Depletion of gut microbiota induces skeletal muscle atrophy by FXR-FGF15/19 signalling
AbstractBackground: Recent evidence indicates that host-gut microbiota crosstalk has nonnegligible effects on host skeletal muscle, yet gut microbiota-regulating mechanisms remain obscure.Methods: C57BL/6 mice were treated with a cocktail of antibiotics (Abx) to depress gut microbiota for 4 weeks. T...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2021-01-01
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| Series: | Annals of Medicine |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/07853890.2021.1900593 |
| _version_ | 1797385706402742272 |
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| author | Yixuan Qiu Jiaming Yu Yi Li Fan Yang Huiyuan Yu Mengjuan Xue Fan Zhang Xin Jiang Xueying Ji Zhijun Bao |
| author_facet | Yixuan Qiu Jiaming Yu Yi Li Fan Yang Huiyuan Yu Mengjuan Xue Fan Zhang Xin Jiang Xueying Ji Zhijun Bao |
| author_sort | Yixuan Qiu |
| collection | DOAJ |
| description | AbstractBackground: Recent evidence indicates that host-gut microbiota crosstalk has nonnegligible effects on host skeletal muscle, yet gut microbiota-regulating mechanisms remain obscure.Methods: C57BL/6 mice were treated with a cocktail of antibiotics (Abx) to depress gut microbiota for 4 weeks. The profiles of gut microbiota and microbial bile acids were measured by 16S rRNA sequencing and ultra-performance liquid chromatography (UPLC), respectively. We performed qPCR, western blot and ELISA assays in different tissue samples to evaluate FXR-FGF15/19 signaling.Results: Abx treatment induced skeletal muscle atrophy in mice. These effects were associated with microbial dysbiosis and aberrant bile acid (BA) metabolism in intestine. Ileal farnesoid X receptor (FXR)-fibroblast growth factor 15 (FGF15) signaling was inhibited in response to microbial BA disturbance. Mechanistically, circulating FGF15 was decreased, which downregulated skeletal muscle protein synthesis through the extracellular-signal-regulated protein kinase 1/2 (ERK1/2) signaling pathway. Treating Abx mice with FGF19 (human FGF15 ortholog) partly reversed skeletal muscle loss.Conclusions: These findings indicate that the BA-FXR-FGF15/19 axis acts as a regulator of gut microbiota to mediate host skeletal muscle. |
| first_indexed | 2024-03-08T21:58:10Z |
| format | Article |
| id | doaj.art-9250cbf90ac04eaf98a3b72d1d4e5806 |
| institution | Directory Open Access Journal |
| issn | 0785-3890 1365-2060 |
| language | English |
| last_indexed | 2024-03-08T21:58:10Z |
| publishDate | 2021-01-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Annals of Medicine |
| spelling | doaj.art-9250cbf90ac04eaf98a3b72d1d4e58062023-12-19T16:46:27ZengTaylor & Francis GroupAnnals of Medicine0785-38901365-20602021-01-0153150852210.1080/07853890.2021.1900593Depletion of gut microbiota induces skeletal muscle atrophy by FXR-FGF15/19 signallingYixuan Qiu0Jiaming Yu1Yi Li2Fan Yang3Huiyuan Yu4Mengjuan Xue5Fan Zhang6Xin Jiang7Xueying Ji8Zhijun Bao9Department of Gerontology, Huadong Hospital Affiliated to Fudan University, Shanghai, ChinaDepartment of Gerontology, Huadong Hospital Affiliated to Fudan University, Shanghai, ChinaDepartment of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, ChinaDepartment of Gerontology, Huadong Hospital Affiliated to Fudan University, Shanghai, ChinaDepartment of Gerontology, Huadong Hospital Affiliated to Fudan University, Shanghai, ChinaDepartment of Gerontology, Huadong Hospital Affiliated to Fudan University, Shanghai, ChinaDepartment of Gerontology, Huadong Hospital Affiliated to Fudan University, Shanghai, ChinaDepartment of Gerontology, Huadong Hospital Affiliated to Fudan University, Shanghai, ChinaDepartment of Gerontology, Huadong Hospital Affiliated to Fudan University, Shanghai, ChinaDepartment of Gerontology, Huadong Hospital Affiliated to Fudan University, Shanghai, ChinaAbstractBackground: Recent evidence indicates that host-gut microbiota crosstalk has nonnegligible effects on host skeletal muscle, yet gut microbiota-regulating mechanisms remain obscure.Methods: C57BL/6 mice were treated with a cocktail of antibiotics (Abx) to depress gut microbiota for 4 weeks. The profiles of gut microbiota and microbial bile acids were measured by 16S rRNA sequencing and ultra-performance liquid chromatography (UPLC), respectively. We performed qPCR, western blot and ELISA assays in different tissue samples to evaluate FXR-FGF15/19 signaling.Results: Abx treatment induced skeletal muscle atrophy in mice. These effects were associated with microbial dysbiosis and aberrant bile acid (BA) metabolism in intestine. Ileal farnesoid X receptor (FXR)-fibroblast growth factor 15 (FGF15) signaling was inhibited in response to microbial BA disturbance. Mechanistically, circulating FGF15 was decreased, which downregulated skeletal muscle protein synthesis through the extracellular-signal-regulated protein kinase 1/2 (ERK1/2) signaling pathway. Treating Abx mice with FGF19 (human FGF15 ortholog) partly reversed skeletal muscle loss.Conclusions: These findings indicate that the BA-FXR-FGF15/19 axis acts as a regulator of gut microbiota to mediate host skeletal muscle.https://www.tandfonline.com/doi/10.1080/07853890.2021.1900593Gut microbiotaskeletal musclebile acidFXRFGF15/19 |
| spellingShingle | Yixuan Qiu Jiaming Yu Yi Li Fan Yang Huiyuan Yu Mengjuan Xue Fan Zhang Xin Jiang Xueying Ji Zhijun Bao Depletion of gut microbiota induces skeletal muscle atrophy by FXR-FGF15/19 signalling Annals of Medicine Gut microbiota skeletal muscle bile acid FXR FGF15/19 |
| title | Depletion of gut microbiota induces skeletal muscle atrophy by FXR-FGF15/19 signalling |
| title_full | Depletion of gut microbiota induces skeletal muscle atrophy by FXR-FGF15/19 signalling |
| title_fullStr | Depletion of gut microbiota induces skeletal muscle atrophy by FXR-FGF15/19 signalling |
| title_full_unstemmed | Depletion of gut microbiota induces skeletal muscle atrophy by FXR-FGF15/19 signalling |
| title_short | Depletion of gut microbiota induces skeletal muscle atrophy by FXR-FGF15/19 signalling |
| title_sort | depletion of gut microbiota induces skeletal muscle atrophy by fxr fgf15 19 signalling |
| topic | Gut microbiota skeletal muscle bile acid FXR FGF15/19 |
| url | https://www.tandfonline.com/doi/10.1080/07853890.2021.1900593 |
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