the right colon and terminal ileum, and was characterized by loss of bacterial taxa that are typically considered commensals. In HIV samples, there was a gain of some pathogenic bacterial taxa. This is the first report characterizing the terminal ileal and colonic mucosal microbiome in HIV patients with next generation sequencing. Limitations include use of HIV-infected subjects on HAART therapy. Human immunodeficiency virus (HIV) infection related illness progresses despite the control of the virus itself by medications that stop the replication of the virus. This happens because the immune system gets activated. While the causes for such activation of the immune system are not exactly known, immune activation in HIV infection may be occurring as a result of bacteria or their products in the digestive tract. This study looks at the types of bacteria that reside in the lower intestinal tract in patients infected with human immunodeficiency virus, using state of the art sequencing technology, that can simultaneously look at thousands of bacteria. We have found that the bacteria at the end of the small bowel (an area also called the terminal ileum), at the right and left sides of the large intestine and in the stool is different in patients infected with the human immunodeficiency virus. HIV patients harbor more bacteria that have been linked to other human diseases and have been previously described as harmful. This finding is new and could open up a new frontier of study that could now pave the way to gain a deeper understanding of how the HIV causes illness. HIV progression is characterized by immune activation and microbial translocation. One factor that may be contributing to HIV progression could be a dysbiotic microbiome. We therefore hypothesized that the GI mucosal microbiome is altered in HIV patients and this alteration correlates with immune activation in HIV. 121 specimens were collected from 21 HIV positive and 22 control human subjects during colonoscopy. The composition of the lower gastrointestinal tract mucosal and luminal bacterial microbiome was characterized using 16S rDNA pyrosequencing and was correlated to clinical parameters as well as immune activation and circulating bacterial products in HIV patients on ART. The composition of the HIV microbiome was significantly different than that of controls; it was less diverse in the right colon and terminal ileum, and was characterized by loss of bacterial taxa that are typically considered commensals. In HIV samples, there was a gain of some pathogenic bacterial taxa. This is the first report characterizing the terminal ileal and colonic mucosal microbiome in HIV patients with next generation sequencing. Limitations include use of HIV-infected subjects on HAART therapy.
Audience	Academic
Author	Losurdo, John Siewe, Basile Swanson, Garth Gorenz, Annika Landay, Alan Forsyth, Christopher Sun, Yan Chakradeo, Prachi Burns, Charles Abbasi, Rawan French, Audrey Mutlu, Ece A. DeMarais, Patricia Engen, Phillip Koenig, Lars Keshavarzian, Ali Cox, Stephen
AuthorAffiliation	1 Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, Rush University Medical Center, Chicago, Illinois, United States of America 3 Department of Physiology and Molecular Biophysics, Rush University Medical Center, Chicago, Illinois, United States of America Stanford University, United States of America 2 Department of Pharmacology, The Graduate College, Rush University, Chicago, Illinois, United States of America 6 Department of Biochemistry, The Graduate College, Rush University, Chicago, Illinois, United States of America 7 Ruth M. Rothstein CORE Center/Department of Medicine, Rush University Medical Center, Chicago, Illinois, United States of America 8 Research and Testing Laboratory, LLC., Lubbock, Texas, United States of America 4 Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, The Netherlands 5 Department of Immunology/Microbiology, Rush University Medical Center, Chicago, Illinois, Uni
