Studies on TTX loop in marine ecosystem - an enigma of missing links among TTX-bearing organisms

• Project/Area Number: 15H04552
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Aquatic life science
• Research Institution: Nihon University
• Principal Investigator: ITOI Shiro 日本大学, 生物資源科学部, 准教授 (30385992)
• Co-Investigator(Kenkyū-buntansha): 杉田 治男 日本大学, 生物資源科学部, 教授 (50139052) ; 鈴木 美和 日本大学, 生物資源科学部, 准教授 (70409069) ; 高谷 智裕 長崎大学, 水産・環境科学総合研究科(水産), 教授 (90304972)
• Project Period (FY): 2015-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥16,900,000 (Direct Cost: ¥13,000,000、Indirect Cost: ¥3,900,000); Fiscal Year 2018: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000); Fiscal Year 2017: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000); Fiscal Year 2016: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2015: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
• Keywords: フグ毒 / テトロドトキシン / TTXループ / オオツノヒラムシ / ツノヒラムシ属 / TTX / クサフグ / 食物連鎖（食物網） / ヒラムシ / トラフグ / フグ毒ループ

Outline of Final Research Achievements

We revealed the presence of numerous Takifugu pardalis eggs in the intestinal contents of another pufferfish, Takifugu niphobles, suggesting that T. niphobles ingested the toxic eggs of another pufferfish T. pardalis to toxify themselves more efficiently. Additionally, the toxic goby Yongeichthys criniger and the milkspotted pufferfish Chelonodon patoca fed on the toxic flatworm Planocera multitentaculata. These results suggest that concentrated TTX is pooled in the TTX loop among the TTX-bearing organisms, which are the predators at higher trophic levels in the food web.

Academic Significance and Societal Importance of the Research Achievements

これまでフグ毒は、細菌を生産者とする食物連鎖（網）を通じてフグの体内に蓄積されると考えられていた。一方、細菌が生産するフグ毒の量が少ないことから、フグが持つ毒量を説明できないとの指摘があった。本研究の成果は、フグ毒を保有する高次捕食者間でフグ毒をやり取りしている事例を複数報告し、フグ毒がこれら高次捕食者間で循環していることを提案した。本研究の成果は、未解明な部分が多く残されていたフグの毒化機構に新たな考え方を導入することが期待される。

Research Products

• [Journal Article] Role of maternal tetrodotoxin in survival of larval pufferfish (2018)
  • Author(s): Itoi Shiro、Suzuki Miwa、Asahina Kiyoshi、Sawayama Eitaro、Nishikubo Junki、Oyama Hikaru、Takei Mitsuki、Shiibashi Nanae、Takatani Tomohiro、Arakawa Osamu、Sugita Haruo
  • Journal Title: Toxicon Volume: 148 Pages: 95-100
  • DOI: 10.1016/j.toxicon.2018.04.014
  • Peer Reviewed
• [Journal Article] Including planocerid flatworms in the diet effectively toxifies the pufferfish, Takifugu niphobles (2018)
  • Author(s): Itoi Shiro、Ueda Hiroyuki、Yamada Riko、Takei Mitsuki、Sato Tatsunori、Oshikiri Shotaro、Wajima Yoshiki、Ogata Ryuya、Oyama Hikaru、Shitto Takahiro、Okuhara Kazuya、Tsunashima Tadasuke、Sawayama Eitaro、Sugita Haruo
  • Journal Title: Scientific Reports Volume: 8 Issue: 1 Pages: 12302-12302
  • DOI: 10.1038/s41598-018-30696-z
  • Peer Reviewed / Open Access
• [Journal Article] Maturation-associated changes in internal distribution and intra-ovarian microdistribution of tetrodotoxin in the pufferfish Takifugu pardalis (2018)
  • Author(s): Gao Wei、Kanahara Yoko、Tatsuno Ryohei、Soyano Kiyoshi、Nishihara Gregory N.、Urata Chisato、Takatani Tomohiro、Arakawa Osamu
