Lactococcus formosensisとその代謝産物である4-アセタミドブタノ酸によるカスパース-11依存性髄膜神経炎が,治療不可能な機能性便秘に起因する

Xiaoqian Dong¹, Mengshi Chen², Haifeng Liu³

¹Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin, China; School of Medicine, Nankai University, Tianjin, China.

Microbiological research

|September 5, 2025

まとめ

新種の細菌であるLactococcus formosensisは,腸内ニューロンを傷つけることで,難解な機能性便秘 (IFC) に寄与する. この発見はこの困難な状態の診断と治療に新たな道を開きます

科学分野:

胃腸内科
微生物学
神経科学

背景:

収縮性機能性便秘 (IFC) は,治療に遅い経路と耐性があるため,重大な臨床的課題です.
IFCの病原性における特定の腸内微生物の役割は,まだ完全に理解されていません.

研究の目的:

IFCで腸の運動障害に寄与する新しい微生物を特定する.
これらの微生物が腸内神経系 (ENS) に影響するメカニズムを解明する.

主な方法:

IFC患者と健康な対照群の結腸粘膜の分析
ラクトコッカス・フォロメンス (Lf) とその代謝産物をマウスモデルで用いたin vitroおよびin vivo試験
関連する分子経路を特定するためにRNAシーケンシングとメタボロミックプロファイリングを行います.

主要な成果:

Lactococcus formosensis (Lf) のコロニゼーションはIFC患者で増加し,特に興奮性ChAT+ニューロンにおいて,筋腸神経細胞喪失および熱死と相関していた.
Lfとその上位成分は,カスパース-1の活性化により,チャット+ニューロンの熱滅亡を誘導することで,マウスの腸の運動性を低下させた.
Lfによって生成される代謝物4 - アセタミドブタノ酸 (4- ABA) は,カスパーゼ11に依存する経路を通じて,チャット+ニューロン発火を引き起こした.

結論:

Lactococcus formosensisは,不治の機能性便秘における腸の運動機能不全の新たな要因である.
Lf誘発のニューロン発火は,4-ABAとカスパース-11によって媒介され,IFCにおける重要な病原性メカニズムを表しています.
これらの発見は,IFCの微生物群を標的とした診断と治療の開発の基礎となる.

キーワード:

腸内微生物群腸の運動性収縮性機能性便秘腸内ニューロンピロプトーシス

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