AuthorAffiliation_xml	– name: 3 Department of Physiology and Molecular Biophysics, Rush University Medical Center, Chicago, Illinois, United States of America – name: 6 Department of Biochemistry, The Graduate College, Rush University, Chicago, Illinois, United States of America – name: 8 Research and Testing Laboratory, LLC., Lubbock, Texas, United States of America – name: Stanford University, United States of America – name: 2 Department of Pharmacology, The Graduate College, Rush University, Chicago, Illinois, United States of America – name: 7 Ruth M. Rothstein CORE Center/Department of Medicine, Rush University Medical Center, Chicago, Illinois, United States of America – name: 4 Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, The Netherlands – name: 5 Department of Immunology/Microbiology, Rush University Medical Center, Chicago, Illinois, United States of America – name: 1 Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, Rush University Medical Center, Chicago, Illinois, United States of America – name: 9 Rush Medical College, Armour Academic Center, Chicago, Illinois, United States of America
Author_xml	– sequence: 1 givenname: Ece A. surname: Mutlu fullname: Mutlu, Ece A. – sequence: 2 givenname: Ali surname: Keshavarzian fullname: Keshavarzian, Ali – sequence: 3 givenname: John surname: Losurdo fullname: Losurdo, John – sequence: 4 givenname: Garth surname: Swanson fullname: Swanson, Garth – sequence: 5 givenname: Basile surname: Siewe fullname: Siewe, Basile – sequence: 6 givenname: Christopher surname: Forsyth fullname: Forsyth, Christopher – sequence: 7 givenname: Audrey surname: French fullname: French, Audrey – sequence: 8 givenname: Patricia surname: DeMarais fullname: DeMarais, Patricia – sequence: 9 givenname: Yan surname: Sun fullname: Sun, Yan – sequence: 10 givenname: Lars surname: Koenig fullname: Koenig, Lars – sequence: 11 givenname: Stephen surname: Cox fullname: Cox, Stephen – sequence: 12 givenname: Phillip surname: Engen fullname: Engen, Phillip – sequence: 13 givenname: Prachi surname: Chakradeo fullname: Chakradeo, Prachi – sequence: 14 givenname: Rawan surname: Abbasi fullname: Abbasi, Rawan – sequence: 15 givenname: Annika surname: Gorenz fullname: Gorenz, Annika – sequence: 16 givenname: Charles surname: Burns fullname: Burns, Charles – sequence: 17 givenname: Alan surname: Landay fullname: Landay, Alan
BackLink	https://www.ncbi.nlm.nih.gov/pubmed/24586144$$D View this record in MEDLINE/PubMed
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Copyright	COPYRIGHT 2014 Public Library of Science 2014 Mutlu et al 2014 Mutlu et al 2014 Mutlu et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Mutlu EA, Keshavarzian A, Losurdo J, Swanson G, Siewe B, et al. (2014) A Compositional Look at the Human Gastrointestinal Microbiome and Immune Activation Parameters in HIV Infected Subjects. PLoS Pathog 10(2): e1003829. doi:10.1371/journal.ppat.1003829
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Keywords	HIV Infections Intestinal Mucosa Microbiota Humans Middle Aged Female Male High-Throughput Nucleotide Sequencing RNA, Ribosomal, 16S Reverse Transcriptase Polymerase Chain Reaction
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Notes	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Conceived and designed the experiments: EAM AK JL GS BS CF AL. Performed the experiments: BS YS LK SC PE CB PC RA AG AF PD. Analyzed the data: EAM AK LK AF PD PE PC. Contributed reagents/materials/analysis tools: YS LK SC. Wrote the paper: EAM AK AL. Reviewed and/or edited the manuscript: EAM AK JL GS BS CF AL YS LK SC CB PE RA AG AF PD PC. The authors have declared that no competing interests exist.
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Snippet	HIV progression is characterized by immune activation and microbial translocation. One factor that may be contributing to HIV progression could be a dysbiotic... HIV progression is characterized by immune activation and microbial translocation. One factor that may be contributing to HIV progression could be a...
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SubjectTerms	Antiretroviral drugs Bacteria Development and progression Disease Female Gastrointestinal system High-Throughput Nucleotide Sequencing Highly active antiretroviral therapy HIV HIV (Viruses) HIV infection HIV Infections - immunology HIV Infections - microbiology Human immunodeficiency virus Humans Illnesses Immune system Intestinal Mucosa - immunology Intestinal Mucosa - microbiology Lymphocytes Male Medical research Medicine Medicine, Experimental Microbiota Microbiota (Symbiotic organisms) Middle Aged Mortality Physiological aspects Reverse Transcriptase Polymerase Chain Reaction RNA, Ribosomal, 16S - analysis
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Title	A Compositional Look at the Human Gastrointestinal Microbiome and Immune Activation Parameters in HIV Infected Subjects
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