  • Journal Title: Fisheries Science Volume: 84 Issue: 4 Pages: 723-732
  • DOI: 10.1007/s12562-018-1209-2
  • NAID: 40021587964
  • Peer Reviewed
• [Journal Article] Stellatolide H, a cytotoxic peptide lactone from a deep-sea sponge Discodermia sp. (2018)
  • Author(s): Nakamukai Shohei、Takada Kentaro、Furihata Kazuo、Ise Yuji、Okada Shigeru、Morii Yasuhiro、Yamawaki Nobuhiro、Takatani Tomohiro、Arakawa Osamu、Gustafson Kirk R.、Matsunaga Shigeki
  • Journal Title: Tetrahedron Letters Volume: 59 Issue: 26 Pages: 2532-2536
  • DOI: 10.1016/j.tetlet.2018.05.033
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] フグ毒TTXの生物学的意義を通してフグにおけるTTXの獲得機構を探る (2018)
  • Author(s): 糸井史朗
  • Journal Title: アグリバイオ Volume: 2 Pages: 397-399
  • NAID: 40021808250
• [Journal Article] テトロドトキシンの生物学的意義とフグ毒中毒 (2018)
  • Author(s): 糸井史朗
  • Journal Title: モダンメディア Volume: 64 Pages: 241-249
  • Open Access
• [Journal Article] TTX-bearing planocerid flatworm (Platyhelminthes: Acotylea) in the Ryukyu Islands, Japan (2018)
  • Author(s): Ueda H, Itoi S, Sugita H
  • Journal Title: Marine Drugs Volume: 16 Issue: 1 Pages: 37-37
  • DOI: 10.3390/md16010037
  • Peer Reviewed / Open Access
• [Journal Article] A molecular framework for the taxonomy and systematics of Japanese marine turbellarian flatworms (Platyhelminthes, Polycladida) (2017)
  • Author(s): Tsunashima T, Hagiya M, Yamada R, Koito T, Tsuyuki N, Izawa S, Kosoba K, Itoi S, Sugita H
  • Journal Title: Aquatic Biology Volume: 26 Pages: 159-167
  • DOI: 10.3354/ab00682
  • Peer Reviewed / Open Access
• [Journal Article] Toxins of Pufferfish?Distribution, Accumulation Mechanism, and Physiologic Functions (2017)
  • Author(s): Arakawa Osamu、Takatani Tomohiro、Taniyama Shigeto、Tatsuno Ryohei
  • Journal Title: Aqua-BioScience Monographs Volume: 10 Issue: 3 Pages: 41-80
  • DOI: 10.5047/absm.2017.01003.0041
  • NAID: 40021574438
  • Peer Reviewed / Open Access
• [Journal Article] Seasonal changes in the tetrodotoxin content of the flatworm Planocera multitentaculata (2017)
  • Author(s): Yamada R, Tsunashima T, Takei M, Sato T, Wajima Y, Kawase M, Oshikiri S, Kajitani Y, Kosoba K, Ueda H, Abe K, Itoi S, Sugita H
  • Journal Title: Marine Drugs Volume: 15 Issue: 3 Pages: 56-56
  • DOI: 10.3390/md15030056
  • Peer Reviewed / Open Access
• [Journal Article] Administration of tetrodotoxin protects artificially-raised juvenile tiger puffer Takifugu rubripes from predators. (2017)
  • Author(s): Sakakura, Y., Takatani, T., Nakayasu, J., Yamazaki, H., Sakiyama, K.
  • Journal Title: Fisheries Science Volume: 83 Issue: 2 Pages: 191-198
  • DOI: 10.1007/s12562-016-1046-0
  • NAID: 120006987423
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Transcriptome analysis of tetrodotoxin sensing and action of tetrodotoxin in central nervous system of tiger puffer Takifugu rubripes juveniles (2017)
  • Author(s): Okita, K., Tan, E., Satone, H., Kinoshita, S., Asakawa, S., Ojima, D., Yamazaki, H., Sakiyama, K., Takatani, T., Arakawa, O., Hagiwara, A., Sakakura, Y.
