人間の腸内細菌エゲルテルラ・レンタ (Eggerthella lenta) による心臓薬の不活性化を予測し,操作する
Henry J Haiser1, David B Gootenberg, Kelly Chatman
1Faculty of Arts and Sciences Center for Systems Biology, Harvard University, Cambridge, MA 02138, USA.
Science (New York, N.Y.)
|July 23, 2013
まとめ
腸内細菌エゲルテルラ・レンタは,特定のサイトクロームオペロンを通して,心臓薬ディゴキシンを無効化する. 食事中のタンパク質の摂取は,この微生物の代謝に影響を与え,体内の薬物レベルに影響を与えます.
科学分野:
- 微生物学 微生物学とは
- 薬理学 薬理学とは
- ゲノミクスゲノミクスとは
背景:
- 人間の胃腸微生物群は,薬剤の有効性や毒性に大きな影響を与えます.
- マイクロバイオームと薬物の相互作用の背後にあるメカニズムは,しばしば十分に理解されていません.
研究 の 目的:
- 腸内アクティノバクテリウムエッゲルテルラ・レンタが心臓薬ディゴキシンを無効化するメカニズムを解明する.
- この微生物の薬物の代謝に宿主食の影響を調査する.
主な方法:
- ディゴキシンに曝されたE. lentaの転写プロファイリング.
- 関連する遺伝的要素を特定するための比較ゲノミクス.
- 代謝活性を確認するための培養ベースの測定法.
- グノトビオティックマウスにおける薬理動力学的研究.
主要な成果:
- E. lentaのディゴキシン上調のサイトクロームオペロンは,ディゴキシン不活性化に不可欠であると特定されました.
- このオペロンはアルギニンによって抑制され,代謝しない株では存在しない.
- 食事中のタンパク質は,マウスにおけるディゴキシンの微生物の in vivo 代謝を低下させ,血清および尿中の薬剤濃度を変化させることが示されました.
結論:
- Eggerthella lentaは,サイトクロームオペロンを含むディゴキシン不活性化のための特定のメカニズムを有しています.
- 食事中のタンパク質の摂取は,腸内微生物群によるディゴキシンの体内代謝を調節する.
- 薬理学的アウトカムは,ヒトと微生物のゲノム間の相互作用を考慮する必要があります.
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