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...

Full description

Bibliographic Details
Main Authors: Junichi Iwamoto, Akira Honda, Teruo Miyazaki, Tadakuni Monma, Hajime Ueda, Yukio Morishita, Sho‐ichiro Yara, Takeshi Hirayama, Tadashi Ikegami
Format: Article
Language:English
Published: Wolters Kluwer Health/LWW 2021-12-01
Series:Hepatology Communications
Online Access:https://doi.org/10.1002/hep4.1778
_version_ 1797935499157962752
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
collection DOAJ
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.
first_indexed 2024-04-10T18:15:13Z
format Article
id doaj.art-d3534b94f73f41c186aaf3c254ebfbff
institution Directory Open Access Journal
issn 2471-254X
language English
last_indexed 2024-04-10T18:15:13Z
publishDate 2021-12-01
publisher Wolters Kluwer Health/LWW
record_format Article
series Hepatology Communications
spelling doaj.art-d3534b94f73f41c186aaf3c254ebfbff2023-02-02T09:07:47ZengWolters Kluwer Health/LWWHepatology Communications2471-254X2021-12-015122052206710.1002/hep4.1778Western Diet Changes Gut Microbiota and Ameliorates Liver Injury in a Mouse Model with Human‐Like Bile Acid CompositionJunichi Iwamoto0Akira Honda1Teruo Miyazaki2Tadakuni Monma3Hajime Ueda4Yukio Morishita5Sho‐ichiro Yara6Takeshi Hirayama7Tadashi Ikegami8Division of Gastroenterology and Hepatology Tokyo Medical University Ibaraki Medical Center Ibaraki JapanDivision of Gastroenterology and Hepatology Tokyo Medical University Ibaraki Medical Center Ibaraki JapanJoint Research Center Tokyo Medical University Ibaraki Medical Center Ibaraki JapanDivision of Gastroenterology and Hepatology Tokyo Medical University Ibaraki Medical Center Ibaraki JapanDivision of Gastroenterology and Hepatology Tokyo Medical University Ibaraki Medical Center Ibaraki JapanDiagnostic Pathology Division Tokyo Medical University Ibaraki Medical Center Ibaraki JapanDivision of Gastroenterology and Hepatology Tokyo Medical University Ibaraki Medical Center Ibaraki JapanDivision of Gastroenterology and Hepatology Tokyo Medical University Ibaraki Medical Center Ibaraki JapanDivision of Gastroenterology and Hepatology Tokyo Medical University Ibaraki Medical Center Ibaraki JapanWestern‐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.https://doi.org/10.1002/hep4.1778
spellingShingle 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
Hepatology Communications
title 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_short 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
url https://doi.org/10.1002/hep4.1778
work_keys_str_mv AT junichiiwamoto westerndietchangesgutmicrobiotaandamelioratesliverinjuryinamousemodelwithhumanlikebileacidcomposition
AT akirahonda westerndietchangesgutmicrobiotaandamelioratesliverinjuryinamousemodelwithhumanlikebileacidcomposition
AT teruomiyazaki westerndietchangesgutmicrobiotaandamelioratesliverinjuryinamousemodelwithhumanlikebileacidcomposition
AT tadakunimonma westerndietchangesgutmicrobiotaandamelioratesliverinjuryinamousemodelwithhumanlikebileacidcomposition
AT hajimeueda westerndietchangesgutmicrobiotaandamelioratesliverinjuryinamousemodelwithhumanlikebileacidcomposition
AT yukiomorishita westerndietchangesgutmicrobiotaandamelioratesliverinjuryinamousemodelwithhumanlikebileacidcomposition
AT shoichiroyara westerndietchangesgutmicrobiotaandamelioratesliverinjuryinamousemodelwithhumanlikebileacidcomposition
AT takeshihirayama westerndietchangesgutmicrobiotaandamelioratesliverinjuryinamousemodelwithhumanlikebileacidcomposition
AT tadashiikegami westerndietchangesgutmicrobiotaandamelioratesliverinjuryinamousemodelwithhumanlikebileacidcomposition