Study on the invasion of periodontal disease related bacteria into the brain

• Project/Area Number: 17K17362
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Periodontology
• Research Institution: Matsumoto Dental University
• Principal Investigator: ishida naoyuki 松本歯科大学, 歯学部, 助教 (50757622)
• Project Period (FY): 2017-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 歯周病 / アルツハイマー病 / Porphyromonas gingivalis / 血液脳関門 / lipopolysaccharide / 腸内細菌 / Lipopolysaccharide / Blood Brain Barrier / zonulin / 大腸菌

Outline of Final Research Achievements

Our previous studies show that periodontitis caused by infection with periodontitis-related bacteria Porphyromonas ginigvalis (P. gingivalis) exacerbates the pathological features of Alzheimer's disease (AD) in a mouse model Indicated. However, there have been no studies to examine the mechanism.
As a result of this study, it was found that P. ginigvalis and its bacterial endotoxin lipopolysaccharide (LPS) increase the permeability of blood-brain barrier. Furthermore, it was suggested about the mechanism by which the LPS causes inflammation in the brain and aggravates the pathological condition of AD.

Academic Significance and Societal Importance of the Research Achievements

アルツハイマー病(AD)の原因物質とされる脳内のアミロイドβの沈着は、AD患者における認知障害の発症の20年以上前の40歳代前半に開始される。本研究により、この期間中に歯周病の治療を行う事によって、ADの発症または進行を遅らせるのに有効であり得ることが示唆された。
また、歯周病関連細菌LPSの血流への侵入経路として、腸内の関門を通過して侵入している可能性が示唆された。
以上のことから、壮年期からの歯周病のケアと並行して良好な腸内環境を維持していくこともADの発症予防に貢献する可能性があると考えられる。

Research Products

• [Journal Article] Periodontal disease exacerbates Alzheimer's disease (2018)
  • Author(s): Ishida Naoyuki、Yoshinari Nobuo、Matsushita Kenji、Ishihara Yuichi
  • Journal Title: Nihon Shishubyo Gakkai Kaishi (Journal of the Japanese Society of Periodontology) Volume: 60 Issue: 3 Pages: 147-152
  • DOI: 10.2329/perio.60.147
  • NAID: 130007492010
  • ISSN: 0385-0110, 1880-408X
  • Year and Date: 2018-09-28
  • Peer Reviewed / Open Access
• [Journal Article] Periodontitis induced by bacterial infection exacerbates features of Alzheimer's disease in transgenic mice (2017)
  • Author(s): Ishida N, Ishihara Y, Ishida K, Tada H, Funaki-Kato Y, Hagiwara M, Ferdous T, Abdullah M, Mitani A, Michikawa M, Matsushita K.
  • Journal Title: NPJ Aging Mech. Dis. Volume: 3 Issue: 1 Pages: 15-15
  • DOI: 10.1038/s41514-017-0015-x
  • NAID: 120006576159
  • Peer Reviewed / Open Access / Int'l Joint Research