Thesis
Salivary microbiome, metabolome and host immune changes in patients undergoing fixed orthodontic therapy
University of Iowa
Master of Science (MS), University of Iowa
Spring 2024
DOI: 10.25820/etd.007497
Abstract
BACKGROUND
Patients undergo fixed orthodontic treatment (FOT) to improve dental and facial aesthetics, correct occlusal function, and/or eliminate traumatic occlusion. However, many patients, especially teenagers, struggle to maintain good oral hygiene. This can result in plaque-related complications such as periodontal diseases, caries, and white spot lesions. Plaque-mediated diseases result from imbalances in the microbiome leading to an enrichment of disease associated pathogens in the microbial community and trigger host immune responses that can be destructive to tissues. Saliva samples can provide information about microbes, immune signatures, and metabolites present in the oral environment and are easy to collect during routine visits. We aimed to comprehensively characterize how the microbial composition, proinflammatory mediators, and metabolites of the salivary environment change throughout FOT.
METHODS
This cross-sectional study analyzed saliva samples from 55 orthodontic patients, aged 11-20 years, and 29 periodontally healthy control subjects not undergoing orthodontic treatment, matched for age, gender, and dentition. Unstimulated saliva samples were collected from patients at 6 months, 12 months, or 24 months into orthodontic treatment. DNA was isolated from saliva samples, quantified, and normalized. The V3-V4 regions of the 16S rRNA gene were amplified and sequencing was completed using the Illumina MiSeq platform to collect 300 base pair paired-end reads. Sequences were annotated against the SILVA database. Saliva samples were sent to the Metabolomics Core (FOEDRC) for metabolite extraction and derivatization and Gas Chromatography/Mass Spectrometry analysis. A MILLIPLEX® Multiplex for Luminex® Immunoassay (Millipore, Sigma Aldrich) was used to determine levels of multiple cytokines and immune mediators, including L-1β, IL-6, IL-8/CXCL8, IL-10, TNF-α, VEGF-A, TGF-β1, MIF, RANKL, M-CSF, and INF- γ, present in the saliva samples.
RESULTS
FOT was associated with a significant reduction in bacterial diversity compared to controls; however, the diversity was similar among different time points. With FOT, we saw an increase in many disease-associated species and a decrease in several health-associated and commensal species. Timepoint-specific shifts were observed in the salivary metabolome; metabolic biomarkers of caries and periodontal disease were most abundant at our earliest sample timepoints, 6 and 12 months. Salivary immune-biomarkers of caries and periodontitis, including TNF-α, IL-1β, IL-6, and IL-10 were elevated at later treatment timepoints.
CONCLUSION
Our cross-sectional study is a step towards comprehensively understanding how the salivary microbiome, metabolome, and host immune response change throughout FOT. The placement of fixed appliances induces dysbiosis in the salivary oral microbiome, which causes a shift in the salivary environment from health towards disease. Early disease intervention may be crucial for preventing negative sequalae of orthodontic treatment with fixed appliances. In the future, this foundation may aid in patient risk profiling and disease intervention during orthodontic treatment.
Details
- Title: Subtitle
- Salivary microbiome, metabolome and host immune changes in patients undergoing fixed orthodontic therapy
- Creators
- Madeleine L. Daily
- Contributors
- Sukirth Ganesan (Advisor)Lina M. Moreno Uribe (Committee Member)Michael A. Callan (Committee Member)Kyungsup Shin (Committee Member)Shareef Dabdoub (Committee Member)Shankar Rengasamy Venugopalan (Committee Member)
- Resource Type
- Thesis
- Degree Awarded
- Master of Science (MS), University of Iowa
- Degree in
- Orthodontics
- Date degree season
- Spring 2024
- DOI
- 10.25820/etd.007497
- Publisher
- University of Iowa
- Number of pages
- xi, 64 pages
- Copyright
- Copyright 2024 Madeleine L. Daily
- Language
- English
- Date submitted
- 04/17/2024
- Description illustrations
- Illustrations, tables, graphs, charts
- Description bibliographic
- Includes bibliographical references (pages 53-64).
- Public Abstract (ETD)
Patients commonly elect to have braces (fixed orthodontic appliances) to straighten their teeth or fix their bite. Often times, patients have a hard time keeping their teeth clean with braces on because there are many nooks and crannies for food and bacteria to stick to, forming “plaque”. We, as humans, normally have hundreds of bacteria living in our mouths. When our mouths are healthy, these bacteria live in harmony with our body’s immune system. When there is a change in the population of bacteria living in one’s mouth—which happens when there is a build-up of plaque around braces—disharmony ensues, and that person is more likely to get cavities and gum disease. This a problem for patients with braces, so the purpose of our study is to try to understand exactly how bacteria and our body’s immune system change when braces are on so that we might be able to target those particular bacteria in disease prevention.
We collected saliva from four groups of patients: patients without braces and patients who had braces on for 6, 12, and 24 months. In the laboratory, we performed tests to examine the bacteria, metabolites (small molecules released by bacteria), and our body’s immune response, and we compared differences between groups.
We found that patients with braces have a less diverse population of bacteria in their mouths than patients without braces. Patients with braces had more disease-associated bacteria and fewer health-associated bacteria. Early on in braces treatment, metabolites that are associated with cavities and gum disease were most abundant. Later in treatment we saw an increase in markers of inflammation associated with cavities and gum disease. We hope to use our findings, and the findings of future studies, to come up with treatments to prevent cavities and gum disease in patients with braces.
- Academic Unit
- Orthodontics; Craniofacial Anomalies Research Center
- Record Identifier
- 9984647454702771
Metrics
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