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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
キーワード
antibiotic
bile acid
cholic acid
fibrosis
gut microbiota
inflammation
macrophage
metronidazole
non-alcoholic steatohepatitis
vancomycin
資料タイプ
学術雑誌論文
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.
掲載誌名
International Journal of Molecular Sciences
ISSN
14220067
出版者
MDPI
24
4
開始ページ
4050
発行日
2023-02-17
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/).
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
著者版フラグ
出版社版
部局
医学系