A dysregulated bile acid-gut microbiota axis contributes to obesity susceptibility
Background: The composition of the bile acid (BA) pool is closely associated with obesity and is modified by gut microbiota. Perturbations of gut microbiota shape the BA composition, which, in turn, may alter important BA signaling and affect host metabolism. Methods: We investigated BA composition...
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| Language: | English |
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Elsevier
2020-05-01
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| Series: | EBioMedicine |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396420301419 |
| _version_ | 1819079146746150912 |
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| author | Meilin Wei Fengjie Huang Ling Zhao Yunjing Zhang Wei Yang Shouli Wang Mengci Li Xiaolong Han Kun Ge Chun Qu Cynthia Rajani Guoxiang Xie Xiaojiao Zheng Aihua Zhao Zhaoxiang Bian Wei Jia |
| author_facet | Meilin Wei Fengjie Huang Ling Zhao Yunjing Zhang Wei Yang Shouli Wang Mengci Li Xiaolong Han Kun Ge Chun Qu Cynthia Rajani Guoxiang Xie Xiaojiao Zheng Aihua Zhao Zhaoxiang Bian Wei Jia |
| author_sort | Meilin Wei |
| collection | DOAJ |
| description | Background: The composition of the bile acid (BA) pool is closely associated with obesity and is modified by gut microbiota. Perturbations of gut microbiota shape the BA composition, which, in turn, may alter important BA signaling and affect host metabolism. Methods: We investigated BA composition of high BMI subjects from a human cohort study and a high fat diet (HFD) obesity prone (HF-OP) / HFD obesity resistant (HF-OR) mice model. Gut microbiota was analysed by metagenomics sequencing. GLP-1 secretion and gene regulation studies involved ELISA, qPCR, Western blot, Immunohistochemistry, and Immunofluorescence staining. Findings: We found that the proportion of non-12-OH BAs was significantly decreased in the unhealthy high BMI subjects. The HF-OR mice had an enhanced level of non-12-OH BAs. Non-12-OH BAs including ursodeoxycholate (UDCA), chenodeoxycholate (CDCA), and lithocholate (LCA) were decreased in the HF-OP mice and associated with altered gut microbiota. Clostridium scindens was decreased in HF-OP mice and had a positive correlation with UDCA and LCA. Gavage of Clostridium scindens in mice increased the levels of hepatic non-12-OH BAs, accompanied by elevated serum 7α-hydroxy-4-cholesten-3-one (C4) levels. In HF-OP mice, altered BA composition was associated with significantly downregulated expression of GLP-1 in ileum and PGC1α, UCP1 in brown adipose tissue. In addition, we identified that UDCA attenuated the high fat diet-induced obesity via enhancing levels of non-12-OH BAs. Interpretation: Our study highlights that dysregulated BA signaling mediated by gut microbiota contributes to obesity susceptibility, suggesting modulation of BAs could be a promising strategy for obesity therapy. |
| first_indexed | 2024-12-21T19:24:21Z |
| format | Article |
| id | doaj.art-7a8af9d82cb44c149312a57a328f3983 |
| institution | Directory Open Access Journal |
| issn | 2352-3964 |
| language | English |
| last_indexed | 2024-12-21T19:24:21Z |
| publishDate | 2020-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EBioMedicine |
| spelling | doaj.art-7a8af9d82cb44c149312a57a328f39832022-12-21T18:52:52ZengElsevierEBioMedicine2352-39642020-05-0155A dysregulated bile acid-gut microbiota axis contributes to obesity susceptibilityMeilin Wei0Fengjie Huang1Ling Zhao2Yunjing Zhang3Wei Yang4Shouli Wang5Mengci Li6Xiaolong Han7Kun Ge8Chun Qu9Cynthia Rajani10Guoxiang Xie11Xiaojiao Zheng12Aihua Zhao13Zhaoxiang Bian14Wei Jia15Shanghai Key Laboratory of Diabetes Mellitus and Centre for Translational Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, ChinaShanghai Key Laboratory of Diabetes Mellitus and Centre for Translational Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, ChinaSchool of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, ChinaShanghai Key Laboratory of Diabetes Mellitus and Centre for Translational Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, ChinaSchool of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, ChinaShanghai Key Laboratory of Diabetes Mellitus and Centre for Translational Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, ChinaShanghai Key Laboratory of Diabetes Mellitus and Centre for Translational Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, ChinaShanghai