Prediction and prevention of serious systemic diseases induced by local infection of bacteria

• Project/Area Number: 15H04757
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Applied pharmacology
• Research Institution: Shimane University
• Principal Investigator: Wada Koichiro 島根大学, 医学部, 教授 (90263467)
• Co-Investigator(Kenkyū-buntansha): 中島 淳 横浜市立大学, 医学研究科, 教授 (30326037) ; 今城 健人 横浜市立大学, 附属病院, 助教 (30600192) ; 田中 徹也 島根大学, 医学部, 助教 (10346380) ; 立花 雅史 大阪大学, 薬学研究科, 特任准教授(常勤) (80513449)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000); Fiscal Year 2017: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2016: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2015: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
• Keywords: 全身疾患 / 局所感染 / 口腔細菌 / 循環器疾患 / 脳卒中 / 糖尿病 / ＮＡＳＨ / 口腔-腸相関 / 口腔内細菌 / 消化器疾患 / NASH / 感染症 / 免疫学 / 生理活性 / 循環器・高血圧 / 薬理学 / 全身疾患誘発 / 免疫異常 / 炎症性腸疾患

Outline of Final Research Achievements

There are few reports about the role of oral microbiota on the human health and systemic diseases. We, therefore, investigated roles of infection of high-virulent oral bacteria on the development of serious systemic diseases such as stroke, cardiovascular, and digestive diseases. Relationships between the prevalence of several high-virulent bacteria and several systemic diseases were observed. According to the exhaustive analysis of oral flora using next generation sequencer, different patterns of oral flora between the healthy subjects and the subjects with various chronic diseases were observed. These results indicate that the balance of total composition of oral flora might be important for maintenance of human health condition. Further investigations will provide us the important knowledge to predict and prevent various systemic diseases in future.

