Screening for gut microbiota-derived metabolites that activate bitter taste receptors

• Project/Area Number: 15K15047
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: General pharmacology
• Research Institution: The University of Tokyo
• Principal Investigator: Morita Hiroyuki 東京大学, 医学部附属病院, 講師 (60323573)
• Co-Investigator(Kenkyū-buntansha): IKEDA Yuichi 東京大学, 医学部附属病院, 特任准教授 (10744419) ; KUMAGAI Hidetoshi 東京大学, 医学部附属病院, 特任助教 (20281008)
• Project Period (FY): 2015-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2015: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
• Keywords: 苦味受容体 / Gタンパク質共役型受容体 / 常在性腸内細菌叢 / 低分子代謝産物

Outline of Final Research Achievements

This study is being conducted to identify gut microbiota-derived metabolites that activate bitter taste receptors expressed in host intestinal epithelium. Utilizing the salicin-T2R16 axis as a model, we first established a novel assay system for this purpose. HEK293T cells transiently transfected with T2R16, G16/gust44 and NFAT-luciferase reporter were stimulated with salicin. Dose-dependent activation of NFAT-reporter was successfully observed, suggesting that this assay system can be applied to other bitter taste receptors. The actual metabolite screening using this assay is currently in progress.

Research Products

• [Journal Article] Quantitative measurement of GPCR endocytosis via pulse-chase covalent labeling (2015)
  • Author(s): Kumagai H, Ikeda Y, Motozawa Y, Fujishiro M, Okamura T, Fujio K, Okazaki H, Nomura S, Takeda N, Harada M, Toko H, Takimoto E, Akazawa H, Morita H, Suzuki J, Yamazaki T, Yamamoto K, Komuro I, Yanagisawa M
  • Journal Title: PLoS One Volume: 10 Issue: 5 Pages: e0129394-e0129394
  • DOI: 10.1371/journal.pone.0129394
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Monitoring beta-arrestin recruitment via beta-lactamase enzyme fragment complementation: purification of peptide E as a low-affinity ligand for mammalian bombesin receptors (2015)
  • Author(s): Ikeda Y*, Kumagai H*, Okazaki H, Fujishiro M, Motozawa Y, Nomura S, Takeda N, Toko H, Takimoto E, Akazawa H, Morita H, Suzuki J, Yamazaki T, Komuro I, Yanagisawa M (co-first author)
  • Journal Title: PLoS One Volume: 10 Issue: 6 Pages: e0127445-e0127445
  • DOI: 10.1371/journal.pone.0127445
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] A food-derived flavonoid luteolin protects against angiotensin II-induced cardiac remodeling (2015)
  • Author(s): Nakayama A, Morita H, Nakao T, Yamaguchi T, Sumida T, Ikeda Y, Kumagai H, Motozawa Y, Takahashi T, Imaizumi A, Hashimoto T, Nagai R, Komuro I
  • Journal Title: PLoS One Volume: 10 Issue: 9 Pages: e0137106-e0137106
  • DOI: 10.1371/journal.pone.0137106
  • Peer Reviewed / Open Access