Dissertation
Determining the impact of the microbiome on health and disease: usingstandard and advanced bioinformatics
University of Iowa
Doctor of Philosophy (PhD), University of Iowa
Autumn 2024
DOI: 10.25820/etd.007593
Abstract
The microbiome consists of all of the microorganisms found in and on our bodies. Advancements in sequencing technologies in the last two decades have identified the microbiome as a key player in maintaining our health, or homeostasis. The microbiome helps with several physiological processes including food digestion, immune system regulation, and pathogen defense. However, when the microbiome is in a perturbed or a “dysbiotic” state, homeostasis is lost, and this often predisposes and/or propagates disease. The presence of dysbiosis in diseases such as cancers and autoimmune disorders, highlights the importance of the microbiome in overall human health.
In the introduction of this thesis, I discuss prior studies on the microbiome, bioinformatic analysis, and the knowledge gaps in the field. The following chapters discuss our published work on dysbiosis in patients with breast cancer and multiple sclerosis as well as factors influencing the microbiome, such as dietary intervention. Additionally, I present a novel bioinformatics tool that utilizes unsupervised machine learning to address limitations in microbiome analysis.
Finally, I discuss our unpublished recent work, an investigation of both the oral microbiome and metabolome compositions in people with MS (pwMS). There is substantial evidence that the gut microbiome influences MS pathobiology, however there is limited data on the role of the oral microbiome (the second most diverse microbiome community) in MS. Additionally, the salivary metabolome is altered in patients with other neurological diseases but has not been studied in pwMS. Therefore, I performed studies to address these knowledge gaps and identified an oral microbiome and metabolome signature unique to pwMS. My results provide potential biomarkers for MS diagnostics, new targets for individualized therapies, and evidence that the oral microbiome is pivotal in understanding the pathobiology of MS.
Details
- Title: Subtitle
- Determining the impact of the microbiome on health and disease: usingstandard and advanced bioinformatics
- Creators
- Rachel L Fitzjerrells
- Contributors
- Ashutosh K Mangalam (Advisor)Sukirth M Ganesan (Committee Member)Grant D Brown (Committee Member)Jeffrey A Banas (Committee Member)Albert J Erives (Committee Member)
- Resource Type
- Dissertation
- Degree Awarded
- Doctor of Philosophy (PhD), University of Iowa
- Degree in
- Informatics (Bioinformatics and Computational Biology)
- Date degree season
- Autumn 2024
- DOI
- 10.25820/etd.007593
- Publisher
- University of Iowa
- Number of pages
- xvi, 200 pages
- Copyright
- Copyright 2024 Rachel L Fitzjerrells
- Language
- English
- Date submitted
- 11/13/2024
- Description illustrations
- illustrations, tables, graphs
- Description bibliographic
- Includes bibliographical references (pages 150-170).
- Public Abstract (ETD)
- The microbiome is all of the microorganisms (bacteria, viruses, parasites, etc.) that live in and on our bodies. These microbes help us digest food and improve our immune system. However, when the microbiome is in an irregular state, or “dysbiosis”, it can become harmful to our health. In fact, dysbiosis often accompanies disease. Several diseases are discussed in my thesis with chapters focusing on breast cancer and multiple sclerosis. Additionally, I present a new way to analyze the microbiome and then reveal how it could be used to predict treatment effectiveness based on the microbiome. One of the ways the microbiome impacts our health is through its production of small chemicals, or metabolites, which can influence normal functioning of our bodies. Thus, another chapter discusses how metabolites in the blood are altered after dietary supplementation. The final chapter presents the latest work, an investigation of both the oral microbiome and metabolome compositions in people with multiple sclerosis (pwMS). Many prior studies have found dysbiosis in the gut of pwMS, but few studies have looked at the oral microbiome. Additionally, in patients with other neurological diseases, their oral metabolites tend to be altered, however no study on the oral metabolites of pwMS has been undertaken. I ultimately found alterations in both the oral microbiome and metabolome of pwMS compared to healthy individuals. These findings provide us with new targets for personalized therapies, unique patterns for better diagnosis, and evidence that the oral microbiome is pivotal in understanding MS.
- Academic Unit
- IDGP in Informatics
- Record Identifier
- 9984774457502771
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