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Determining the variability in the lung microbiome throughout the course of mycobacterium tuberculosis infection

Bryant, MacKenzie (2017) Determining the variability in the lung microbiome throughout the course of mycobacterium tuberculosis infection. Master's Thesis, University of Pittsburgh. (Unpublished)

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Abstract

Tuberculosis remains a major health threat throughout the world, despite having a vaccine and treatments. Mycobacterium tuberculosis (Mtb) infects alveolar macrophages in the lung and inflammation occurs after infection. The lung microbiome in regards to Mtb infection is poorly understood, and whether inflammation from infection affects the lung microbiome is unknown. The goal of our study is to determine whether Mtb induces a significant and durable change in the lung microbiome of cynomolgus macaques. We investigated and compared the community clusters between the lung and oral cavity, assessed how the diversity of the lung microbiota changes throughout infection, and associated these changes in the lung with inflammation. Bronchoalveolar lavage (BAL) was obtained pre-infection and at several time points post-Mtb infection, as well as oral wash and saline bronchoscope control samples from respective macaques. Operational taxonomic units (OTUs) were generated after 16s rRNA sequencing was performed once DNA was extracted from collected samples. We profiled microbial communities to see the community structure differences between oral and lung environment and show how the microbiome changes throughout infection. PET/CT imaging was used to visualize and quantify inflammation over the course of infection by using FDG avidity (total PET HOT). Our results show that the oral and lung compartments are distinct with regard to community structure, distinct bacterial taxa are more relatively abundant in certain lobes, and lung inflammation and lung microbiome changes are variable within macaques and between macaques. Analysis of the first cohort of macaques (N=10) did not reveal correlations between lung inflammation and relative abundance or alpha-diversity, but our data is preliminary and based on small sample size. Our sample size will greatly increase after the second cohort of macaques are fully sequenced and analyzed. These changes and disruptions in the lung microbiome may have public health relevance in regards to overall lung health and may also play a role in the outcome of Mtb infection.


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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Bryant, MacKenziemmb138@pitt.edummb138
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Thesis AdvisorFlynn, JoAnne Ljoanne@pitt.edu
Committee MemberMattila, Joshua Tjmattila@pitt.edu
Committee MemberMailliard, Robbie Brbm19@pitt.edu
Date: 29 June 2017
Date Type: Publication
Defense Date: 11 April 2017
Approval Date: 29 June 2017
Submission Date: 27 March 2017
Access Restriction: 2 year -- Restrict access to University of Pittsburgh for a period of 2 years.
Number of Pages: 71
Institution: University of Pittsburgh
Schools and Programs: Graduate School of Public Health > Infectious Diseases and Microbiology
Degree: MS - Master of Science
Thesis Type: Master's Thesis
Refereed: Yes
Uncontrolled Keywords: tuberuclosis microbiome inflammation
Date Deposited: 29 Jun 2017 23:10
Last Modified: 01 May 2019 05:15
URI: http://d-scholarship.pitt.edu/id/eprint/31052

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