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

作者：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

来源：PLoS Pathogens, 2014, 10(2): e1003829.

DOI：10.1371/journal.ppat.1003829

• HUMAN-IMMUNODEFICIENCY-VIRUS
• TO-CHILD TRANSMISSION
• BACTERIAL DIVERSITY
• RALSTONIA-PICKETTII
• VAGINAL MICROBIOTA
• PLASMA-LEVELS
• TRANSLOCATION
• HEALTH
• WOMEN
• IDENTIFICATION

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. @@@ Author Summary 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.

• 出版日期2014-2