Elucidation of intestinal environment improvement mechanism by natural wound healing material using disease mouse model

• Project/Area Number: 20K11620
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 59040:Nutrition science and health science-related
• Research Institution: Tokyo University of Agriculture and Technology
• Principal Investigator: Shimizu Miho 東京農工大学, 工学(系)研究科(研究院), 客員准教授 (00500399)
• Co-Investigator(Kenkyū-buntansha): 藤田 恵理 東京農工大学, 工学(系)研究科(研究院), 研究員 (50466877) ; 跡見 順子 東京農工大学, 工学(系)研究科(研究院), 客員教授 (90125972)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 卵殻膜 / 炎症性腸疾患 / 細胞外マトリクス / III型コラーゲン / LSZ / 潰瘍性大腸炎モデル / 肺ー腸軸 / 腸内環境改善 / 腸内細菌叢 / IgA / 腸内環境 / 疾患マウスモデル / 創傷治癒 / ストレスタンパク質

Outline of Research at the Start

日常生活におけるストレスは、腸内環境にも影響を及ぼし腸内細菌叢の乱れ、炎症性腸疾患、慢性炎症、線維化から発癌につながる。従って腸内環境に同時多発的に働きかけて腸疾患の予防や治療につながる副作用のない安全な医薬の開発が急務である。本研究では、400年前から中国の薬学書本草項目に創傷治癒剤として掲載されている鶏卵殻膜に着目し、腸における炎症抑制メカニズムを、疾患モデルマウスを用いて明らかにする。

Outline of Final Research Achievements

Chicken eggshell membrane has been described as having wound-healing effects in pharmacological books dating back more than 400 years. Recently, it has been reported that eggshell membrane improves knee joint pain and prevents fibrosis and inflammation in animals. We have found that when humans ingest eggshell membrane as a supplement, the balance of intestinal microflora improves as well as respiratory function, skin elasticity, and locomotor function, and when mice are fed eggshell membrane as a supplement, the expression of soft type III collagen, which is secreted early in the wound healing process, increases The results were obtained. In this study, the intestinal environment improving effect of eggshell membrane leading to prevention was verified by the DSS colitis mouse model by prior ingestion of eggshell membrane.

Academic Significance and Societal Importance of the Research Achievements

炎症性腸疾患（IBD）は様々な腸の病気を含み、その中でも最も一般的なものは潰瘍性大腸炎（UC）とクローン病（CD）であり、持続性あるいは反復性の下痢、腹痛、血便などを伴う。近年、IBD患者は増えてきており、比較的若い年齢層（10～30歳代）で発症するため、栄養の吸収障害から成長障害をきたす可能性がある。本研究ではIBDのモデルとして最もよく用いられているDSS大腸炎モデルへの卵殻膜１日1回サプリメント的摂取が、病態悪化を防ぐ予防効果があることを示せた意義は大きい。

Research Products

• [Journal Article] Effect of Eggshell Membrane Powder Intake on the Body Function of Healthy Individuals (2021)
  • Author(s): Ohto-Fujita Eri、Hatakeyama Nozomi、Atomi Aya、Yasuda Shunsuke、Kodama Shoki、Atomi Tomoaki、Tanaka Kazuya、Noboru Hirose、Harada Kenji、Asano Yoshihide、Watanabe Toshiyuki、Hasebe Yukio、Shimizu Miho、Atomi Yoriko
  • Journal Title: Journal of Fiber Science and Technology Volume: 77 Issue: 10 Pages: 258-265
  • DOI: 10.2115/fiberst.2021-0029
  • NAID: 130008107353
  • ISSN: 2189-7654
  • Peer Reviewed / Open Access
• [Journal Article] 呼吸機能改善への天然素材卵殻膜を利用したアプローチ (2021)
  • Author(s): 大戸-藤田恵理, 清水美穂, 長谷部由紀夫, 跡見 順子
  • Journal Title: BIO Clinica Volume: 36 Pages: 52-56
• [Journal Article] Application of neutron-irradiated 6Li (n, α) 3H reaction to a protein-based fibrous non‐woven fabric biopolymer: Radiolabeling of cross-linked natural fibrous chicken eggshell membranes and their whole-body tissue distribution after oral ingestion in mice (2021)
  • Author(s): Eri Ohto-Fujita, Norio Nogawa, Miho Shimizu, Ken-ichi Ijiri, Yukio Hasebe, Yoriko Atomi
  • Journal Title: Journal of Fiber Science and Technology Volume: -
  • NAID: 130008052794
  • Peer Reviewed / Open Access
• [Presentation] 3H labeling of chick embryo ECM eggshell membranes by the recoil tag method and systemic tissue distribution after oral ingestion in mice (2021)
  • Author(s): 跡見順子, 大戸-藤田恵理, 野川憲夫, 清水美穂, 井尻憲一, 長谷部由紀夫
  • Organizer: 2021日本結合組織学会学術大会
• [Presentation] Radiolabeling of cross-linked natural fibrous chicken eggshell membranes and their whole-body tissue distribution after oral ingestion in mice (2021)
  • Author(s): Yoriko Atomi, Eri Ohto-Fujita, Norio Nogawa, Miho Shimizu, Ken-ichi Ijiri, Yukio Hasebe
  • Organizer: 2021 ASCB (CELL BIO virtual 2021, An online ASCB)
  • Int'l Joint Research
• [Presentation] ブレオマイシン肺線維症マウスモデルを用いた鶏卵殻膜摂取による抗線維化効果検証 (2020)
  • Author(s): 跡見順子、大戸-藤田恵理、柴山夏実、細田涼太、清水美穂、跡見綾、堀ノ内慎哉、宮崎新也、村上智亮、浅野善英、長谷部由紀夫
  • Organizer: 第52回日本結合組織学会学術大会（オンライン）
• [Presentation] Oral eggshell membrane administration attenuated lung fibrosis via type III collagen- and decorin-mediated wound healing (2020)
  • Author(s): Y Atomi, E Ohto-Fujita, M Shimizu, A Atomi, N Hatakeyama, N Shibayama, R Hosoda, S Horinouchi, T Murakami, S Miyazaki, M Kurimoto, S Yasuda, S Kodama, N Nogawa, T Atomi, K Tanaka, N Hirose, K Harada, Y Asano, T Watanabe, Y Hasebe
  • Organizer: Cell Bio 2020 Virtual-an Online ASCB|EMBO Meeting
  • Int'l Joint Research