Western Diet Changes Gut Microbiota and Ameliorates Liver Injury in a Mouse Model with Human‐Like Bile Acid Composition

Western‐style high‐fat/high‐sucrose diet (HFHSD) changes gut microbiota and bile acid (BA) profiles. Because gut microbiota and BAs could influence each other, the mechanism of changes in both by HFHSD is complicated and remains unclear. We first aimed to clarify the roles of BAs in the HFHSD‐induce...

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Autores principales: Junichi Iwamoto, Akira Honda, Teruo Miyazaki, Tadakuni Monma, Hajime Ueda, Yukio Morishita, Sho‐ichiro Yara, Takeshi Hirayama, Tadashi Ikegami
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Publicado: Wiley 2021
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spelling oai:doaj.org-article:d3534b94f73f41c186aaf3c254ebfbff2021-11-30T13:39:17ZWestern Diet Changes Gut Microbiota and Ameliorates Liver Injury in a Mouse Model with Human‐Like Bile Acid Composition2471-254X10.1002/hep4.1778https://doaj.org/article/d3534b94f73f41c186aaf3c254ebfbff2021-12-01T00:00:00Zhttps://doi.org/10.1002/hep4.1778https://doaj.org/toc/2471-254XWestern‐style high‐fat/high‐sucrose diet (HFHSD) changes gut microbiota and bile acid (BA) profiles. Because gut microbiota and BAs could influence each other, the mechanism of changes in both by HFHSD is complicated and remains unclear. We first aimed to clarify the roles of BAs in the HFHSD‐induced change of gut microbiota. Then, we studied the effects of the changed gut microbiota on BA composition and liver function. Male wild‐type (WT) and human‐like Cyp2a12/Cyp2c70 double knockout (DKO) mice derived from C57BL/6J were fed with normal chow or HFHSD for 4 weeks. Gut microbiomes were analyzed by fecal 16S ribosomal RNA gene sequencing, and BA composition was determined by liquid chromatography–tandem mass spectrometry. The DKO mice exhibited significantly reduced fecal BA concentration, lacked muricholic acids, and increased proportions of chenodeoxycholic and lithocholic acids. Despite the marked difference in the fecal BA composition, the profiles of gut microbiota in the two mouse models were quite similar. An HFHSD resulted in a significant increase in the BA pool and fecal BA excretion in WT mice but not in DKO mice. However, microbial composition in the two mouse models was drastically but similarly changed by the HFHSD. In addition, the HFHSD‐induced change of gut microbiota inhibited BA deconjugation and 7α‐dehydroxylation in both types of mice, which improved chronic liver injury observed in DKO mice. Conclusion: The HFHSD itself causes the change of gut microbiota due to HFHSD, and the altered composition or concentration of BAs by HFHSD is not the primary factor. On the contrary, the gut microbiota formed by HFHSD affects BA composition and ameliorates liver injury in the mouse model with human‐like hydrophobic BA composition.Junichi IwamotoAkira HondaTeruo MiyazakiTadakuni MonmaHajime UedaYukio MorishitaSho‐ichiro YaraTakeshi HirayamaTadashi IkegamiWileyarticleDiseases of the digestive system. GastroenterologyRC799-869ENHepatology Communications, Vol 5, Iss 12, Pp 2052-2067 (2021)
institution DOAJ
collection DOAJ
language EN
topic Diseases of the digestive system. Gastroenterology
RC799-869
spellingShingle Diseases of the digestive system. Gastroenterology
RC799-869
Junichi Iwamoto
Akira Honda
Teruo Miyazaki
Tadakuni Monma
Hajime Ueda
Yukio Morishita
Sho‐ichiro Yara
Takeshi Hirayama
Tadashi Ikegami
Western Diet Changes Gut Microbiota and Ameliorates Liver Injury in a Mouse Model with Human‐Like Bile Acid Composition
description Western‐style high‐fat/high‐sucrose diet (HFHSD) changes gut microbiota and bile acid (BA) profiles. Because gut microbiota and BAs could influence each other, the mechanism of changes in both by HFHSD is complicated and remains unclear. We first aimed to clarify the roles of BAs in the HFHSD‐induced change of gut microbiota. Then, we studied the effects of the changed gut microbiota on BA composition and liver function. Male wild‐type (WT) and human‐like Cyp2a12/Cyp2c70 double knockout (DKO) mice derived from C57BL/6J were fed with normal chow or HFHSD for 4 weeks. Gut microbiomes were analyzed by fecal 16S ribosomal RNA gene sequencing, and BA composition was determined by liquid chromatography–tandem mass spectrometry. The DKO mice exhibited significantly reduced fecal BA concentration, lacked muricholic acids, and increased proportions of chenodeoxycholic and lithocholic acids. Despite the marked difference in the fecal BA composition, the profiles of gut microbiota in the two mouse models were quite similar. An HFHSD resulted in a significant increase in the BA pool and fecal BA excretion in WT mice but not in DKO mice. However, microbial composition in the two mouse models was drastically but similarly changed by the HFHSD. In addition, the HFHSD‐induced change of gut microbiota inhibited BA deconjugation and 7α‐dehydroxylation in both types of mice, which improved chronic liver injury observed in DKO mice. Conclusion: The HFHSD itself causes the change of gut microbiota due to HFHSD, and the altered composition or concentration of BAs by HFHSD is not the primary factor. On the contrary, the gut microbiota formed by HFHSD affects BA composition and ameliorates liver injury in the mouse model with human‐like hydrophobic BA composition.
format article
author Junichi Iwamoto
Akira Honda
Teruo Miyazaki
Tadakuni Monma
Hajime Ueda
Yukio Morishita
Sho‐ichiro Yara
Takeshi Hirayama
Tadashi Ikegami
author_facet Junichi Iwamoto
Akira Honda
Teruo Miyazaki
Tadakuni Monma
Hajime Ueda
Yukio Morishita
Sho‐ichiro Yara
Takeshi Hirayama
Tadashi Ikegami
author_sort Junichi Iwamoto
title Western Diet Changes Gut Microbiota and Ameliorates Liver Injury in a Mouse Model with Human‐Like Bile Acid Composition
title_short Western Diet Changes Gut Microbiota and Ameliorates Liver Injury in a Mouse Model with Human‐Like Bile Acid Composition
title_full Western Diet Changes Gut Microbiota and Ameliorates Liver Injury in a Mouse Model with Human‐Like Bile Acid Composition
title_fullStr Western Diet Changes Gut Microbiota and Ameliorates Liver Injury in a Mouse Model with Human‐Like Bile Acid Composition
title_full_unstemmed Western Diet Changes Gut Microbiota and Ameliorates Liver Injury in a Mouse Model with Human‐Like Bile Acid Composition
title_sort western diet changes gut microbiota and ameliorates liver injury in a mouse model with human‐like bile acid composition
publisher Wiley
publishDate 2021
url https://doaj.org/article/d3534b94f73f41c186aaf3c254ebfbff
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