Novel Therapeutic Targets for Functional Gastrointestinal Disorders

• Project/Area Number: 18K08019
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Hyogo Medical University
• Principal Investigator: Takashi Kondo 兵庫医科大学, 医学部, 講師 (90594870)
• Co-Investigator(Kenkyū-buntansha): 三輪 洋人 兵庫医科大学, 医学部, 教授 (80190833)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 機能性消化管疾患 / 内臓知覚過敏

Outline of Final Research Achievements

The underlying mechanism between micro-inflammation and FD remains unknown. In this study, using a maternal separation (MS)-induced FD model, we aimed to reproduce the gastroduodenal micro-inflammation and reveal the interaction of gastroduodenal micro-inflammation and gastric hypersensitivity. MS model was established by separating newborn Sprague Dawley rats for 2 h a day from postnatal day 1 to 10. At 7-8 weeks of age, electromyography was used to determine the visceromotor response to gastric distention (GD). MS-induced FD rats underwent gastric hypersensitivity with GD. Eosinophils were significantly increased in the gastroduodenal tract. Treatment with dexamethasone reversed gastric hypersensitivity in MS-induced FD rats by inhibiting eosinophil infiltration. Our results indicate that neonatal MS stress induces eosinophil-associated gastroduodenal micro-inflammation and gastric hypersensitivity at adulthood in rats. Micro-inflammation contributes to gastric hypersensitivity.

Academic Significance and Societal Importance of the Research Achievements

今回の研究成果により，生直後のストレスが引き金となり，成長後に胃十二指腸粘膜内での好酸球増加を主とする微小炎症を引き起こすこと，その結果として胃十二指腸粘膜の知覚過敏に結びついている可能性が示唆された。このことは，機能性消化管疾患患者の症状発現メカニズムの病態解明に結びつき新たな治療ターゲットの発見に結びつくものと考える。

Research Products

• [Journal Article] Eosinophil-associated microinflammation in the gastroduodenal tract contributes to gastric hypersensitivity in a rat model of early-life adversity (2021)
  • Author(s): Duan Shaoqi、Kondo Takashi、Miwa Hiroto、Yang Yanjing、Wang Shenglan、Kanda Hirosato、Kogure Yoko、Imamura Nobuko、Fujimura Tadahiro、Kono Tomoaki、Fukushima Masashi、Tozawa Katsuyuki、Tomita Toshihiko、Oshima Tadayuki、Fukui Hirokazu、Yamamoto Satoshi、Noguchi Koichi、Dai Yi
  • Journal Title: American Journal of Physiology-Gastrointestinal and Liver Physiology Volume: 320 Issue: 2 Pages: G206-G216
  • DOI: 10.1152/ajpgi.00313.2020
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Early-Life Adversity Inducesd Sex-Dependent Gastric Hyprsensitivity. (2019)
  • Author(s): Shaoqi Duan, Takashi Kondo, Yanjing Yang, Shenglan Wang, Yoko Kogure, Tomoaki Kono, Katsuyuki Tozawa, Toshihiko Tomita, Tadayuki Oshima, Hirokazu Fukui, Jiro Watari, Yi Dai, Koichi Noguchi, Hiroto Miwa
  • Organizer: Digestive Disease Week, San Diego, CA, USA
  • Int'l Joint Research
• [Presentation] Early-life stress induced gastric hypersensitivity in adult rats. International Session (2019)
  • Author(s): Takashi Kondo, Shaoqi Duan, Hiroto Miwa
  • Organizer: Japan Digestive Disease Week (JDDW) 2019，Kobe, Japan
  • Int'l Joint Research
• [Presentation] Effect of Yokukansan, a traditional herbal medicine, on gastric hypersensitivity in a rodent model of functional dyspepsia (2019)
  • Author(s): Takashi Kondo, Shaoqi Duan, Hirokazu Eda, Kumiko Nakamura, Akio Tamura, Tomoaki Ogawa, Takashisa Yamasaki, Tomoaki Kono, Katsuyuki Tozawa, Toshihiko Tomita, Tadayuki Oshima, Hirokazu Fukui, Jiro Watari, Yi Dai, Koichi Noguchi, Hiroto Miwa
  • Organizer: Asian Pacific Digestive Week（APDW）2019, Kolkata, India
  • Int'l Joint Research