Canagliflozin attenuates kidney injury, gut-derived toxins, and gut microbiota imbalance in high-salt diet-fed Dahl salt-sensitive rats
Purpose To investigate the effects of canagliflozin (20 mg/kg) on Dahl salt-sensitive (DSS) rat gut microbiota and salt-sensitive hypertension-induced kidney injury and further explore its possible mechanism.Methods Rats were fed a high-salt diet to induce hypertension and kidney injury, and physica...
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| Format: | Article |
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Taylor & Francis Group
2024-12-01
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| Series: | Renal Failure |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/0886022X.2023.2300314 |
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| author | Lili He Qingjuan Zuo Sai Ma Guorui Zhang Zhongli Wang Tingting Zhang Jianlong Zhai Yifang Guo |
| author_facet | Lili He Qingjuan Zuo Sai Ma Guorui Zhang Zhongli Wang Tingting Zhang Jianlong Zhai Yifang Guo |
| author_sort | Lili He |
| collection | DOAJ |
| description | Purpose To investigate the effects of canagliflozin (20 mg/kg) on Dahl salt-sensitive (DSS) rat gut microbiota and salt-sensitive hypertension-induced kidney injury and further explore its possible mechanism.Methods Rats were fed a high-salt diet to induce hypertension and kidney injury, and physical and physiological indicators were measured afterwards. This study employed 16S rRNA sequencing technology and liquid chromatography–tandem mass spectrometry (LC–MS/MS)-based metabolic profiling combined with advanced differential and association analyses to investigate the correlation between the microbiome and the metabolome in male DSS rats.Results A high-salt diet disrupted the balance of the intestinal flora and increased toxic metabolites (methyhistidines, creatinine, homocitrulline, and indoxyl sulfate), resulting in severe kidney damage. Canagliflozin contributed to reconstructing the intestinal flora of DSS rats by significantly increasing the abundance of Corynebacterium spp., Bifidobacterium spp., Facklamia spp., Lactobacillus spp., Ruminococcus spp., Blautia spp., Coprococcus spp., and Allobaculum spp. Moreover, the reconstruction of the intestinal microbiota led to significant changes in host amino acid metabolite concentrations. The concentration of uremic toxins, such as methyhistidines, creatinine, and homocitrulline, in the serum of rats was decreased by canagliflozin, which resulted in oxidative stress and renal injury alleviation.Conclusion Canagliflozin may change the production of metabolites and reduce the level of uremic toxins in the blood circulation by reconstructing the intestinal flora of DSS rats fed a high-salt diet, ultimately alleviating oxidative stress and renal injury. |
| format | Article |
| id | doaj-art-58889af7424a453b90e6376a55939d37 |
| institution | Kabale University |
| issn | 0886-022X 1525-6049 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Renal Failure |
| spelling | doaj-art-58889af7424a453b90e6376a55939d372025-01-23T04:17:49ZengTaylor & Francis GroupRenal Failure0886-022X1525-60492024-12-0146110.1080/0886022X.2023.2300314Canagliflozin attenuates kidney injury, gut-derived toxins, and gut microbiota imbalance in high-salt diet-fed Dahl salt-sensitive ratsLili He0Qingjuan Zuo1Sai Ma2Guorui Zhang3Zhongli Wang4Tingting Zhang5Jianlong Zhai6Yifang Guo7Department of Geriatric Cardiology, Hebei General Hospital, Shijiazhuang, ChinaDepartment of Geriatric Cardiology, Hebei General Hospital, Shijiazhuang, ChinaDepartment of Internal Medicine, Hebei General Hospital, Shijiazhuang, ChinaDepartment of Cardiology, The Third Hospital of Shijiazhuang City Affiliated to Hebei Medical University, Shijiazhuang, ChinaDepartment of Physical Examination Center, Hebei General Hospital, Shijiazhuang, ChinaDepartment of Geriatric Cardiology, Hebei General Hospital, Shijiazhuang, ChinaDepartment of Cardiology, Hebei General Hospital, Shijiazhuang, ChinaDepartment of Geriatric Cardiology, Hebei General Hospital, Shijiazhuang, ChinaPurpose To investigate the effects of canagliflozin (20 mg/kg) on Dahl salt-sensitive (DSS) rat gut microbiota and salt-sensitive hypertension-induced kidney injury and further explore its possible mechanism.Methods Rats were fed a high-salt diet to induce hypertension and kidney injury, and physical and physiological indicators were measured afterwards. This study employed 16S rRNA sequencing technology and liquid chromatography–tandem mass spectrometry (LC–MS/MS)-based metabolic profiling combined with advanced differential and association analyses to investigate the correlation between the microbiome and the metabolome in male DSS rats.Results A high-salt diet disrupted the balance of the intestinal flora and increased toxic metabolites (methyhistidines, creatinine, homocitrulline, and indoxyl sulfate), resulting in severe kidney damage. Canagliflozin contributed to reconstructing the intestinal flora of DSS rats by significantly increasing the abundance of Corynebacterium spp., Bifidobacterium spp., Facklamia spp., Lactobacillus spp., Ruminococcus spp., Blautia spp., Coprococcus spp., and Allobaculum spp. Moreover, the reconstruction of the intestinal microbiota led to significant changes in host amino acid metabolite concentrations. The concentration of uremic toxins, such as methyhistidines, creatinine, and homocitrulline, in the serum of rats was decreased by canagliflozin, which resulted in oxidative stress and renal injury alleviation.Conclusion Canagliflozin may change the production of metabolites and reduce the level of uremic toxins in the blood circulation by reconstructing the intestinal flora of DSS rats fed a high-salt diet, ultimately alleviating oxidative stress and renal injury.https://www.tandfonline.com/doi/10.1080/0886022X.2023.2300314Gut microbiotaserum metaboliteshypertensionkidney injurycanagliflozin |
| spellingShingle | Lili He Qingjuan Zuo Sai Ma Guorui Zhang Zhongli Wang Tingting Zhang Jianlong Zhai Yifang Guo Canagliflozin attenuates kidney injury, gut-derived toxins, and gut microbiota imbalance in high-salt diet-fed Dahl salt-sensitive rats Renal Failure Gut microbiota serum metabolites hypertension kidney injury canagliflozin |
| title | Canagliflozin attenuates kidney injury, gut-derived toxins, and gut microbiota imbalance in high-salt diet-fed Dahl salt-sensitive rats |
| title_full | Canagliflozin attenuates kidney injury, gut-derived toxins, and gut microbiota imbalance in high-salt diet-fed Dahl salt-sensitive rats |
| title_fullStr | Canagliflozin attenuates kidney injury, gut-derived toxins, and gut microbiota imbalance in high-salt diet-fed Dahl salt-sensitive rats |
| title_full_unstemmed | Canagliflozin attenuates kidney injury, gut-derived toxins, and gut microbiota imbalance in high-salt diet-fed Dahl salt-sensitive rats |
| title_short | Canagliflozin attenuates kidney injury, gut-derived toxins, and gut microbiota imbalance in high-salt diet-fed Dahl salt-sensitive rats |
| title_sort | canagliflozin attenuates kidney injury gut derived toxins and gut microbiota imbalance in high salt diet fed dahl salt sensitive rats |
| topic | Gut microbiota serum metabolites hypertension kidney injury canagliflozin |
| url | https://www.tandfonline.com/doi/10.1080/0886022X.2023.2300314 |
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