Key Laboratory of Diabetes Mellitus and Centre for Translational Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, ChinaShanghai Key Laboratory of Diabetes Mellitus and Centre for Translational Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, ChinaShanghai Key Laboratory of Diabetes Mellitus and Centre for Translational Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, ChinaUniversity of Hawaii Cancer Centre, 701 Ilalo st, Honolulu, HI 96813, USAShanghai Key Laboratory of Diabetes Mellitus and Centre for Translational Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China; University of Hawaii Cancer Centre, 701 Ilalo st, Honolulu, HI 96813, USAShanghai Key Laboratory of Diabetes Mellitus and Centre for Translational Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, ChinaShanghai Key Laboratory of Diabetes Mellitus and Centre for Translational Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, ChinaSchool of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China; Corresponding author.Shanghai Key Laboratory of Diabetes Mellitus and Centre for Translational Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China; University of Hawaii Cancer Centre, 701 Ilalo st, Honolulu, HI 96813, USA; School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China; Corresponding author at: Shanghai Key Laboratory of Diabetes Mellitus and Centre for Translational Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China.Background: The composition of the bile acid (BA) pool is closely associated with obesity and is modified by gut microbiota. Perturbations of gut microbiota shape the BA composition, which, in turn, may alter important BA signaling and affect host metabolism. Methods: We investigated BA composition of high BMI subjects from a human cohort study and a high fat diet (HFD) obesity prone (HF-OP) / HFD obesity resistant (HF-OR) mice model. Gut microbiota was analysed by metagenomics sequencing. GLP-1 secretion and gene regulation studies involved ELISA, qPCR, Western blot, Immunohistochemistry, and Immunofluorescence staining. Findings: We found that the proportion of non-12-OH BAs was significantly decreased in the unhealthy high BMI subjects. The HF-OR mice had an enhanced level of non-12-OH BAs. Non-12-OH BAs including ursodeoxycholate (UDCA), chenodeoxycholate (CDCA), and lithocholate (LCA) were decreased in the HF-OP mice and associated with altered gut microbiota. Clostridium scindens was decreased in HF-OP mice and had a positive correlation with UDCA and LCA. Gavage of Clostridium scindens in mice increased the levels of hepatic non-12-OH BAs, accompanied by elevated serum 7α-hydroxy-4-cholesten-3-one (C4) levels. In HF-OP mice, altered BA composition was associated with significantly downregulated expression of GLP-1 in ileum and PGC1α, UCP1 in brown adipose tissue. In addition, we identified that UDCA attenuated the high fat diet-induced obesity via enhancing levels of non-12-OH BAs. Interpretation: Our study highlights that dysregulated BA signaling mediated by gut microbiota contributes to obesity susceptibility, suggesting modulation of BAs could be a promising strategy for obesity therapy.http://www.sciencedirect.com/science/article/pii/S2352396420301419ObesityBile acidsGut microbiotaEnergy expenditureGLP-1UCP1 |
| spellingShingle | Meilin Wei Fengjie Huang Ling Zhao Yunjing Zhang Wei Yang Shouli Wang Mengci Li Xiaolong Han Kun Ge Chun Qu Cynthia Rajani Guoxiang Xie Xiaojiao Zheng Aihua Zhao Zhaoxiang Bian Wei Jia A dysregulated bile acid-gut microbiota axis contributes to obesity susceptibility EBioMedicine Obesity Bile acids Gut microbiota Energy expenditure GLP-1 UCP1 |
| title | A dysregulated bile acid-gut microbiota axis contributes to obesity susceptibility |
| title_full | A dysregulated bile acid-gut microbiota axis contributes to obesity susceptibility |
| title_fullStr | A dysregulated bile acid-gut microbiota axis contributes to obesity susceptibility |
| title_full_unstemmed | A dysregulated bile acid-gut microbiota axis contributes to obesity susceptibility |
| title_short | A dysregulated bile acid-gut microbiota axis contributes to obesity susceptibility |
| title_sort | dysregulated bile acid gut microbiota axis contributes to obesity susceptibility |
| topic | Obesity Bile acids Gut microbiota Energy expenditure GLP-1 UCP1 |
| url | http://www.sciencedirect.com/science/article/pii/S2352396420301419 |
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