微生物群によって調節される代謝物は,NLRP6炎症体シグナリングを調節することによって腸内微環境を形成する
Maayan Levy1, Christoph A Thaiss1, David Zeevi2
1Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel.
Cell
|December 7, 2015
まとめ
タウリン,ヒスタミン,精子などの微生物代謝物は,NLRP6炎症体と抗微生物ペプチド (AMP) を調節することによって,腸内免疫を調節する. このバランスを取り戻すことで 腸炎や腸不全が治ります
科学分野:
- 微生物学
- 免疫学
- 胃腸内科
背景:
- ホストと微生物の共進化は 腸内ホメオスタシスと疾患に不可欠です
- 腸内微環境の調節原理,特に炎症性の関与は完全に理解されていません.
- 炎症体活性と腸内免疫を調節する特定の微生物代謝物は不明である.
研究 の 目的:
- 宿主-微生物群のインターフェイスを調節する微生物代謝物を特定する.
- これらの代謝物が炎症体シグナル伝達と抗微生物ペプチド (AMP) プロフィールに影響を与えるメカニズムを解明する.
- 腸内微生物群の安定性を維持する この軸の役割と 腸内微生物群の安定性を維持する この軸の役割と 腸内微生物群の安定性を維持する この軸の役割と 腸内微生物群の安定性を維持する この軸の役割と 腸内微生物群の安定性を維持する この軸の役割と 腸内微生物群の安定性を維持する
主な方法:
- NLRP6炎症体シグナル伝達における微生物代謝物 (タウリン,ヒスタミン,精子) の役割を調査した.
- 炎症体の活性が上皮のIL-18分泌と下流の抗菌ペプチド (AMP) プロファイルに与える影響を評価した.
- ディスバイオシスの発達と大腸炎における治療的介入を研究するために,糞便の微生物移植モデルを使用した.
主要な成果:
- 微生物と関連した代謝物 (タウリン,ヒスタミン,精子) は,NLRP6炎症体と上皮のIL-18分泌の主要な調節物として特定されました.
- インフラマソームの欠乏は,AMPの歪みをもたらし,ディスバイオシスを促進しました.
- 大腸炎を誘発する微生物群は,代謝物を通して炎症性の活性を抑制し,AMPのバランスを変化させ,その植民を促した.
- メタボリート-炎症体-AMP軸の回復は 大腸炎を緩和し 腸内微生物群を正常化させました
結論:
- 微生物の代謝物は,先天的な免疫調節を通して宿主-微生物のインターフェースを形成する上で重要な役割を果たします.
- 特定されたメタボリート-炎症体-AMP軸は,微生物コミュニティの安定性を維持するために不可欠です.
- 標的化された代謝干渉 (ポストバイオティクス) は,ディスバイオシス関連疾患の治療または予防に有望である.
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