腸内細菌とその遺伝子によるヒト微生物の薬物代謝のマッピング
Michael Zimmermann1, Maria Zimmermann-Kogadeeva1, Rebekka Wegmann1,2
1Department of Microbial Pathogenesis and Microbial Sciences Institute, Yale University School of Medicine, New Haven, CT, USA.
Nature
|June 4, 2019
まとめ
ヒトの腸内微生物群は 薬物の代謝を大きく変化させます 微生物酵素は多くの薬剤を改変し,薬剤反応の個別の違いを説明し,医療療法に影響を与えます.
科学分野:
- 微生物学
- 薬理学について
- メタボロミクス
背景:
- 個々の薬物反応は大きく変化し,副作用や治療の非効率性が生じます.
- 腸内微生物群は,この多様性の要因としてますます認識されていますが,基礎となる分子機構は十分に理解されていません.
研究 の 目的:
- ヒトの腸内細菌が口服薬を代謝する能力を調査する.
- 薬物の代謝に関与する微生物の遺伝子産物を見極める
- 微生物群にコードされた酵素が全身の薬物の代謝に与える影響を決定する.
主な方法:
- ヒトの腸内細菌種76種を 271種類の薬物を代謝する能力で検出した
- 薬物を代謝する微生物酵素を特定するために,高通量遺伝分析と質量スペクトロメトリを用いた.
- マウスモデルにおける薬物の代謝に対する微生物群酵素の影響を評価した.
主要な成果:
- 経口投与される多くの薬はヒトの腸内微生物によって 化学的に変化します
- 薬物の代謝における鍵となる要素として,微生物群にコード化された酵素が特定されました.
- これらの微生物酵素は,腸内および全身の薬物代謝をインビボで大きく影響する.
- 微生物のゲノムコンテンツは 腸内コミュニティの薬物代謝活動を予測できます
結論:
- 腸内微生物群の遺伝子含有量と薬物の代謝の間の直接的な因果関係を確立した.
- 個々の微生物の組成に基づく薬物反応の個別的変動を説明する.
- 薬剤の有効性と安全性における微生物群の重要性を強調し,薬剤開発とパーソナライズド医療への影響を指摘する.
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