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UBC Theses and Dissertations

An exploration of the lung microbiome and DNA methylation in patients infected with human immunodeficiency virus Xu, Yan


Background: With the advent of antiretroviral therapy, patients infected with human immunodeficiency virus (HIV) can achieve near normal life expectancies. However, the risk for chronic illnesses such as chronic obstructive pulmonary disease (COPD) remains higher in HIV-infected patients despite improved survival. In disease states such as COPD, the microenvironment of the lungs can change dramatically, which creates permissive niches that allow for selective growth and reproduction of microbes. These changes may influence or be influenced by epigenetic alterations, specifically the methylation and demethylation of sites along the genetic code. We hypothesize that the microbiome and methylation profiles in the lower airway of HIV-infected patients are different compared to those of uninfected patients. These changes may prove relevant to the progression of chronic lung complications. Experimental Approach: This thesis examined small airway epithelial cells collected from patients infected with HIV and from uninfected subjects. Data on bacterial microbiome were obtained by using touchdown polymerase chain reaction (PCR) on epithelial cell DNA followed by MiSeq sequencing of specific variable regions on the bacterial 16S rRNA gene. For methylation profiling, DNA samples from the same airway epithelial cells were bisulfite converted and sequenced with the Illumina Infinium 450K HumanMethylation platform. Microbial diversity calculations, and linear regression models of methylation data were analyzed on Vegan and Limma packages in R, respectively. Results: The bacterial microbiome from small airway epithelial cells within the lungs of HIV-infected patients was distinct from that in uninfected patients. These changes included decreased diversity and decreased richness. Moreover, certain operational taxonomic units (OTUs) were able to distinguish HIV from non-HIV samples. Furthermore, a significant difference in global methylation patterns was identified. Conclusion: The microbiome and methylation profiles from small airway epithelial cells in HIV-infected individuals are significantly different from those in uninfected individuals, which may in part explain the heightened susceptibility of HIV-infected patients to COPD.

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