@article{4a6a4e7d15d04f08901c76feb9f31c8d,
title = "Bile acid dysmetabolism in the gut-microbiota-liver axis under hepatitis C virus infection",
abstract = "Background & Aims: We recently analysed and reported the features of the micro biome under hepatitis C virus (HCV) infection, but the effect of HCV infection on bile acid (BA) metabolism in the gut-liver axis remains poorly understood. The aim of this study was to clarify the characteristics of the gut-liver axis in HCV-infected patients. Methods: The faecal BAs composition and gut microbiota from 100 chronic hepatitis C (CHC) patients were compared with those from 23 healthy individuals. For transcriptional analysis of the liver, 22 mild CHC (fibrosis stages [F] 0-2) and 42 advanced CHC (F3-4) cases were compared with 12 healthy individuals. The findings were confirmed using chimeric mice with human hepatocytes infected with HCV HCR6. Results: Chronic hepatitis C patients, even at earlier disease stages, showed BA profiles distinct from healthy individuals, in which faecal deoxycholic acid (DCA) was significantly reduced and lithocholic acid or ursodeoxycholic acid became dominant. The decrease in faecal DCA was correlated with reduction in commensal Clostridiales and increase in oral Lactobacillales. Impaired biosynthesis of cholic acid (CA) was observed as a reduction in the transcription level of cytochrome P450 8B1 (CYP8B1), a key enzyme in CA biosynthesis. The reductions in faecal DCA and liver CYP8B1 were also observed in HCV-infected chimeric mice. Conclusions: Chronic hepatitis C alters the intestinal BA profile, in association with the imbalance of BA biosynthesis, which differs from the pattern in NAFLD. These imbalances appear to drive disease progression through the gut-microbiome-liver axis.",
author = "Takako Inoue and Yui Funatsu and Masaya Ohnishi and Masanori Isogawa and Keigo Kawashima and Masaru Tanaka and Kei Moriya and Hideto Kawaratani and Rie Momoda and Etsuko Iio and Hidewaki Nakagawa and Yutaka Suzuki and Kentaro Matsuura and Kei Fujiwara and Atsushi Nakajima and Hitoshi Yoshiji and Jiro Nakayama and Yasuhito Tanaka",
note = "Funding Information: We thank Center for Advanced Instrumental and Educational Supports, Faculty of Agriculture, Kyushu University, for support with DNA sequencing on the MiSeq sequencer. Additionally, we thank Junichi Yamao, Akira Mitoro, Ryuichi Noguchi, Tadashi Namisaki, Masakazu Uejima, Tsuyoshi Mashitani, Kosuke Takeda, Mitsuteru Kitade, Naotaka Shimozato, Yasushi Okura, Kosuke Kaji, Hiroaki Takaya, Norihisa Nishimura, Yasuhiko Sawada, Shinya Sato, Kenichiro Seki, Soichiro Saikawa, Shintaro Ogawa, Hatsumi Koshiyama and Asami Yamaguchi for their support in collecting faecal samples; we thank all participant patients and healthy individuals for providing samples and personal information. We also thank Dr Michinori Kohara for providing the HCR6 strain, and Dr Kikuko Hotta for providing information on RNA‐Seq in NAFLD patients. This research was supported by AMED under Grant Number JP18fk0210201h0002 and JP20fk0310101h0003, the Ministry of Education, Culture, Sports, Science, and Technology (20K08012), grant support from MSD, grant‐in‐aid from Gilead Sciences and grant‐in‐aid for research from Nagoya City University. Funding Information: Takako Inoue is currently supported by research grants from Gilead Sciences and MSD.KK Atsushi Nakajima is currently conducting research sponsored by Mylan EPD GK An unrestricted grant is provided by EA Pharma Co., Ltd. Lecture fees were provided by EA Pharma Co., Ltd., Mylan EPD GK and Astellas Pharma Inc Yasuhito Tanaka is currently conducting research sponsored by Janssen Pharmaceutical K. K., Gilead Sciences and Board of Trustees of the Leland Stanford. Lecture fees were provided by Gilead Sciences. The other authors declare no conflict of interest. Funding Information: We thank Center for Advanced Instrumental and Educational Supports, Faculty of Agriculture, Kyushu University, for support with DNA sequencing on the MiSeq sequencer. Additionally, we thank Junichi Yamao, Akira Mitoro, Ryuichi Noguchi, Tadashi Namisaki, Masakazu Uejima, Tsuyoshi Mashitani, Kosuke Takeda, Mitsuteru Kitade, Naotaka Shimozato, Yasushi Okura, Kosuke Kaji, Hiroaki Takaya, Norihisa Nishimura, Yasuhiko Sawada, Shinya Sato, Kenichiro Seki, Soichiro Saikawa, Shintaro Ogawa, Hatsumi Koshiyama and Asami Yamaguchi for their support in collecting faecal samples; we thank all participant patients and healthy individuals for providing samples and personal information. We also thank Dr Michinori Kohara for providing the HCR6 strain, and Dr Kikuko Hotta for providing information on RNA-Seq in NAFLD patients. This research was supported by AMED under Grant Number JP18fk0210201h0002 and JP20fk0310101h0003, the Ministry of Education, Culture, Sports, Science, and Technology (20K08012), grant support from MSD, grant-in-aid from Gilead Sciences and grant-in-aid for research from Nagoya City University. Publisher Copyright: {\textcopyright} 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd",
year = "2022",
month = jan,
doi = "10.1111/liv.15041",
language = "English",
volume = "42",
pages = "124--134",
journal = "Liver International",
issn = "1478-3223",
publisher = "Wiley-Blackwell",
number = "1",
}
