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...
Main Authors: | , , , , , , , , |
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Format: | Article |
Language: | English |
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Wolters Kluwer Health/LWW
2021-12-01
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Series: | Hepatology Communications |
Online Access: | https://doi.org/10.1002/hep4.1778 |
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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 |
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