論文 - 詳細
| RRC ID | 60620 |
|---|---|
| 著者 | Nakamoto N, Sasaki N, Aoki R, Miyamoto K, Suda W, Teratani T, Suzuki T, Koda Y, Chu PS, Taniki N, Yamaguchi A, Kanamori M, Kamada N, Hattori M, Ashida H, Sakamoto M, Atarashi K, Narushima S, Yoshimura A, Honda K, Sato T, Kanai T. |
| タイトル | Gut pathobionts underlie intestinal barrier dysfunction and liver T helper 17 cell immune response in primary sclerosing cholangitis. |
| ジャーナル | Nat Microbiol |
| Abstract |
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 patients with PSC 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 17 (TH17) cell responses in the liver and increased susceptibility to hepatobiliary injuries. Bacterial culture of mesenteric lymph nodes in these mice isolated K. pneumoniae, Proteus mirabilis and Enterococcus gallinarum, which were prevalently detected in patients with PSC. A bacterial-organoid co-culture system visualized the epithelial-damaging effect of PSC-derived K. pneumoniae that was associated with bacterial translocation and susceptibility to TH17-mediated hepatobiliary injuries. We also show that antibiotic treatment ameliorated the TH17 immune response induced by PSC-derived microbiota. These results highlight the role of pathobionts in intestinal barrier dysfunction and liver inflammation, providing insights into therapeutic strategies for PSC. |
| 巻・号 | 4(3) |
| ページ | 492-503 |
| 公開日 | 2019-3-1 |
| DOI | 10.1038/s41564-018-0333-1 |
| PII | 10.1038/s41564-018-0333-1 |
| PMID | 30643240 |
| MeSH | Adult Aged Animals Bacterial Translocation Cholangitis, Sclerosing / immunology* Cholangitis, Sclerosing / microbiology Colitis, Ulcerative / complications Enterococcus / isolation & purification Epithelial Cells / microbiology Epithelial Cells / pathology Female Gastrointestinal Microbiome* Germ-Free Life Humans Intestines / immunology Intestines / pathology* Klebsiella pneumoniae / isolation & purification Klebsiella pneumoniae / pathogenicity* Liver / immunology* Liver / pathology Lymph Nodes / microbiology Male Mice Mice, Inbred C57BL Middle Aged Organoids / microbiology Proteus mirabilis / isolation & purification Th17 Cells / immunology* |
| IF | 14.633 |
| 引用数 | 34 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 69 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 一般微生物 | JCM1662 JCM1663 JCM1664 JCM20034 JCM20348 JCM20507 JCM20694 |