Research Products

• [Journal Article] Oral microbiome alterations of healthy volunteers with proton pump inhibitor (2018)
  • Author(s): Mishiro Tsuyoshi、Oka Kentaro、Kuroki Yasutoshi、Takahashi Motomichi、Tatsumi Kasumi、Saitoh Tsukasa、Tobita Hiroshi、Ishimura Norihisa、Sato Shuichi、Ishihara Shunji、Sekine Joji、Wada Koichiro、Kinoshita Yoshikazu
  • Journal Title: J Gastroenterol Hepatol. Volume: 33 Issue: 5 Pages: 1059-1066
  • DOI: 10.1111/jgh.14040
  • Peer Reviewed / Open Access
• [Journal Article] Efficacy, safety, and tolerability of lubiprostone for the treatment of non-alcoholic fatty liver disease in adult patients with constipation (2018)
  • Author(s): Kessoku T, Imajo K, Kobayashi T, Honda Y, Kato T, Ogawa Y, Tomeno W, Kato S, Higurashi T, Yoneda M, Kirikoshi H, Kubota K, Taguri M, Yamanaka T, Usuda H, Wada K, Saito S, Nakajima A.
  • Journal Title: Contemporary clinical trials Volume: 69 Pages: 40-47
  • DOI: 10.1016/j.cct.2018.04.002
  • Peer Reviewed / Open Access
• [Journal Article] Wisteria floribunda agglutinin-positive Mac-2 binding protein and type 4 collagen 7S are useful markers for the diagnosis of significant fibrosis in patients with nonalcoholic fatty liver disease. (2018)
  • Author(s): Ogawa Y, Honda Y, Kessoku T, Tomeno W, Imajo K, Yoneda M, Kawanaka M, Kirikoshi H, Ono M, Taguri M, Saito S, Yamanaka T, Wada K, Nakajima A.
  • Journal Title: J Gastroenterol Hepatol. Volume: in press Issue: 10 Pages: 1795-1803
  • DOI: 10.1111/jgh.14156
  • Peer Reviewed / Open Access
• [Journal Article] Reduced substrate stiffness promotes M2-like macrophage activation and enhances peroxisome proliferator-activated receptor-gamma expression (2018)
  • Author(s): Okamoto T, Takagi Y, Kawamoto E, Park EJ, Usuda H, Wada K, Shimaoka M
  • Journal Title: Experimental Cell Research Volume: 367 Issue: 2 Pages: 264-273
  • DOI: 10.1016/j.yexcr.2018.04.005
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Therapeutic strategies for intractable digestive diseases: importance of disease models for evaluation of drug efficacy (2017)
  • Author(s): 和田 孝一郎, 臼田 春樹
  • Journal Title: Folia Pharmacologica Japonica Volume: 150 Issue: 4 Pages: 183-187
  • DOI: 10.1254/fpj.150.183
  • NAID: 130006107982
  • ISSN: 0015-5691, 1347-8397
  • Peer Reviewed / Open Access
• [Journal Article] Lubiprostone improves intestinal permeability in humans, a novel therapy for the leaky gut: A prospective randomized pilot study in healthy volunteers. (2017)
  • Author(s): Kato T, Honda Y, Kurita Y, Iwasaki A, Sato T, Kessoku T, Uchiyama S, Ogawa Y, Ohkubo H, Higurashi T, Yamanaka T, Usuda H, Wada K, Nakajima A.
  • Journal Title: PLoS One Volume: 12（4） Issue: 4 Pages: e0175626-e0175626
  • DOI: 10.1371/journal.pone.0175626
  • Peer Reviewed / Open Access
• [Journal Article] Characteristics of fecal microbiota in non-alcoholic fatty liver disease (NAFLD) patients: A connection between endotoxin and NAFLD. (2016)
  • Author(s): Kessoku T, Imajo K, Honda Y, Ogawa Y, Kato T, Endo H, Wada K, Nakajima A.
  • Journal Title: Journal of Hepatology Volume: 64
  • Peer Reviewed
• [Journal Article] Resveratrol ameliorates fibrosis and inflammation in a mouse model of nonalcoholic steatohepatitis. (2016)
  • Author(s): Kessoku T, Imajo K, Honda Y, et al.
  • Journal Title: Sci Rep Volume: 25 Issue: 1 Pages: 22251-22251
  • DOI: 10.1038/srep22251
  • NAID: 120005749754
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Magnetic Resonance Imaging More Accurately Classifies Steatosis and Fibrosis in Nonalcoholic Fatty Liver Disease Than Transient Elastography. (2016)
