Microbial flora in persons with HIV likely play an important role in various diseases, but the nature of the microbiome in the lungs of persons with HIV has not been studied. High-throughput, DNA sequencing technologies now allow examination of complex microbial communities including organisms that cannot be cultured. These techniques have potential to yield important information about events in the lung during HIV and its associated pulmonary disorders. Chronic obstructive pulmonary disease (COPD) is of particular interest in the current era of HIV infection. Pathogenesis of HIV-associated COPD is poorly understood, but one or more infections may upregulate expression of HIV in the lungs, amplify the pulmonary inflammatory response, and lead to release of proteases or pro-apoptotic factors. Data from our group suggest that low level infection with Pneumocystis is increased in HIV-F subjects and associated with anatomic emphysema. Other infections alone or in combination are likely to be important in disease pathogenesis. Application of metagenomic techniques will allow us to determine patterns and changes in the population of microbes that play a key role in the pathogenesis and progression of emphysema in this population. The overall goals of this proposal are to determine the respiratory microbial flora (or microbiota) in HIV-I- and HIV- subjects and to establish its role in pathogenesis and progression of HIV-associated COPD using our ongoing cohorts.
Specific aims of the proposal are: 1. To compare the microbial community structure in the respiratory tract in subjects with and without HIV infection. 2. To test the hypothesis that the respiratory microbiome in HIV-I- subjects with COPD differs from that in HIV-f subjects without COPD and is related to COPD progression. 3. To test the hypothesis that bacterial products in the blood are detectable in HIV-f subjects with COPD and are associated with immune activation. We will perform oral wash, sputum induction, bronchoscopy, and blood draws in HIV- and HIV-I- subjects and carry out high-throughput virus metagenomics and bacterial, fungal and protozoal 16S rDNA analyses for characterization of microbiome population diversity. Results will be used to determine which microbes are present, their relative proportions, their location, and their relationship to HIV and COPD.

Public Health Relevance

This proposal will help us determine which infections are present In the lungs of people with HIV and how the infections might explain why HIV-infected individuals develop emphysema faster than non-HIV-infected people. This information will help us understand and treat emphysema in these patients and in the many non-HIV-infected people who suffer from emphysema.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01HL098962-05
Application #
8521354
Study Section
Special Emphasis Panel (ZHL1-CSR-Z (S1))
Program Officer
Colombini-Hatch, Sandra
Project Start
2009-09-23
Project End
2014-07-31
Budget Start
2013-08-01
Budget End
2014-07-31
Support Year
5
Fiscal Year
2013
Total Cost
$680,171
Indirect Cost
$162,764
Name
University of Pittsburgh
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Kitsios, Georgios D; Fitch, Adam; Manatakis, Dimitris V et al. (2018) Respiratory Microbiome Profiling for Etiologic Diagnosis of Pneumonia in Mechanically Ventilated Patients. Front Microbiol 9:1413
Tipton, Laura; Cuenco, Karen T; Huang, Laurence et al. (2018) Measuring associations between the microbiota and repeated measures of continuous clinical variables using a lasso-penalized generalized linear mixed model. BioData Min 11:12
Tipton, Laura; Müller, Christian L; Kurtz, Zachary D et al. (2018) Fungi stabilize connectivity in the lung and skin microbial ecosystems. Microbiome 6:12
Kitsios, Georgios D; Morowitz, Michael J; Dickson, Robert P et al. (2017) Dysbiosis in the intensive care unit: Microbiome science coming to the bedside. J Crit Care 38:84-91
Qin, Shulin; Clausen, Emily; Lucht, Lorrie et al. (2016) Presence of Tropheryma whipplei in Different Body Sites in a Cohort of Healthy Subjects. Am J Respir Crit Care Med 194:243-5
Segal, Leopoldo N; Clemente, Jose C; Tsay, Jun-Chieh J et al. (2016) Enrichment of the lung microbiome with oral taxa is associated with lung inflammation of a Th17 phenotype. Nat Microbiol 1:16031
Cribbs, Sushma K; Uppal, Karan; Li, Shuzhao et al. (2016) Correlation of the lung microbiota with metabolic profiles in bronchoalveolar lavage fluid in HIV infection. Microbiome 4:3
Morris, Alison; Paulson, Joseph N; Talukder, Hisham et al. (2016) Longitudinal analysis of the lung microbiota of cynomolgous macaques during long-term SHIV infection. Microbiome 4:38
Beck, James M; Schloss, Patrick D; Venkataraman, Arvind et al. (2015) Multicenter Comparison of Lung and Oral Microbiomes of HIV-infected and HIV-uninfected Individuals. Am J Respir Crit Care Med 192:1335-44
Cui, Lijia; Lucht, Lorrie; Tipton, Laura et al. (2015) Topographic diversity of the respiratory tract mycobiome and alteration in HIV and lung disease. Am J Respir Crit Care Med 191:932-42

Showing the most recent 10 out of 18 publications