Microparticles Show Mysterious Connections whthin the Body

Ultrafine particles released by periodontal pathogens are signs that can be seen throughout the body.

Faculty's Column (Early-Career) November 27, 2025

OHKURA Naoto Senior Lecturer, Operative Dentistry and Endodontics, Niigata University Medical & Dental Hospital

Oral lesions are involved in some diseases in distant organs, and in recent years, the mechanisms underlying this association have gradually become clearer at the molecular level.

Periodontal disease is an inflammatory condition caused by periodontal pathogens in the gums and alveolar bone that support the teeth. It leads to the gradual destruction of teeth. It is a leading cause of tooth loss in adults and is increasingly recognized as having a significant impact on overall health.

Our research is centered on a particular type of bacterial membrane vesicle, known as the "outer membrane vesicle" (OMV), released by Porphyromonas gingivalis, a bacterium associated with the development of periodontal disease. These particles, with a diameter ranging from tens to hundreds of nanometers (approximately 1/10,000 of a millimeter), contain toxic proteins, lipids, and fragments of genetic information. These particles act as bacterial messengers, circulating throughout the body and potentially affecting distant tissues.

Of these, we are particularly focused on the brain, a "protected organ." The brain is firmly shielded from external influences by a robust barrier known as the "blood-brain barrier." However, it is hypothesized that Pg-OMVs (outer membrane vesicles derived from P. gingivalis) may possess a mechanism to penetrate this barrier. If Pg-OMVs penetrate this barrier and alter neuronal or vascular function, they may be involved in the development of diseases such as dementia and Alzheimer's disease. We have designated this concept the "Pg-OMV remote missile hypothesis" (Figure 1), and we are conducting research based on this hypothesis. Our objective is to verify at the molecular level the existence of this novel biological network, in which microparticles generated in the oral cavity travel throughout the body and affect distant organs without directly infecting bacteria.

Figure 1. The Remote Missile Hypothesis of Pg-OMVs (Schematic Diagram)

Our current research focuses on analyzing the pathway through which Pg-OMVs enter the brain, with a particular emphasis on their interaction with the cells that form the blood-brain barrier (endothelial cells). In the future, we plan to clarify what reactions occur after Pg-OMVs pass through cerebral blood vessels and how these affect brain function. The objective of this research is to gain a comprehensive understanding of the behavior of Pg-OMVs within the body and the signals they transmit.

Our primary objective is to elucidate the "invisible pathway" through which Pg-OMVs reach the brain and control that mechanism. Specifically, our objectives are to identify methods to regulate their binding to cell surfaces and their uptake into the oral cavity, as well as to reduce their excessive production in the oral cavity. By elucidating and controlling these pathways, we hope to be able to predict their effects on the brain early and potentially prevent dementia and Alzheimer's disease in the future. In this pioneering field at the intersection of dentistry and neuroscience, we will utilize robust data to delineate a novel medical framework that establishes a connection between the oral cavity and the rest of the body—a link that has remained obscured until now.

Pg-OMV solution, Culture medium used to grow P. gingivalis Image left: Pg-OMV solution
Image right: Culture medium used to grow P. gingivalis

Extraction of Pg-OMV

メンバー Members of Lecturer Ohkura Naoto's research team

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OHKURA Naoto

Senior Lecturer, Operative Dentistry and Endodontics, Niigata University Medical & Dental Hospital

Doctor of Dental Science. Specializes in endodontics. After graduating from the Graduate School of Medical and Dental Sciences at Niigata University, served as a Research Fellow at the University of Michigan, USA then was appointed as a lecturer in the Dental Consultation Department at Niigata University Medical and Dental Hospital in January 2025. We are developing methods to control this process by analyzing the pathways through which Pg-OMVs travel within the body and the mechanisms by which they cross biological barriers, and by clarifying their effects on the brain at the molecular level.

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*Article content and profile information are current as of November 2025