腸肝指向性腸内細菌と肝臓内免疫応答を介した原発性硬化性胆管炎の進展機序の解明

Material type: 文書・図像類

Author: 中本, 伸宏ほか

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Publication date: 2018

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Note (General)：: type:textPSC患者由来糞便微生物を無菌マウスに移入したヒトフローラ化マウス (PSCUCマウス) において肝臓内TH17細胞の増加を認め、同マウスの腸間膜リンパ節からKlebsiella pneumonia (KP)、Proteus mirabilis (PM)、Enterococcus ...

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科研費研究者番号 : 40383749

科研費研究者番号 : 20590847

科研費研究者番号 : 80435677

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Material Type: 文書・図像類
Title: 腸肝指向性腸内細菌と肝臓内免疫応答を介した原発性硬化性胆管炎の進展機序の解明
Author/Editor: 中本, 伸宏
須田, 亙
福田, 真嗣
褚, 柏松
谷木, 信仁
寺谷, 俊昭
Author Heading: 中本, 伸宏
須田, 亙
福田, 真嗣
褚, 柏松
谷木, 信仁
寺谷, 俊昭
Publication Date: 2018
Publication Date (W3CDTF): 2018
Alternative Title: チョウカンシコウセイチョウナイサイキントカンゾウナイメンエキオウトウオカイシタゲンパツセイコウカセイタンカンエンノシンテンキジョノカイメイ
Chōkan shikōsei chōnai saikin to kanzōnai men'eki ōtō o kaishita genpatsusei kōkasei tankan'en no shinten kijo no kaimei
Role of gut microbiota in the pathogenesis of primary sclerosing cholangitis
Periodical title: 科学研究費補助金研究成果報告書
Text Language Code: jpn
eng
Subject Heading: 原発性硬化性胆管炎,腸内細菌
Target Audience: 一般
Note (General): type:text
PSC患者由来糞便微生物を無菌マウスに移入したヒトフローラ化マウス (PSCUCマウス) において肝臓内TH17細胞の増加を認め、同マウスの腸間膜リンパ節からKlebsiella pneumonia (KP)、Proteus mirabilis (PM)、Enterococcus gallinarum (EG) のbacterial translocation (BT) 誘導菌3菌を分離した。定量PCRの結果、上記BT誘導菌はPSC患者の糞便中に高率に検出され (PSC/UC患者18名中17名で検出)、腸管病変を有するPSCの診断マーカー、および治療標的として有用である可能性が示唆された。 Primary sclerosing cholangitis (PSC) is a chronic inflammatory liver disease and its frequent complication with ulcerative colitis highlights the pathogenic role of epithelial barrier dysfunction. Intestinal barrier dysfunction has been implicated in the pathogenesis of PSC, yet its underlying mechanism remains unknown. Here, we identify Klebsiella pneumonia in the microbiota of PSC patients and demonstrate that K. pneumoniae disrupts the epithelial barrier to initiate bacterial translocation and liver inflammatory responses. Gnotobiotic mice inoculated with PSC-derived microbiota exhibited T helper (Th) 17 cell responses in the live . Bacterial culture of mesenteric lymph nodes in these mice isolated K. pneumoniae, Proteus mirabilis, and Enterococcus gallinarum, which were prevalently detected in PSC patients. These results highlight the role of pathobionts in intestinal barrier dysfunction and liver inflammation, providing insights into therapeutic strategies for PSC.
研究種目 : 基盤研究 (C) (一般) 研究期間 : 2016～2018 課題番号 : 16K09374 研究分野 : 消化器内科
Access Restrictions: 限定公開
Related Material: 科研費研究者番号 : 40383749
科研費研究者番号 : 20590847
科研費研究者番号 : 80435677
Data Provider (Database): 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）
https://irdb.nii.ac.jp
Original Data Provider (Database): 慶應義塾大学 : 慶應義塾大学学術情報リポジトリ