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Jeremy Bobera Thesis997.19 kB
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Thesis
Metabolomic profiling of oral niches in health and obesity
University of Iowa
Master of Science (MS), University of Iowa
Spring 2025
DOI: 10.25820/etd.007942
Abstract
BACKGROUND
Research is currently intensively studying the gut microbiome and immune network to its corresponding metabolome on possible links to health. Evidence suggests that the metabolome is crucial for not only local gut health but systemic health. However, when focusing on the oral cavity, we have almost no knowledge of its local metabolome. Preliminary studies have only investigated the oral metabolome in single site-specific areas. One specific aim of our project was to define the oral metabolome among various oral niches, specifically saliva, gingival crevicular fluid, and gingival tissue in the absence of disease. Our second aim was to then compare the oral metabolome in normal weight individuals to obese individuals to gain insight to changes that may occur to the metabolome. Emerging evidence suggests a bidirectional association between obesity and oral health, with individuals with obesity being twice as likely to develop periodontitis. However, the mechanisms underlying this link remain unclear. The oral mucosa, a key barrier site, involves complex host-microbe interactions, and disruptions in this balance can lead to periodontitis. Therefore, it is essential to identify the end-stage small molecules (metabolites) in this environment, and the host immune response to these molecules.
METHODS
Unstimulated saliva, subgingival plaque, and gingival tissue biopsies (subset of 11 patients) were collected from 40 periodontally healthy obese (OB), overweight (OW), and normal weight healthy (NWH) adults at the University of Iowa College of Dentistry. Subjects were frequency-matched for age, gender, and ethnicity. Gas Chromatography/Mass Spectrometry identified metabolites, which were annotated using the Small Molecule Pathway Database, with enrichment analysis determining significance. Multiplex assays quantified adipokines and cytokines, with statistical significance assessed using MAsLin2. Sparse Partial Least Squares Regression (sPLS) integrated metabolome and immune data. Differential expression of metabolites across normal weight, overweight, and obese individuals was utilized to compare statistical significance among metabolite abundances. Then Data Integration Analysis for Biomarker Discovery (DIABLO) was performed to uncover correlations between oral metabolites, immune system, and microbiome.
RESULTS
Niche-specific metabolome alterations were observed among saliva, gingival crevicular fluid and gingival tissue. Of note were Indolaldehyde, arachidate, tyrosine, mevalonate, glucose-6-phosphate, citrulline, malonate, tryptophan, and isocitrate. sPLS findings illustrated that obese individuals display distinct clustering when compared to overweight and normal weight individuals. Drivers for obesity’s distinct clustering were found to be metabolites associated with tryptophan – kynurenine, arachidonic acid, and inflammatory fatty acid metabolism. Statistically significant differences in oral metabolite abundances comparing Obesity to healthy weight included heptadecanoate, arachidate, kynurenine, laurate, methyl citrate, linoleate, aspartate, phosphoenolpyruvate, myristate, and tryptophan. DIABLO analysis demonstrated that these key oral metabolites were linked to pro-inflammatory cytokines and chemokines such as IL-1beta and IFNα2. In addition to microbial species, Lautropia mirabilis and Selenomonas sp. Which are associated with gingival health and periodontal disease respectively.
CONCLUSION
To our knowledge our study is the first to characterize the oral metabolome by using multiple oral niches such as saliva, gingival crevicular fluid and gingival tissue samples in healthy individuals. Comparisons were made among the different oral niches and distinct differences and similarities were observed among each location. Patients were further compared based on BMI status to determine if normal weight individuals differ from that of obese. Our findings discovered unique oral metabolomes and immune alterations in obese patients, even without clinical periodontal disease. Specific oral metabolites linked to pro-inflammatory pathways, including the tryptophan–kynurenine axis, the arachidonic acid pathway, and several inflammatory fatty acids were observed in the obese population. Further integrative analysis revealed that these obesity-associated metabolites were correlated with shifts in local immune cytokines and microbial species. These findings highlight the need for personalized treatment strategies for this population.
Details
- Title: Subtitle
- Metabolomic profiling of oral niches in health and obesity
- Creators
- Jeremy A. Bobera
- Contributors
- Sukirth Ganesan (Advisor)Liu Hong (Committee Member)Emily Lanzel (Committee Member)Shareef Dabdoub (Committee Member)
- Resource Type
- Thesis
- Degree Awarded
- Master of Science (MS), University of Iowa
- Degree in
- Oral Science
- Date degree season
- Spring 2025
- DOI
- 10.25820/etd.007942
- Publisher
- University of Iowa
- Number of pages
- xiii, 43 pages
- Copyright
- Copyright 2025 Jeremy A. Bobera
- Language
- English
- Date submitted
- 04/15/2025
- Description illustrations
- Illustrations, tables, graphs, charts
- Description bibliographic
- Includes bibliographical references (pages 38-43).
- Public Abstract (ETD)
Research on the oral cavity has traditionally focused on bacteria and the immune system. However, recent studies are beginning to explore the oral metabolome (the small molecules produced by these ecosystems). These initial studies have only focused on the small molecules in one specific area of the mouth.
Our study aimed to identify and compare metabolites across different regions of the mouth in healthy individuals. To achieve this, we collected saliva, gum tissue, and fluid that is found underneath the gums called the gingival crevicular fluid or (GCF). Once we identified the metabolites present in each area, we compared the similarities and differences. Once we identified the molecules located in healthy individuals' oral cavity, we compared them to overweight and obese individuals. Obesity is known to alter the metabolome of other organ systems such as the gut. We aimed to see if it can impact the oral metabolome as well.
Our findings are the first to define the metabolome in multiple regions of the oral cavity. We revealed that each individual area of the mouth contained distinct molecules when compared to one another. We also identified that obese patients exhibited different metabolites compared to healthy weight individuals. Some of these molecules that were found in obese individuals are known to be associated with other systemic illnesses or diseases.
- Academic Unit
- Oral Pathology, Radiology and Medicine; Craniofacial Anomalies Research Center
- Record Identifier
- 9984831125002771
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