The development of new treatments using probiotics-derived molecules for intestinal fibrosis based on an analysis of its mechanisms

• Project/Area Number: 15K19306
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Gastroenterology
• Research Institution: Asahikawa Medical College
• Principal Investigator: Kashima Shin 旭川医科大学, 医学部, 助教 (10548655)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2016: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2015: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: プロバイオティクス / 消化管線維化 / ポリリン酸 / Ferrichrome / マクロファージ / 菌由来活性物質 / 腸内細菌

Outline of Final Research Achievements

I explored the effective molecules derived from probiotic conditioned-media and identified ferrichrome as a candidate anti-fibrotic molecule. However, ferrichrome did not exhibit an anti-fibrotic function, although it did have a strong anti-tumor function. A bioactive polyphosphate derived from Lactobacillus brevis exhibited an anti-inflammatory function through the regulation of TLR4-IFNα/β-JAK/STAT signaling. I have not identified new materials derived from probiotics in this study but will continue to search for new anti-inflammatory antifibrosis materials derived from effective molecules exhibiting anti-fibrotic activity in probiotic conditioned-media.

Research Products

• [Journal Article] An elevated expression of serum exosomal microRNA-191, -21, -451a of pancreatic neoplasm is considered to be efficient diagnostic marker (2018)
  • Author(s): Goto Takuma、Fujiya Mikihiro、Konishi Hiroaki、Sasajima Junpei、Fujibayashi Shugo、Hayashi Akihiro、Utsumi Tatsuya、Sato Hiroki、Iwama Takuya、Ijiri Masami、Sakatani Aki、Tanaka Kazuyuki、Nomura Yoshiki、Ueno Nobuhiro、Kashima Shin、Moriichi Kentaro、Mizukami Yusuke、Kohgo Yutaka、Okumura Toshikatsu
  • Journal Title: BMC Cancer Volume: 18 Issue: 1 Pages: 1-11
  • DOI: 10.1186/s12885-018-4006-5
  • Peer Reviewed / Open Access
• [Journal Article] Ferrichrome identified from Lactobacillus casei ATCC334 induces apoptosis through its iron-binding site in gastric cancer cells (2017)
  • Author(s): Ijiri Masami、Fujiya Mikihiro、Konishi Hiroaki、Tanaka Hiroki、Ueno Nobuhiro、Kashima Shin、Moriichi Kentaro、Sasajima Junpei、Ikuta Katsuya、Okumura Toshikatsu
  • Journal Title: Tumor Biology Volume: 39 Issue: 6 Pages: 101042831771131-101042831771131
  • DOI: 10.1177/1010428317711311
  • NAID: 120006473651
  • Peer Reviewed / Open Access
• [Journal Article] A meta-analysis of efficacy and adverse events of cold vs. hot polypectomy. (2016)
  • Author(s): Fujiya M, Sato H, Ueno N, Sakatani A, Tanaka K, Dokoshi T, Fujibayashi S, Nomura Y, Kashima S, Gotoh T, Sasajima J, Moriichi K, Watari J, Kohgo Y.
  • Journal Title: World Journal of Gastroenterology Volume: 21 Issue: 23 Pages: 5436-44
  • DOI: 10.3748/wjg.v22.i23.5436
  • Peer Reviewed / Open Access
• [Journal Article] Syphilis infection throughout the whole gastrointestinal tract. (2016)
  • Author(s): Ijiri M, Fujiya M, Ueno N, Kashima S, Watari T, Fujii S, Okumura T.
  • Journal Title: Endoscopy Volume: 48 Issue: S 01 Pages: E338-E339
  • DOI: 10.1055/s-0042-117715
  • Peer Reviewed / Open Access
• [Journal Article] Quantification of autofluorescence imaging can accurately and objectively assess the severity of ulcerative colitis. (2015)
  • Author(s): Moriichi K, Fujiya M, Ijiri M, Tanaka K, Sakatani A, Dokoshi T, Fujibayashi S, Ando K, Nomura Y, Ueno N, Kashima S, Gotoh T, Sasajima J, Inaba Y, Ito T, Tanabe H, Saitoh Y, Kohgo Y.
  • Journal Title: Int J Colorectal Dis. Volume: 30 Issue: 12 Pages: 1639-1643
  • DOI: 10.1007/s00384-015-2332-5
  • Peer Reviewed / Open Access
• [Journal Article] A Bamboo Joint-Like Appearance is a Characteristic Finding in the Upper Gastrointestinal Tract of Crohn's Disease Patients: A Case-Control Study. (2015)
  • Author(s): Fujiya M, Sakatani A, Dokoshi T, Tanaka K, Ando K, Ueno N, Gotoh T, Kashima S, Tominaga M, Inaba Y, Ito T, Moriichi K, Tanabe H, Ikuta K, Ohtake T, Yokota K, Watari J, Saitoh Y, Kohgo Y.
  • Journal Title: medicine Volume: 94 Issue: 37 Pages: e1500-e1500
  • DOI: 10.1097/md.0000000000001500
  • Peer Reviewed / Open Access
• [Journal Article] Probiotic-derived polyphosphate improves the intestinal barrier function through the caveolin-dependent endocytic pathway. (2015)
  • Author(s): Tanaka K, Fujiya M, Konishi H, Ueno N, Sasajima J, Moriichi K, Ikuta K, Tanabe H, Kohgo Y.
  • Journal Title: Biochem Biophys Res Commun Volume: 467 Issue: 3 Pages: 541-548
  • DOI: 10.1016/j.bbrc.2015.09.159
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Polyphosphate Derived from Lactobacillus brevis Inhibits Colon Cancer Progression Through Induction of Cell Apoptosis. (2015)
  • Author(s): Sakatani A, Fujiya M, Ueno N, Kashima S, Sasajima J, Moriichi K, Ikuta K, Tanabe H, Kohgo Y.
  • Journal Title: Anticancer Res Volume: 36 Pages: 591-598
  • Peer Reviewed / Open Access
• [Presentation] インフリキシマブバイオシミラー投与におけるクローン病患者のQOL から見た妥当性の検討 (2017)
  • Author(s): "杉山雄哉、上野伸展、岩間琢哉、田中一之、高橋慶太郎、野村好紀、嘉島伸、盛一健太郎、藤谷幹浩、奥村利勝 "
  • Organizer: 第8回日本炎症性腸疾患学会
• [Presentation] 顆粒球除去療法の効果予測マーカーとしての便中カルプロテクチン測定の意義 (2017)
  • Author(s): 上野伸展、杉山雄哉、岩間琢哉、井尻学見、田中一之、高橋慶太郎、安藤勝祥、野村好紀、嘉島伸、盛一健太郎、藤谷幹浩、奥村利勝
  • Organizer: 第8回日本炎症性腸疾患学会
• [Presentation] 潰瘍性大腸炎における炎症状態評価に有用なCT重症度scoreの検討 (2017)
  • Author(s): 杉山雄哉，嘉島伸，岩間琢哉，井尻学見，田中一之，高橋慶太郎，安藤勝祥，野村好紀，上野伸展，盛一健太郎，藤谷幹浩，奥村利勝
  • Organizer: JDDW2017
• [Presentation] "消化管悪性リンパ腫の診断と治療効果判定におけるNarrow Band Imaging (NBI)の有用性 " (2017)
  • Author(s): "嘉島 伸，藤谷幹浩，岩間琢哉，井尻学見，高橋慶太郎，田中一之，坂谷慧，安藤勝祥，野村好紀，上野伸展，盛一健太郎，奥村利勝 "
  • Organizer: 第93回日本消化器内視鏡学会総会
• [Presentation] 炎症性腸疾患入院患者における静脈血栓塞栓症の発症頻度とリスク層別化についての検討 (2017)
  • Author(s): 安藤勝祥、野村好紀、杉山雄哉、岩間琢哉、井尻学見、田中一之、高橋慶太郎、上野伸展、嘉島 伸、盛一健太郎、藤谷幹浩、奥村利勝
  • Organizer: JDDW2017