  • Journal Title: Fisheries Science Volume: 83 Issue: 3 Pages: 401-412
  • DOI: 10.1007/s12562-017-1079-z
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Seasonal changes in the tetrodotoxin content of the pufferfish Takifugu niphobles (2016)
  • Author(s): Itoi S, Ishizuka K, Mitsuoka R, Takimoto N, Yokoyama N, Detake A, Takayanagi C, Yoshikawa S, Sugita H
  • Journal Title: Toxicon Volume: 114 Pages: 53-58
  • DOI: 10.1016/j.toxicon.2016.02.020
  • Peer Reviewed
• [Journal Article] Growth and paralytic shellfish toxin production by the dinoflagellate Alexandrium catenella cultured under monochromatic light (2016)
  • Author(s): Jiang S, Iwashita H, Arakawa O, Takatani T
  • Journal Title: Aquaculture Science Volume: 64 Pages: 379-390
  • NAID: 130006258900
  • Peer Reviewed
• [Journal Article] Toxic Takifugu pardalis eggs found in T. niphobles gut: implications for TTX accumulation in the pufferfish (2015)
  • Author(s): Itoi S, Kozaki A, Komori K, Tsunashima T, Noguchi S, Kawane M, Sugita H
  • Journal Title: Toxicon Volume: 108 Pages: 141-146
  • DOI: 10.1016/j.toxicon.2015.10.009
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] TTX保有生物におけるTTXの獲得ルートと役割 (2019)
  • Author(s): 糸井史朗
  • Organizer: マリンケミカルバイオロジー研究会2019
  • Invited
• [Presentation] フグ毒テトロドトキシンを保有するヒラムシの消化管のメタゲノム解析 (2019)
  • Author(s): 米澤 遼、五十嵐洋治、吉武和敏、木下滋晴、糸井史朗、杉田治男、浅川修一
  • Organizer: 平成31年度日本水産学会春季大会
• [Presentation] フグ毒テトロドトキシンを保有するヒラムシのミトコンドリアゲノムの解読 (2019)
  • Author(s): 米澤 遼、五十嵐洋治、吉武和敏、木下滋晴、糸井史朗、杉田治男、横堀伸一、浅川修一
  • Organizer: 平成31年度日本水産学会春季大会
• [Presentation] トラフグ属魚類の毒化に関わるオオツノヒラムシの影響 (2018)
  • Author(s): 糸井史朗、尾山 輝、杉田治男
  • Organizer: 日本水産増殖学会第17回大会
• [Presentation] オオツノヒラムシの産卵期におけるTTX保有量の変動 (2018)
  • Author(s): 吉敷綾乃、上田紘之、糸井史朗、杉田治男
  • Organizer: 平成30年度日本水産学会秋季大会
• [Presentation] フグはフグ毒をどこから獲得し、何に使うのか？ (2018)
  • Author(s): 糸井史朗
  • Organizer: 第63回日本放線菌学会学術講演会
  • Invited
• [Presentation] フグ毒検査法における抽出操作の簡素化とHPLC-FL分析の有効性 (2018)
  • Author(s): 谷口香織、高尾秀樹、阿部敬子、辰野竜平、Gregoly N. Nishihara、阪倉良孝、高谷智裕、荒川修
  • Organizer: 日本食品衛生学会
• [Presentation] 海産フグと淡水フグのTTX/PST蓄積能 (2018)
  • Author(s): 山田美紗子、金原葉子、高威、土井啓行、吉川廣幸、辰野竜平、長島裕二、高谷智裕、荒川修
  • Organizer: 日本食品衛生学会
• [Presentation] フグ毒添加飼料がトラフグ稚魚の成長に与える影響 (2018)
  • Author(s): 阪倉良孝、佐藤はるか、天野勝文、高谷智裕
  • Organizer: 平成30年度日本水産学会春季大会
• [Presentation] トラフグ初期発育段階におけるフグ毒の獲得 (2018)
  • Author(s): 佐々木杜汰、寺島武寿、沖田光玄、平井慈恵、高谷智裕、荒川 修
  • Organizer: 平成30年度日本水産学会春季大会
• [Presentation] 窒素安定同位体を用いた紅藻マクリの培養 (2017)
  • Author(s): 姜 珊珊、桑野和可、Gregory N. Nishihara、浦田千里、下田隆介、高谷智裕、荒川 修
  • Organizer: 平成29年度日本水産学会春季大会
  • Place of Presentation: 東京海洋大学（東京都品川区）
  • Year and Date: 2017-03-29
• [Presentation] 屋久島および石垣島産オウギガニ科カニ類の毒性プロファイル (2017)
  • Author(s): 宗宮史樹、高谷智裕、青島 隆、森井康宏、荒川 修
  • Organizer: 平成29年度日本水産学会春季大会
  • Place of Presentation: 東京海洋大学（東京都品川区）
  • Year and Date: 2017-03-28
• [Presentation] オオツノヒラムシを中心とする環境中におけるTTXの動態 (2017)
  • Author(s): 山田理子、武井美月、和嶋良己、糸井史朗、杉田治男
  • Organizer: 平成29年度日本水産学会春季大会
  • Place of Presentation: 東京海洋大学（東京都品川区）
  • Year and Date: 2017-03-27
