Dr. Masae Kuboniwa, Associate Professor, Department of Preventive Dentistry, Graduate School of Dentistry

"Improving QOL through oral disease prevention and identifying risk indicators in saliva"

Dr. Masae Kuboniwa has been specializing in the prevention of periodontal diseases for almost 30 years. Periodontal disease has been found to cause a variety of disorders, thus preventive dentistry is crucial for improving people’s QOL (quality of life) and extending their healthy life expectancy. Dedicating herself to both clinical practices and basic research, she pursues breakthroughs in the understanding of the mechanisms behind how beneficial bacteria support periodontal disease bacteria (Porphyromonas gingivalis) by utilizing omics technologies in collaboration with researchers all across Osaka University.

Currently working to develop a non-invasive predictive tool using saliva for diagnosis and disease follow-up

Oral structure is quite complicated, with over 700 types of bacteria and disorders of bacteria flora leading to various diseases, thus a good balance of bacteria flora for oral health has yet to been discovered. Dr. Kuboniwa has been leading research to elucidate the molecular mechanisms of periodontal biofilm formation by focusing on the multilayered physical and chemical communication systems among the constituent organisms. More specifically, she is focusing on the microbial food chain where a process called metabolic cross-feeding occurs within the oral microbiome, wherein bacteria secrete products – often as nutritional wastes – that are then consumed by other bacteria, thereby promoting the survival of those bacteria. In 2022, Dr. Kuboniwa’s group revealed the role of a microbe known as Fusabacterium nucleatum (F. nucleatum) in the development of gum disease (periodontitis) [1]. They found that F. nucleatum produces polyamines such as putrescine and cadaverine through metabolic cross-feeding with other commensal bacteria and that these polyamines then create favorable conditions that allow the periodontal pathogen P. gingivalis to grow and spread, thus promoting the development of periodontitis.

Fig. Schematic of the F. nucleatum-integrated trophic network in oral biofilms revealed by this study.
Credit: 2022 Akito Sakanaka et al., Fusobacterium nucleatum metabolically integrates commensals and pathogens in oral biofilms, mSystems

Applying omics technologies to analyze detailed characterization of metabolomic profiles associated with multiple oral and metabolic traits may provide better understanding of the mechanisms of oral and systemic conditions. In this regard, saliva is similar to a mirror, reflecting changes in oral and systemic health conditions. Dr. Kuboniwa’s group recently identified metabolites that increase in saliva due to the development of inflammation in periodontal tissues, as well as metabolites that can predict the onset of diabetes and atherosclerosis using lifestyle-related disease biomarkers in saliva [2]. This study was a result of a collaboration between the fields of medicine, dentistry, and engineering at the university. Medical physicians are aware that periodontal diseases are related to various other medical disorders; therefore, it would be ideal if dental checkups could be incorporated as a part of standard medical checkups. The ultimate goal of this collaborative study is to detect periodontal diseases and diabetes through both dental and medical checkups.

Her path to becoming an established researcher in oral disease prevention has had some twists and turns

Dr. Kuboniwa studied biology at Kyoto University’s Faculty of Agriculture. Although she intended to proceed to graduate school, she changed her career after graduation to work in a company in a position unrelated to research in biology, as she was married and had a child during her undergraduate studies. At that time, the working environment for those who were raising children was not sufficiently arranged.

However, her passion for research never ceased. She carefully considered fields where her background could be relevant while also giving her the ability to look after her children without relocating her workplace. She ended up selecting dentistry to pursue research on bacteria found in the mouth, a stark contrast to the ‘plants’ she specialized in during her undergraduate studies in agriculture, yet focused on ‘flora’ all the same.

Dr. Kuboniwa is an inquisitive person, which led to her joining a clinical laboratory where she could engage in both clinical practice and research. Her genuine talent and passion towards research endowed her with the help of many people. She had the opportunity to conduct experiments on bacteria while also studying molecular biology, and spent two years as a postdoctoral fellow at the University of Florida where she achieved outstanding research results on an interaction between bacteria using a novel technique to examine it. This study led to a publication in Nature Microbiology.

What would a "future society where life shines brightly" look like for you?

“I would like to incorporate saliva testing into medical checkups so that early detection can be achieved without any burden to the body. Like healthy people regularly go to haircut, I wish they also go to preventive dentistry to test their saliva for periodontitis and other systemic conditions.”

Reference:
[1] Sakanaka, A., et al. (2022). Fusobacterium nucleatum Metabolically Integrates Commensals and Pathogens in Oral Biofilms. mSystems, 7(4), e00170-22. doi: 10.1128/msystems.00170-22
Also see:
ResOU: Microbial food chain: Nutritional interactions promoting periodontitis
https://resou.osaka-u.ac.jp/en/research/2022/20220901_4

[2] Sakanaka, A., et al. (2022). Salivary metabolic signatures of carotid atherosclerosis in patients with type 2 diabetes hospitalized for treatment.
Frontiers in Molecular Biosciences, 9, 1074282. doi: 10.3389/fmolb.2022.1074285

For more information:
Researchmap: https://researchmap.jp/MasaeKuboniwa_URL?lang=en
Department of Preventive Dentistry, Graduate School of Dentistry: https://global.dent.osaka-u.ac.jp/prevent/preventive-dentistry-department-of-preventive-dentist

Text: Saori Obayashi/Edit: Christopher Bubb