Heinrich, Victoria Ann
(2023)
Developing the Microbiome-Metabolome as a Targeted Therapy for Obesity-Associated Asthma.
Doctoral Dissertation, University of Pittsburgh.
(Unpublished)
Abstract
More than 25 million people in the United States are living with asthma, and more than one-third of adults with asthma are also obese. Obesity elevates the risk of hospitalization and worsens asthma severity. Obese adults with asthma comprise more than 60% of adult patients with severe asthma. This clinical phenotype of late-onset, obesity-associated asthma is especially challenging to treat and has a lower likelihood of asthma remission. Changes to the gut microbiome are associated with increased risk of asthma development, and obesity is known to disrupt the healthy gut microbiome and potentiate gut dysbiosis. Lung function in obesity-associated asthma is connected to dysregulated microbial metabolism in the gut. Past research studies demonstrate that an obesogenic gut microbiome worsens airway hyperresponsiveness in asthma. This dissertation research identifies targets of obesity-associated asthma linked to the microbiome-metabolome. We hypothesized that the gut microbiome-metabolome could be modified to improve lung function in obesity-associated asthma. The first chapter introduces the challenges of treating obesity-associated asthma, contributions of the gut microbiome to obesity-associated asthma, and the therapeutic potential of immunomodulator nitro-oleic acid as a host- and microbial-targeted intervention. In Chapter 2.0, we profile the gut-lung axis in a murine model of obese allergic asthma and decipher the interplay of the gut microbiota, metabolism, and host inflammation using multi-omics analyses. The third chapter builds upon the foundational work presented in Chapter 2.0 and examines the therapeutic benefit of orally administering a microbial-derived metabolite in obese allergic asthma. Finally, in the fourth chapter, we test nitro-oleic acid treatment in a murine model of lean allergic asthma and consider the potential overlap between potential mechanisms of lean and obese allergic asthma.
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Details
| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
|
| ETD Committee: |
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| Date: |
17 November 2023 |
| Date Type: |
Publication |
| Defense Date: |
27 June 2023 |
| Approval Date: |
17 November 2023 |
| Submission Date: |
19 July 2023 |
| Access Restriction: |
1 year -- Restrict access to University of Pittsburgh for a period of 1 year. |
| Number of Pages: |
198 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
School of Medicine > Molecular Pharmacology |
| Degree: |
PhD - Doctor of Philosophy |
| Thesis Type: |
Doctoral Dissertation |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
microbiome, obesity, asthma, metabolomics, metabolome |
| Date Deposited: |
17 Nov 2023 19:19 |
| Last Modified: |
17 Nov 2023 19:19 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/45117 |
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