• [Presentation] Toxification process of Takifugu pufferfish: detection of TTX-bearing organisms in intestinal contents of pufferfish (2017)
  • Author(s): Itoi S, Takei M, Yamada R, Sugita H
  • Organizer: JSFS 85th Anniversary-Commemorative International Symposium “Fisheries Science for Future Generations”
  • Int'l Joint Research
• [Presentation] Effects of sexual maturation on the toxicity of the toxic flatworm Planocera multitentaculata (2017)
  • Author(s): Ueda H, Yamada R, Takei M, Abe M, Itoi S, Sugita H
  • Organizer: JSFS 85th Anniversary-Commemorative International Symposium “Fisheries Science for Future Generations”
  • Int'l Joint Research
• [Presentation] Tetrodotoxin-specific toxin uptake and maturation-associated toxin accumulation in the pufferfish Takifugu pardalis. (2017)
  • Author(s): Gao W, Kanahara Y, Tatsuno R, Yoshikawa H, Soyano K, Takatani T, Arakawa O
  • Organizer: JSFS 85th Anniversary-Commemorative International Symposium “Fisheries Science for Future Generations”
  • Int'l Joint Research
• [Presentation] Tetrodotoxin dynamics in the pufferfish Takifugu rubripes changes depending of its liver development (2017)
  • Author(s): Tatsuno R, Gao W, Yoshikawa H, Takahashi H, Fukuda T, Furushita M, Nishihara GN, Takatani T, Arakawa O
  • Organizer: JSFS 85th Anniversary-Commemorative International Symposium “Fisheries Science for Future Generations”
  • Int'l Joint Research
• [Presentation] Seasonal changes in TTX content of the toxic flatworm Planocera multitentaculata (2016)
  • Author(s): Riko Yamada, Tadasuke Tsunashima, Yusuke Kajitani, Shiro Itoi, Haruo Sugita
  • Organizer: The joint meeting of the 22nd International Congress of Zoology and the 87th Meeting of the Zoological Society of Japan
  • Place of Presentation: 沖縄コンベンションセンター（沖縄県宜野湾市）
  • Year and Date: 2016-11-17
  • Int'l Joint Research
• [Presentation] オオツノヒラムシにおけるTTX保有量の季節変化 (2016)
  • Author(s): 山田理子、綱島忠相、梶谷雄介、糸井史朗、杉田治男
  • Organizer: 平成28年度日本水産学会秋季大会
  • Place of Presentation: 近畿大学農学部（奈良県奈良市）
  • Year and Date: 2016-09-09
• [Presentation] 有毒Planocera属ヒラムシ摂餌によるクサフグの毒化 (2016)
  • Author(s): 武井美月、出頭孝浩、山田理子、糸井史朗、杉田治男
  • Organizer: 平成28年度日本水産学会秋季大会
  • Place of Presentation: 近畿大学農学部（奈良県奈良市）
  • Year and Date: 2016-09-09
• [Presentation] Providing pufferfish liver for human consumption (1): Toxicity evaluation (2016)
  • Author(s): Taniguchi K, Takao H, Onuki K, Tatsuno R, Sakakura Y, Takatani T, Arakawa O, Noguchi T
  • Organizer: The 7th World Fisheries Congress in Busan, Korea
  • Place of Presentation: Busan, Korea
  • Year and Date: 2016-05-23
  • Int'l Joint Research
• [Presentation] Growth and PSP production of the toxic dinoflagellate Alexandrium catenella cultured under monowavelength light irradiation (2016)
  • Author(s): Jiang S, Iwashita H, Arakawa O, Takatani T
  • Organizer: The 7th World Fisheries Congress in Busan, Korea
  • Place of Presentation: Busan, Korea
  • Year and Date: 2016-05-23
  • Int'l Joint Research
