Identification of the Th17 cell-inducing bacteria from IBD patients

• Project/Area Number: 15H05657
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Immunology
• Research Institution: Keio University
• Principal Investigator: Atarashi Koji 慶應義塾大学, 医学部(信濃町), 准教授 (60546787)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥24,180,000 (Direct Cost: ¥18,600,000、Indirect Cost: ¥5,580,000); Fiscal Year 2017: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000); Fiscal Year 2016: ¥8,190,000 (Direct Cost: ¥6,300,000、Indirect Cost: ¥1,890,000); Fiscal Year 2015: ¥9,360,000 (Direct Cost: ¥7,200,000、Indirect Cost: ¥2,160,000)
• Keywords: Th17細胞 / microbiota / IBD / 腸内細菌 / 粘膜免疫 / 炎症性腸疾患 / Th17

Outline of Final Research Achievements

Th17 cells play a role in host defense against extracellular pathogens and also pathogenesis of multiple inflammatory and autoimmune disorders. I have identified the human gut bacteria that could induce intestinal Th17 cells. Th17 cells were significantly increased in the colon of the germ-free mice inoculated with fecal samples from Ulcerative colitis (UC) patients. This Th17 cell induction was further enhanced when the mice were treated with Ampicillin (Amp) in the drinking water. To isolate Th17-inducing bacterial species, I cultured cecal contents from these UC feces colonized and Amp treated mice. I isolated 20 bacterial strains belonging to Clostridium, Bifidobacterium, Ruminococcus, and Bacteroides and inoculated germ-free mice with these 20 strains. The colonization of these 20 strains strongly induced a robust accumulation of Th17 cells in the colon. Furthermore, nine out of the 20 strains were significantly increased in the microbiomes of UC and Crohn’s disease subjects.

Research Products

• [Journal Article] Ectopic colonization of oral bacteria in the intestine drives TH1 cell induction and inflammation" Ectopic colonization of oral bacteria in the intestine drives TH1 cell induction and inflammationx (2017)
  • Author(s): Atarashi K, Suda W, Luo C, Kawaguchi T, Motoo I, Narushima S, Kiguchi Y, Yasuma K, Watanabe E, Tanoue T, Thaiss CA, Sato M, Toyooka K, Said HS, Yamagami H, Rice SA, Gevers D, Johnson RC, Segre JA, Chen K, Kolls JK, Elinav E, Morita H, Xavier RJ, Hattori M, Honda K.
  • Journal Title: Science Volume: 358 Issue: 6361 Pages: 359-365
  • DOI: 10.1126/science.aan4526
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Maternal gut bacteria promote neurodevelopmental abnormalities in mouse offspring (2017)
  • Author(s): Kim S, Kim H, Yim YS, Ha S, Atarashi K, Tan TG, Longman RS, Honda K, Littman DR, Choi GB, Huh JR
  • Journal Title: Nature Volume: 549 Issue: 7673 Pages: 528-532
  • DOI: 10.1038/nature23910
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] A subpopulation of high IL-21-producing CD4(+) T cells in Peyer's Patches is induced by the microbiota and regulates germinal centers. (2016)
  • Author(s): Jones L, Ho WQ, Ying S, Ramakrishna L, Srinivasan KG, Yurieva M, Ng WP, Subramaniam S, Hamadee NH, Joseph S, Dolpady J, Atarashi K, Honda K, Zolezzi F, Poidinger M, Lafaille JJ, Curotto de Lafaille MA.
  • Journal Title: Scientific Reports Volume: 6 Issue: 1 Pages: 30784-30784
  • DOI: 10.1038/srep30784
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A Diet-dependent, microbiota-independent regulation of IL-10-producing lamina propria macrophages in the small intestine (2016)
  • Author(s): Ochi T, Feng Y, Kitamoto S, Nagao-Kitamoto H, Kuffa P, Atarashi K, Honda K, Teitelbaum DH, Kamada N
  • Journal Title: Scientific Reports Volume: 6 Issue: 1 Pages: 27634-27634
  • DOI: 10.1038/srep27634
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Th17 Cell induction by adhesion of microbes to intestinal epithelial cells (2015)
  • Author(s): Atarashi, K., Tanoue, T., Ando. M., Kamada, N., Nagano, Y., Narushima, S., Suda, W., Imaoka, A., Setoyama, H., Nagamori, T., Ishikawa, E., Shima, T., Hara, T., Kado, S., Jinnohara, T., Ohno, H., Kondo, T. et al.
  • Journal Title: Cell Volume: 163 Issue: 2 Pages: 367-380
  • DOI: 10.1016/j.cell.2015.08.058
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] 口腔由来クレブシエラ菌の腸内定着と炎症誘導 (2018)
  • Author(s): 新幸二
  • Organizer: 第 27 回東京免疫フォーラム
  • Invited
• [Presentation] ヒト腸内フローラと免疫機能 (2017)
  • Author(s): 新幸二
  • Organizer: (公社)日本実験動物学会 維持会員懇談会
  • Invited
• [Presentation] 口腔細菌による腸管免疫系活性化機構の解明 (2016)
  • Author(s): 新幸二
  • Organizer: 第89回日本生化学会大会
  • Place of Presentation: 仙台国際センター（宮城県仙台市）
  • Year and Date: 2016-09-26
  • Invited
• [Presentation] 口腔内細菌による腸管免疫活性化機構の解明 (2016)
  • Author(s): 新幸二
  • Organizer: フォーラム2016 衛生薬学・環境トキシコロジー
  • Place of Presentation: 昭和大学旗の台キャンパス（東京都品川区）
  • Year and Date: 2016-09-26
  • Invited