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Oral microbiome and metabolome in fixed orthodontic therapy
Thesis   Open access

Oral microbiome and metabolome in fixed orthodontic therapy

Ronak J Bhagat
University of Iowa
Master of Science (MS), University of Iowa
Spring 2024
DOI: 10.25820/etd.007409
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Abstract

BACKGROUND With orthodontics gaining popularity for enhancing esthetics and function, approximately 4.5 million Americans, predominantly aged 6 to 18, wear braces. Yet, fixed orthodontic therapy (FOT) poses challenges to oral hygiene, leading to increased plaque, heightened risks of caries, gingivitis, periodontitis, and common complications such as gingival inflammation and elevated periodontal pathogens during orthodontic treatment. Furthermore, orthodontic tooth movement involves a complex tissue remodeling process which are all intricately linked with immune cells and immunologically active substances. We aim to comprehensively evaluate the oral microbiome, inflammatory mediators, and metabolites from subgingival plaque samples in patients undergoing FOT at various time points during treatment. METHODS 55 orthodontic patients and 14 periodontally healthy control subjects participated in this cross-sectional analysis. These patients ranged in age from 11-20 years and were matched for age, gender, and dentition. Subgingival plaque samples and GCF (Gingival Crevicular Fluid) were collected at 6 months, 12 months, or 24 months (about 2 years)/deband in orthodontic therapy. DNA isolation was performed using the Qigen DNEasy kit for plaque samples. 16S rRNA sequencing was performed with Illumina MiSeq platform. Analyses were conducted with DADA2, QIIME2. Taxonomy identification was determined against the HOMD (Human Oral Microbial Database) database. Alpha and beta-diversity were assessed. Metabolomic data was assessed via gas chromatography/mass spectrometry (GC/MS) analyses. A MILLIPLEX® Multiplex for Luminex® Immunoassay (Millipore, Sigma Aldrich) was used for cytokine and immune mediator analysis. RESULTS Patients undergoing FOT had a significantly distinct bacterial composition compared to controls. The microbiome of FOT was associated with an increase in several caries and inflammation associated species such as Saccharibacteria, Treponema, Prevotella, and Streptococcus species. Changes in the oral microbiome were most significant during earlier time points of treatment. Many of the metabolites identified in the study could be grouped into one of three categories: inflammation, collagen metabolism, and bone homeostasis, all of which are significant processes during orthodontic therapy. Analysis of the immune mediators revealed there were elevated levels of pro-inflammatory mediators like INF-y, IL-22, IL-1B, and IL-7 at 6 months while IL-10 was decreased throughout all time points in FOT. CONCLUSION Our integrated -omics approach is the first step towards understanding the comprehensive interdependent roles of oral microbiota, the host response, and metabolites associated in the subgingival environment of patients undergoing FOT.
Metabolites Fixed Orthodontics Oral Microbiome Orthodontic therapy Periodontal disease Subgingival Plaque

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