Gut microbiota-bile acid crosstalk regulates murine lipid metabolism via the intestinal FXR-FGF19 axis in diet-induced humanized dyslipidemia
Abstract Background Diet-induced dyslipidemia is linked to the gut microbiota, but the causality of microbiota-host interaction affecting lipid metabolism remains controversial. Here, the humanized dyslipidemia mice model was successfully built by using fecal microbiota transplantation from dyslipid...
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| Format: | Article |
| Language: | English |
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BMC
2023-11-01
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| Series: | Microbiome |
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| Online Access: | https://doi.org/10.1186/s40168-023-01709-5 |
| _version_ | 1797452093239328768 |
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| author | Hongtao Xu Fang Fang Kaizhang Wu Jiangping Song Yaqian Li Xingyu Lu Juncheng Liu Liuyang Zhou Wenqing Yu Fei Yu Jie Gao |
| author_facet | Hongtao Xu Fang Fang Kaizhang Wu Jiangping Song Yaqian Li Xingyu Lu Juncheng Liu Liuyang Zhou Wenqing Yu Fei Yu Jie Gao |
| author_sort | Hongtao Xu |
| collection | DOAJ |
| description | Abstract Background Diet-induced dyslipidemia is linked to the gut microbiota, but the causality of microbiota-host interaction affecting lipid metabolism remains controversial. Here, the humanized dyslipidemia mice model was successfully built by using fecal microbiota transplantation from dyslipidemic donors (FMT-dd) to study the causal role of gut microbiota in diet-induced dyslipidemia. Results We demonstrated that FMT-dd reshaped the gut microbiota of mice by increasing Faecalibaculum and Ruminococcaceae UCG-010, which then elevated serum cholicacid (CA), chenodeoxycholic acid (CDCA), and deoxycholic acid (DCA), reduced bile acid synthesis and increased cholesterol accumulation via the hepatic farnesoid X receptor-small heterodimer partner (FXR-SHP) axis. Nevertheless, high-fat diet led to decreased Muribaculum in the humanized dyslipidemia mice induced by FMT-dd, which resulted in reduced intestinal hyodeoxycholic acid (HDCA), raised bile acid synthesis and increased lipid absorption via the intestinal farnesoid X receptor-fibroblast growth factor 19 (FXR-FGF19) axis. Conclusions Our studies implicated that intestinal FXR is responsible for the regulation of lipid metabolism in diet-induced dyslipidemia mediated by gut microbiota-bile acid crosstalk. Video Abstract |
| first_indexed | 2024-03-09T15:02:49Z |
| format | Article |
| id | doaj.art-3c721047a46d49b596bb4779922463a7 |
| institution | Directory Open Access Journal |
| issn | 2049-2618 |
| language | English |
| last_indexed | 2024-03-09T15:02:49Z |
| publishDate | 2023-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Microbiome |
| spelling | doaj.art-3c721047a46d49b596bb4779922463a72023-11-26T13:47:30ZengBMCMicrobiome2049-26182023-11-0111111610.1186/s40168-023-01709-5Gut microbiota-bile acid crosstalk regulates murine lipid metabolism via the intestinal FXR-FGF19 axis in diet-induced humanized dyslipidemiaHongtao Xu0Fang Fang1Kaizhang Wu2Jiangping Song3Yaqian Li4Xingyu Lu5Juncheng Liu6Liuyang Zhou7Wenqing Yu8Fei Yu9Jie Gao10School of Light Industry and Food Engineering, Guangxi UniversitySchool of Light Industry and Food Engineering, Guangxi UniversitySchool of Light Industry and Food Engineering, Guangxi UniversitySchool of Light Industry and Food Engineering, Guangxi UniversitySchool of Light Industry and Food Engineering, Guangxi UniversitySchool of Light Industry and Food Engineering, Guangxi UniversitySchool of Light Industry and Food Engineering, Guangxi UniversitySchool of Light Industry and Food Engineering, Guangxi UniversitySchool of Light Industry and Food Engineering, Guangxi UniversityMedical College, Guangxi UniversitySchool of Light Industry and Food Engineering, Guangxi UniversityAbstract Background Diet-induced dyslipidemia is linked to the gut microbiota, but the causality of microbiota-host interaction affecting lipid metabolism remains controversial. Here, the humanized dyslipidemia mice model was successfully built by using fecal microbiota transplantation from dyslipidemic donors (FMT-dd) to study the causal role of gut microbiota in diet-induced dyslipidemia. Results We demonstrated that FMT-dd reshaped the gut microbiota of mice by increasing Faecalibaculum and Ruminococcaceae UCG-010, which then elevated serum cholicacid (CA), chenodeoxycholic acid (CDCA), and deoxycholic acid (DCA), reduced bile acid synthesis and increased cholesterol accumulation via the hepatic farnesoid X receptor-small heterodimer partner (FXR-SHP) axis. Nevertheless, high-fat diet led to decreased Muribaculum in the humanized dyslipidemia mice induced by FMT-dd, which resulted in reduced intestinal hyodeoxycholic acid (HDCA), raised bile acid synthesis and increased lipid absorption via the intestinal farnesoid X receptor-fibroblast growth factor 19 (FXR-FGF19) axis. Conclusions Our studies implicated that intestinal FXR is responsible for the regulation of lipid metabolism in diet-induced dyslipidemia mediated by gut microbiota-bile acid crosstalk. Video Abstracthttps://doi.org/10.1186/s40168-023-01709-5Gut microbiotaBile acidLipid metabolismFXRDiet-induced humanized dyslipidemia |
| spellingShingle | Hongtao Xu Fang Fang Kaizhang Wu Jiangping Song Yaqian Li Xingyu Lu Juncheng Liu Liuyang Zhou Wenqing Yu Fei Yu Jie Gao Gut microbiota-bile acid crosstalk regulates murine lipid metabolism via the intestinal FXR-FGF19 axis in diet-induced humanized dyslipidemia Microbiome Gut microbiota Bile acid Lipid metabolism FXR Diet-induced humanized dyslipidemia |
| title | Gut microbiota-bile acid crosstalk regulates murine lipid metabolism via the intestinal FXR-FGF19 axis in diet-induced humanized dyslipidemia |
| title_full | Gut microbiota-bile acid crosstalk regulates murine lipid metabolism via the intestinal FXR-FGF19 axis in diet-induced humanized dyslipidemia |
| title_fullStr | Gut microbiota-bile acid crosstalk regulates murine lipid metabolism via the intestinal FXR-FGF19 axis in diet-induced humanized dyslipidemia |
| title_full_unstemmed | Gut microbiota-bile acid crosstalk regulates murine lipid metabolism via the intestinal FXR-FGF19 axis in diet-induced humanized dyslipidemia |
| title_short | Gut microbiota-bile acid crosstalk regulates murine lipid metabolism via the intestinal FXR-FGF19 axis in diet-induced humanized dyslipidemia |
| title_sort | gut microbiota bile acid crosstalk regulates murine lipid metabolism via the intestinal fxr fgf19 axis in diet induced humanized dyslipidemia |
| topic | Gut microbiota Bile acid Lipid metabolism FXR Diet-induced humanized dyslipidemia |
| url | https://doi.org/10.1186/s40168-023-01709-5 |
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