  • Author(s): Imajo K, Kessoku T, Honda Y, Tomeno W, Ogawa Y, Mawatari H, Fujita K, Yoneda M, Taguri M, Hyogo H, Sumida Y, Ono M, Eguchi Y, Inoue T,Yamanaka T, Wada K, Saito S, Nakajima A
  • Journal Title: Gastroenterology Volume: 150 Issue: 3 Pages: 626-37
  • DOI: 10.1053/j.gastro.2015.11.048
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Deficiency of eNOS exacerbates early-stage NAFLD pathogenesis by changing the fat distribution. (2015)
  • Author(s): Nozaki Y, Fujita K, Wada K, Yoneda M, Shinohara Y, Imajo K, Ogawa Y, Kessoku T, Nakamuta M, Saito S, Masaki N, Nagashima Y, Terauchi Y, Nakajima A.
  • Journal Title: BMC Gastroenterol Volume: 17 Issue: 1 Pages: 177-177
  • DOI: 10.1186/s12876-015-0409-9
  • Peer Reviewed / Open Access
• [Presentation] Gut microbiota and nonalcoholic fatty liver disease. (2017)
  • Author(s): 結束貴臣、今城健人、本田靖、小川祐二、留野渉、米田正人、斉藤聡、臼田春樹、和田孝一郎、中島淳
  • Organizer: 第90回 日本薬理学会年会 シンポジウム
  • Place of Presentation: （長崎市） 長崎新聞文化ホールアストピア
  • Year and Date: 2017-03-15
• [Presentation] Leaky Gut Syndrome を誘発する要因とその全身への影響. (2017)
  • Author(s): 和田孝一郎
  • Organizer: 黒潮カンファレンス
  • Invited
• [Presentation] Porphyromonas gingivalis の保菌は糖尿病の重症度と相関する. (2017)
  • Author(s): 臼田春樹, 新林友美, 岡本貴行, 和田孝一郎.
  • Organizer: 黒潮カンファレンス
• [Presentation] Leaky Gut Syndrome を誘発する要因とその全身疾患への進展―薬物・腸内細菌・血流を中心として―. (2017)
  • Author(s): 和田孝一郎
  • Organizer: 大阪臨床薬理研究会
  • Invited
• [Presentation] 我々の健康に影響を与える口腔内細菌と腸内細菌―健康長寿のカギは我々が持っている細菌がにぎっているのか？―. (2017)
  • Author(s): 和田孝一郎
  • Organizer: 医療・健康・福祉―工学技術連携可能性懇話会
  • Invited
• [Presentation] 薬力学の知識とドラッグデリバリーシステム： 薬力学の理論と臨床応用 (2016)
  • Author(s): 和田孝一郎
  • Organizer: 第30回 日本耳鼻科咽喉科学会専門医講習会 教育講演
  • Place of Presentation: （広島市） 広島国際会議場
  • Year and Date: 2016-11-12
  • Invited
• [Presentation] 口腔細菌が関連する循環器疾患 (2016)
  • Author(s): 和田孝一郎
  • Organizer: 第39回 日本高血圧学会総会 シンポジウム
  • Place of Presentation: （仙台市） 仙台国際センター
  • Year and Date: 2016-09-30
  • Invited
• [Presentation] 腸管透過性を介した非アルコール性脂肪肝炎の病態進展における腸内細菌叢とエンドトキシンの関連性の検討 (2016)
  • Author(s): 結束貴臣、今城健人、本多靖、加藤孝征、小川祐二、留野渉、嶋川真木、田中良紀、及川洋祐、大野裕史、臼田春樹、日暮琢磨、遠藤宏樹、米田正人、斉藤聡、和田孝一郎、中島淳
  • Organizer: 第53回 日本消化器免疫学会総会
  • Place of Presentation: （大阪市） ホテルニューオータニ大阪
  • Year and Date: 2016-07-14
• [Presentation] Therapeutic strategies for intractable digestive diseases. (2016)
  • Author(s): 和田孝一郎、臼田春樹
  • Organizer: 第 89 回日本薬理学会年会 シンポジウム
  • Place of Presentation: 横浜市（パシフィコ横浜 会議センター）
  • Year and Date: 2016-03-09
• [Presentation] 口腔細菌によってひきおこされる全身疾患 ―脳卒中からNASHまで― (2016)
  • Author(s): 和田孝一郎
  • Organizer: 益田鹿足歯科医師会 講演会
  • Place of Presentation: （益田市） 益田地区医療センター医師会病院
  • Invited
• [Presentation] 健康に影響を与える腸内細菌と口腔細菌 (2016)
  • Author(s): 和田孝一郎
  • Organizer: 第60回 島根県保険医協会出雲支部 講演会
  • Place of Presentation: （出雲市） ニューウェルシティ出雲
  • Invited
• [Presentation] NASH/NAFLD関連マイクロRNA miR-27bの脂質蓄積促進能を担う標的遺伝子の解析 (2015)
  • Author(s): 鈴木 瑠々香, 酒井 英子, 立花 雅史, 櫻井 文教, 結束 貴臣, 中島 淳, 和田 孝一郎, 水口 裕之
  • Organizer: ＢＭＢ2015
  • Place of Presentation: 神戸市（神戸ポートアイランド国際会議場）
  • Year and Date: 2015-12-01
• [Book] プリンシプル消化器疾患の臨床 「食道・胃・十二指腸の診療アップデート」 (2017)
  • Author(s): 木下芳一、佐々木裕 編集、 和田孝一郎 ほか
  • Total Pages: 330
  • Publisher: 中山書店
• [Book] 腸内細菌・口腔細菌と全身疾患 (2015)
  • Author(s): 落合邦康 監修、結束貴臣、和田孝一郎、他
  • Total Pages: 259
  • Publisher: シーエムシー出版
• [Remarks] 口腔内細菌と全身疾患との関連
  • URL: http://www.med.shimane-u.ac.jp/pharmacology/kenkyuusyokai-oralbiome.html
• [Remarks] 島根大学 地域包括ケア教育研究センター
  • URL: http://www.cohre.jp/research/217
• [Patent(Industrial Property Rights)] 腸粘膜の透過性の診断薬、診断方法、診断装置 (2017)
  • Inventor(s): 和田孝一郎 ほか
  • Industrial Property Rights Holder: 和田孝一郎 ほか
  • Industrial Property Rights Type: 特許
  • Filing Date: 2017