• [Presentation] Toxification of the larval pufferfish Takifugu niphobles by the larval flatworm Planocera multitentaculata (2016)
  • Author(s): Riko Yamada, Tadasuke Tsunashima, Kazuya Okuhara, Shiro Itoi, Haruo Sugita
  • Organizer: The 7th World Fisheries Congress in Busan, Korea
  • Place of Presentation: Busan, Korea
  • Year and Date: 2016-05-23
  • Int'l Joint Research
• [Presentation] Toxification of the Takifugu pufferfish via a TTX loop consisting of TTX-bearing organisms (2016)
  • Author(s): Shiro Itoi, Ao Kozaki, Keitaro Komori, Tadasuke Tsunashima, Shunsuke Noguchi, Mitsuo Kawane, Haruo Sugita
  • Organizer: The 7th World Fisheries Congress in Busan, Korea
  • Place of Presentation: Busan, Korea
  • Year and Date: 2016-05-23
  • Int'l Joint Research
• [Presentation] 分子生物学的手法による有毒ヒラムシPlanocera属の検出法の開発 (2016)
  • Author(s): 山田理子・綱島忠相・梶谷雄介・糸井史朗・杉田治男
  • Organizer: 平成28年度日本水産学会春季大会
  • Place of Presentation: 東京海洋大学（東京都品川区）
  • Year and Date: 2016-03-29
• [Presentation] ミトコンドリアゲノムコードのCOI遺伝子領域に基づく多岐腸類の分子系統解析 (2016)
  • Author(s): 綱島忠相・山田理子・梶谷雄介・萩谷盛雄・糸井史朗・杉田治男
  • Organizer: 平成28年度日本水産学会春季大会
  • Place of Presentation: 東京海洋大学（東京都品川区）
  • Year and Date: 2016-03-27
• [Presentation] Planocera属幼生がクサフグ稚魚の毒化に及ぼす影響 (2015)
  • Author(s): 山田理子・綱島忠相・奥原和也・糸井史朗・杉田治男
  • Organizer: 平成27年度日本水産学会秋季大会
  • Place of Presentation: 東北大学（仙台市）
  • Year and Date: 2015-09-23
• [Presentation] TTXを保有するヒラムシ類の系統学的地位および保有毒量の経年変化 (2015)
  • Author(s): 綱島忠相・山田理子・萩谷盛雄・梶谷雄介・糸井史朗・杉田治男
  • Organizer: 平成27年度日本水産学会秋季大会
  • Place of Presentation: 東北大学（仙台市）
  • Year and Date: 2015-09-23
• [Presentation] 交雑フグの毒性 (2015)
  • Author(s): 高谷智裕・鈴木重則・望岡典隆・荒川修
  • Organizer: 平成27年度日本水産学会秋季大会
  • Place of Presentation: 東北大学（仙台市）
  • Year and Date: 2015-09-22
• [Presentation] Transcriptome Analysis of Tetrodotoxin Sensing and Action of Tetrodotoxin in the Brain of Tiger Puffer Takifugu rubripes by Next-Generation Sequencing (2015)
  • Author(s): Okita K, Satone H, Tan E, Kinoshita S, Asakawa S, Yamazaki H, Sakiyama K, Takatani T, Arakawa O, Hagiwara A, Sakakura Y
  • Organizer: 145th American Fisheries Society Annual Meeting
  • Place of Presentation: Portland, Oregon, USA
  • Year and Date: 2015-08-16
• [Presentation] フグにおけるTTXの生物学的役割 (2015)
  • Author(s): 糸井史朗
  • Organizer: 新学術領域研究「天然物ケミカルバイオロジー」地区ミニシンポジウム
  • Place of Presentation: 名古屋大学野依記念物質科学研究館（愛知県名古屋市）
  • Year and Date: 2015-05-14
  • Invited
• [Remarks] 母親由来の毒がフグの赤ちゃんを守る！
  • URL: http://www.msr-nihon-university.org/2018/05/06/press-release/
• [Remarks] クサフグはヒラムシを食べて効果的に毒化する
  • URL: http://www.msr-nihon-university.org/2018/08/19/press-release-7/
• [Remarks] 糸井史朗准教授のフグ毒に関する研究が読売新聞で紹介されました
  • URL: http://www.msr-nihon-university.org/2019/04/02/
• [Remarks] 分子系統学的手法学的手法にもとづくヒラムシ類の系統分類
  • URL: http://www.msr-nihon-university.org/press-release/20171022-2/
• [Remarks] 琉球列島で採取したフグ毒保有ヒラムシ
  • URL: http://www.msr-nihon-university.org/press-release/20180121-2/
• [Remarks] ヒラムシの生態で新発見 フグの毒化に寄与か
  • URL: http://www.nu-press.net/archives/article003723.html