Bile acid metabolism by intestinal microbiota

• Project/Area Number: 16K08091
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Integrative animal science
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: Narushima Seiko 国立研究開発法人理化学研究所, 生命医科学研究センター, 副チームリーダー (80578336)
• Research Collaborator: Atarashi koji ; Ogura yoshio ; Suda wataru
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 腸内細菌 / ノトバイオートマウス / 胆汁酸 / ノトバイオート / 胆汁酸代謝

Outline of Final Research Achievements

The development and the function of intestinal cells are affected by the presence of the gut microbiota. Bile acids are synthesized from cholesterol in the liver, conjugated, and secreted into the small intestine where they play an important role in nutrient absorption. Bile acids are also very important regulators of host metabolism by acting as signaling molecules in various organs via specific receptors FXR and TGR5. Total bile acid levels and the relative proportions of primary and secondary bile acids vary significantly among the feces of healthy donors, depending their own microbiota. We have identified bacterial strains capable of converting primary bile acids into particular secondary bile acids from the feces of ex-GF mice associated with human feces of particular bile acid profiles, which provide a substantial impact on the signaling function of the host. The findings would be of potential therapeutic value in controlling host metabolism.

Academic Significance and Societal Importance of the Research Achievements

胆汁酸は腸内に常在する菌により変換されるが、変換の経路や、変換を担う菌については不明な点が多く、また変換された胆汁酸が宿主の健康や病態に与える影響についての詳細な解析は未だ不十分である。本研究では、偏性嫌気性菌の培養技術と無菌マウスを用いて、菌による胆汁酸変換と宿主へ及ぼす影響について解析を行った。健常なヒトにおいても腸内細菌が異なることで胆汁酸の組成も大きく異なること、特定の胆汁酸の生成には特定の菌が関与していること、更に宿主の免疫系に関与する胆汁酸分子種を生成する菌が明らかになることで、腸内細菌による胆汁酸を介した免疫系の制御が可能となり、臨床の領域への応用が期待できる。

Research Products

• [Journal Article] Endocytosis of commensal antigens by intestinal epithelial cells regulates mucosal T cell homeostasis (2019)
  • Author(s): Ladinsky MS、Araujo LP、Zhang X、Veltri J、Galan-Diez M、Soualhi S、Lee C、Irie K、Pinker EY、Narushima S、Bandyopadhyay S、Nagayama M、Elhenawy W、Coombes BK、Ferraris RP、Honda K、Iliev ID、Gao N、Bjorkman PJ、Ivanov II.
  • Journal Title: Science Volume: 363 Issue: 6431
  • DOI: 10.1126/science.aat4042
• [Journal Article] A defined commensal consortium elicits CD8 T cells and anti-cancer immunity (2019)
  • Author(s): T.Tanoue, S.Morita, D.R.Plichta, A.N.Skelly, W.Suda, Y.Sugiura, S.Narushima, H.Vlamakis, I.Motoo, K.Sugita, A.Shiota, K.Takeshita, K.Yasuma, D.Riethmacher, T.Kaisho, J.M.Norman, D.Mucida, M.Suematsu, T.Yaguchi, V.Bucci, T.Inoue, Y.Kawakami, B.Olle, B.Roberts, M.Hattori, R.J.Xavier, K.Atarashi, K.Honda
  • Journal Title: Nature Volume: 565 Issue: 7741 Pages: 600-605
  • DOI: 10.1038/s41586-019-0878-z
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Gut pathobionts underlie intestinal barrier dysfunction and liver T helper 17 cell immune response in primary sclerosing cholangitis. (2019)
  • Author(s): Nakamoto N, Sasaki N, Aoki R, Miyamoto K, Suda W, Teratani T, Suzuki T, Koda Y, Chu PS, Taniki N, Yamaguchi A, Kanamori M, Kamada N, Hattori M, Ashida H, Sakamoto M, Atarashi K, Narushima S, Yoshimura A, Honda K, Sato T, Kanai T.
  • Journal Title: Nat Microbiol. Volume: 4 Issue: 3 Pages: 492-503
  • DOI: 10.1038/s41564-018-0333-1
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] 便中胆汁酸分画濃度年齢別参考値作成のための基礎的検討 (2018)
  • Author(s): 武井一、成高中之、飯田隆、村井毅、黒澤隆夫、山城雄一郎、成島聖子、入戸野博
  • Organizer: 第40会胆汁酸研究会