Sacubitril/Valsartan contributes to improving the diabetic kidney disease and regulating the gut microbiota in mice
BackgroundDiabetic kidney disease (DKD), as a serious microvascular complication of diabetes, has limted treatment options. It is reported that the Sacubitril/Valsartan (Sac/Val) can improve kidney function, and the disordered gut microbiota and part of its metabolites are related to the development...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-12-01
|
| Series: | Frontiers in Endocrinology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2022.1034818/full |
| _version_ | 1797980546397110272 |
|---|---|
| author | Peipei Wang Peipei Wang Ruixue Guo Ruixue Guo Xiwen Bai Wen Cui Wen Cui Yiding Zhang Yiding Zhang Huangmin Li Huangmin Li Jin Shang Jin Shang Jin Shang Zhanzheng Zhao Zhanzheng Zhao Zhanzheng Zhao |
| author_facet | Peipei Wang Peipei Wang Ruixue Guo Ruixue Guo Xiwen Bai Wen Cui Wen Cui Yiding Zhang Yiding Zhang Huangmin Li Huangmin Li Jin Shang Jin Shang Jin Shang Zhanzheng Zhao Zhanzheng Zhao Zhanzheng Zhao |
| author_sort | Peipei Wang |
| collection | DOAJ |
| description | BackgroundDiabetic kidney disease (DKD), as a serious microvascular complication of diabetes, has limted treatment options. It is reported that the Sacubitril/Valsartan (Sac/Val) can improve kidney function, and the disordered gut microbiota and part of its metabolites are related to the development of DKD. Therefore, we aim to explore whether the effect of Sac/Val on DKD is associated with the gut microbiota and related plasma metabolic profiles.MethodsMale C57BL/6J mice were randomly divided into 3 groups: Con group (n = 5), DKD group (n = 6), and Sac/Val group (n = 6) . Sac/Val group was treated with Sac/Val solution. The intervention was given once every 2 days for 6 weeks. We measured the blood glucose and urine protein level of mice at different times. We then collected samples at the end of experiment for the 16s rRNA gene sequencing analysis and the untargeted plasma metabonomic analysis.ResultsWe found that the plasma creatinine concentration of DKD-group mice was significantly higher than that of Con-group mice, whereas it was reduced after the Sac/Val treatment. Compared with DKD mice, Sac/Val treatment could decrease the expression of indicators related to EndMT and renal fibrosis like vimentin, collagen IV and fibronectin in kidney. According to the criteria of LDA ≥ 2.5 and p<0.05, LefSe analysis of gut microbiota identified 13 biomarkers in Con group, and 33 biomarkers in DKD group, mainly including Prevotella, Escherichia_Shigella and Christensenellaceae_R_7_group, etc. For the Sac/Val group, there were 21 biomarkers, such as Bacteroides, Rikenellaceae_RC9_gut_group, Parabacteroides, Lactobacillus, etc. Plasma metabolomics analysis identified a total of 648 metabolites, and 167 important differential metabolites were screened among groups. KEGG pathway of tryptophan metabolism: M and bile secretion: OS had the highest significance of enrichment.ConclusionsSac/Val improves the renal function of DKD mice by inhibiting renal fibrosis. This drug can also regulate gut microbiota in DKD mice. |
| first_indexed | 2024-04-11T05:57:03Z |
| format | Article |
| id | doaj.art-f6c02dc0c29a43a6bd1ff756a8eb7d13 |
| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-04-11T05:57:03Z |
| publishDate | 2022-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj.art-f6c02dc0c29a43a6bd1ff756a8eb7d132022-12-22T04:41:53ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922022-12-011310.3389/fendo.2022.10348181034818Sacubitril/Valsartan contributes to improving the diabetic kidney disease and regulating the gut microbiota in micePeipei Wang0Peipei Wang1Ruixue Guo2Ruixue Guo3Xiwen Bai4Wen Cui5Wen Cui6Yiding Zhang7Yiding Zhang8Huangmin Li9Huangmin Li10Jin Shang11Jin Shang12Jin Shang13Zhanzheng Zhao14Zhanzheng Zhao15Zhanzheng Zhao16Department of Nephrology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaZhengzhou University, Zhengzhou, ChinaDepartment of Nephrology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaZhengzhou University, Zhengzhou, ChinaNanchang University Queen Mary School, Nanchang, ChinaDepartment of Nephrology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaZhengzhou University, Zhengzhou, ChinaDepartment of Nephrology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaZhengzhou University, Zhengzhou, ChinaDepartment of Nephrology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaZhengzhou University, Zhengzhou, ChinaDepartment of Nephrology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaLaboratory