NASH and gut microbiota

• Project/Area Number: 16K19357
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Gastroenterology
• Research Institution: Yokohama City University
• Principal Investigator: KESSOKU Takaomi 横浜市立大学, 附属病院, 助教 (30738620)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 腸内細菌 / 非アルコール性脂肪肝炎 / 腸管透過性 / NAFLD

Outline of Final Research Achievements

Up to 25% of NAFLD patients develop a progressive inflammatory liver disease termed non-alcoholic steatohepatitis (NASH) that may progress towards cirrhosis, hepatocellular carcinoma, and the need for liver transplantation. In recent years, several lines of evidence suggest that the gut microbiome plays important roles for the pathogenesis of NASH. We demonstrated faecalibacterium (FB) was significantly decreased with exacerbated liver fibrosis in human study. The aim of our study was to assess if FB improves NASH pathogenesis in mice and mechanism between FB and improving NASH-pathogenesis. Our study indicated that FB-administration improves NASH pathogenesis via ameliorating gut-permeability by inducingTreg in colon. Our results suggest that FB could be a candidate agent for the treatment of NASH through the improving leaky-gut.

Research Products

• [Journal Article] Pemafibrate, a novel selective peroxisome proliferator-activated receptor alpha modulator, improves the pathogenesis in a rodent model of nonalcoholic steatohepatitis. (2017)
  • Author(s): Honda Y, Kessoku T, Ogawa Y, Tomeno W, Imajo K, Fujita K, Yoneda M, Takizawa T, Saito S, Nagashima Y, Nakajima A.
  • Journal Title: Sci Rep. Volume: 7 Issue: 1 Pages: 42477-42477
  • DOI: 10.1038/srep42477
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [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] Metformin for chemoprevention of metachronous colorectal adenoma or polyps in post-polypectomy patients without diabetes: a multicentre double-blind, placebo-controlled, randomised phase 3 trial. (2016)
  • Author(s): Higurashi T, Hosono K, Takahashi H, Komiya Y, Umezawa S, Sakai E, Uchiyama T, Taniguchi L, Hata Y, Uchiyama S, Hattori A, Nagase H, Kessoku T, Arimoto J, Matsuhashi N, Inayama Y, Yamanaka S, Taguri M, Nakajima A.
  • Journal Title: Lancet Oncol. Volume: 17 Issue: 4 Pages: 475-783
  • DOI: 10.1016/s1470-2045(15)00565-3
  • Peer Reviewed / Open Access / Int'l Joint Research
• [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] The Selective SGLT2 Inhibitor Ipragliflozin Has a Therapeutic Effect on Nonalcoholic Steatohepatitis in Mice. (2016)
  • Author(s): Honda Y, Imajo K, Kato T, et al.
  • Journal Title: PLoS One Volume: 11 Issue: 1 Pages: e0146337-e0146337
  • DOI: 10.1371/journal.pone.0146337
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] The characteristics of non-obese NAFLD: Effect of genetic and environmental factors. (2016)
  • Author(s): Honda Y, Yoneda M, Kessoku T, Ogawa Y, Tomeno W, Imajo K, Mawatari H, Fujita K, Hyogo H, Ueno T, Chayama K, Saito S, Nakajima A, Hotta K
  • Journal Title: Hepatol Res Volume: - Issue: 10 Pages: 636-636
  • DOI: 10.1111/hepr.12648
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] The aggravation of nonalcoholic fatty liver disease is associated with endotoxemia via the increase of gut-permeability by faecalibacterium prausnittii in human and vivo study (2016)
  • Author(s): Takaomi Kessoku
  • Organizer: Asian Pacific Digestive Week
  • Place of Presentation: Kobe Convention Center (兵庫県神戸市)
  • Year and Date: 2016-11-03
• [Presentation] 非アルコール性脂肪肝疾患患者の腸内細菌叢に関する検討. (2016)
  • Author(s): 結束貴臣
  • Organizer: 第52回 日本肝臓学会総会. WS5：NASH/NAFLD研究の新展開.
  • Place of Presentation: 幕張メッセ（千葉県幕張市）
  • Year and Date: 2016-04-22
• [Presentation] 非アルコール性脂肪肝炎の線維化進展に寄与する腸内細菌叢の検討. (2016)
  • Author(s): 結束貴臣
  • Organizer: 第102回 日本消化器病学会総会. ワークショップ3
  • Place of Presentation: 京王プラザホテル（東京都新宿区）
  • Year and Date: 2016-04-21
• [Presentation] CHARACTERISTICS OF FECAL MICROBIOTA IN NONALCOHOLIC FATTY LIVER DISEASE (NAFLD) PATIENTS: A CONNECTION BETWEEN ENDOTOXIN AND NAFLD. (2016)
  • Author(s): Takaomi Kessoku
  • Organizer: The International Liver Congress2016 - 51st annual meeting of the European Association for the Study of the Liver (EASL)
  • Place of Presentation: バルセロナ、スペイン
  • Year and Date: 2016-04-16
  • Int'l Joint Research