Comparison of oral microbiota in patients with medication-related osteonecrosis of the jaw through oral microbiome analysis

다국어 초록 (Multilingual Abstract)

ABSTRACT

Comparison of oral microbiota in patients with medication-related osteonecrosis of the jaw through
oral microbiome analysis

Heon-Young Kim

Department of Dentistry
The Graduate School, Yonsei University

(Directed by Professor Young-Soo Jung)


Medication-related osteonecrosis of the jaw (MRONJ), which occurs due to drugs like antiresorptive agents, was first introduced in 2003 and is one of the most severe complications reported over the past 20 years. The prevalence of MRONJ has increased due to an increase in the number of patients receiving oral or intravenous bisphosphonates, receptor activator of nuclear factors κB ligand inhibitors, or drugs with antiangiogenic effects. However, the etiology of MRONJ has not been fully understood. No disease-causing markers have been identified, and a single model that explains the macroscopic and microscopic morphological changes in MRONJ has not been possible. Recently, oral bacteria have been suggested to play an important role in the pathogenesis of MRONJ. The purpose of this study was to identify the oral microbiome in MRONJ.
Fifteen patients who had confirmed MRONJ and visited the Department of Oral and Maxillofacial Surgery at Yonsei University Dental Hospital between 2021 and 2022 were recruited for this experiment. Samples from the affected and non-affected sides of patients diagnosed with MRONJ were collected. The composition and enumeration of the microbial community were analyzed, and diversity was compared to verity the ecological changes in groups using a next-generation sequencing-based 16S metagenomic analysis. The following results were obtained.

1. Although there was no significant difference in bacterial types between the non-affected and affected areas, we observed variations in the composition and coefficient in the microbiome analysis, which was performed at the phylum, genus, and species levels.
2. The identified microorganisms included many species known to cause periodontitis, gingival disease, and root canal infections. It can be inferred that MRONJ may occur due to various factors rather than being solely attributed to specific microorganisms. Understanding the interactions and functional aspects among these microorganisms may contribute to our comprehending of the etiology of MRONJ.
3. Addressing these limitations through larger-scale studies will further clarify the importance of oral bacteria in the pathogenesis of MRONJ and facilitate the development of effective therapeutic interventions for patients with MRONJ.

목차 (Table of Contents)

• TABLE OF CONTENTS
• LIST OF FIGURES ………………………………………………………………… ii
• ABSTRACT ………………………………………………………………………… iii
• I. INTRODUCTION ………………………………………………………………… 1
• II. MATERIALS & METHODS …………………………………………………… 5
• Study participant ……………………………………………………………........... 5
• Data collection ……………………………………………………………................ 5
• Sample preparation …………………………………………………………........... 9
• Polymerase chain reaction amplification and sequencing …...…………………..10
• Microbiome sequencing analysis and statistical analysis ………………………..11
• III. RESULTS ………………………………………………………………………..14
• Participant characteristics………………………………………………………….14
• Microbial community diversity analysis ……………………………..…………...16
• Comparison and analysis of alpha diversity …………………………………….17
• Comparison and analysis of beta diversity …………………………………….. 19
• Differences in Bacterial phyla, genera and species between groups
• (microbial taxonomy) ………………………………………………………………20
• Oral microbiome analysis at the phylum level ………………………………….20
• Oral microbiome analysis at the genus level ...…………………………………..23
• Oral microbiome analysis at the species level ……………………………….......27
• IV. DISCUSSION ……………………………………………………………………32
• V. CONCLUSION …………………………………………………………………...41
• REFERENCES ………………………………………………………………………42
• ABSTRACT (in Korean) ……………………………………………………………55