レボドパ代謝のための種間腸内細菌経路の発見と抑制

Vayu Maini Rekdal¹, Elizabeth N Bess^2,3,4, Jordan E Bisanz²

¹Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, MA 02138, USA.

Science (New York, N.Y.)

|June 15, 2019

まとめ

腸内微生物群はパーキンソン病薬であるレボドーパ (l-ドーパ) を特定の細菌酵素で代謝する. この代謝を阻害する新薬が発見され,マウスの薬剤の生物利用性を高めました.

科学分野:

微生物学
薬理学について
神経科学

背景:

腸内微生物群は,パーキンソン病の主要な薬であるレボドーパ (l-ドーパ) の代謝に大きく影響します.
この微生物の代謝は薬の有効性を低下させ,副作用を悪化させる可能性がありますが,具体的なメカニズムは不明です.

研究の目的:

腸内微生物群媒介によるレボドパ代謝に関与する細菌,遺伝子,酵素の解明.
レボドパの生物利用性を改善するためにこれらの微生物酵素を阻害する可能性を調査する.

主な方法:

細菌によるレボドパ代謝の種間経路を特徴づけた.
特定された主要酵素: *Enterococcus faecalis* のチロシンデカルボキシラーゼと *Eggerthella lenta* のデヒドロキシラーゼ
宿主標的薬と新しい化合物を用いて微生物のレボドーパ代謝を抑制した.

主要な成果:

レボドーパをドーパミンに,それから*m*チラミンに変換する2段階の経路をE. faecalis*とE. lenta*で説明しました.
微生物のレボドパ代謝に対して無効であることが示された.
パーキンソン病患者の微生物のレボドーパ代謝を阻害し,マウスのレボドーパの生物利用性を高める化合物を特定しました.

結論:

特定された細菌酵素と経路は,腸内でのレボドパ代謝に不可欠です.
宿主酵素ではなく微生物の酵素をターゲットにすることでレボドーパ治療の効果を高める有望な戦略です
新しい阻害剤は,パーキンソン病患者のレボドパの生物利用性を改善する可能性がある.

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