ID | 118835 |
著者 |
Kasai, Kaichi
Toyama Prefectural University
Igarashi, Naoya
Toyama Prefectural University
Tada, Yuki
Toyama Prefectural University
Kani, Koudai
Toyama Prefectural University
Takano, Shun
Toyama Prefectural University
Yanagibashi, Tsutomu
Toyama Prefectural Institute for Pharmaceutical Research
Usui-Kawanishi, Fumitake
Toyama Prefectural University
Fujisaka, Shiho
University of Toyama
Watanabe, Shiro
University of Toyama
Takatsu, Kiyoshi
Toyama Prefectural Institute for Pharmaceutical Research
Tobe, Kazuyuki
University of Toyama
Furusawa, Yukihiro
Toyama Prefectural University
Nagai, Yoshinori
Toyama Prefectural University
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キーワード | antibiotic
bile acid
cholic acid
fibrosis
gut microbiota
inflammation
macrophage
metronidazole
non-alcoholic steatohepatitis
vancomycin
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資料タイプ |
学術雑誌論文
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抄録 | The potential roles of the gut microbiota in the pathogenesis of non-alcoholic fatty liver disease, including non-alcoholic steatohepatitis (NASH), have attracted increased interest. We have investigated the links between gut microbiota and NASH development in Tsumura-Suzuki non-obese mice fed a high-fat/cholesterol/cholate-based (iHFC) diet that exhibit advanced liver fibrosis using antibiotic treatments. The administration of vancomycin, which targets Gram-positive organisms, exacerbated the progression of liver damage, steatohepatitis, and fibrosis in iHFC-fed mice, but not in mice fed a normal diet. F4/80+-recruited macrophages were more abundant in the liver of vancomycin-treated iHFC-fed mice. The infiltration of CD11c+-recruited macrophages into the liver, forming hepatic crown-like structures, was enhanced by vancomycin treatment. The co-localization of this macrophage subset with collagen was greatly augmented in the liver of vancomycin-treated iHFC-fed mice. These changes were rarely seen with the administration of metronidazole, which targets anaerobic organisms, in iHFC-fed mice. Finally, the vancomycin treatment dramatically modulated the level and composition of bile acid in iHFC-fed mice. Thus, our data demonstrate that changes in inflammation and fibrosis in the liver by the iHFC diet can be modified by antibiotic-induced changes in gut microbiota and shed light on their roles in the pathogenesis of advanced liver fibrosis.
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掲載誌名 |
International Journal of Molecular Sciences
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ISSN | 14220067
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出版者 | MDPI
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巻 | 24
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号 | 4
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開始ページ | 4050
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発行日 | 2023-02-17
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権利情報 | This article is an open access article distributed under the terms and conditions of the Creative CommonsAttribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
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EDB ID | |
出版社版DOI | |
出版社版URL | |
フルテキストファイル | |
言語 |
eng
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著者版フラグ |
出版社版
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部局 |
医学系
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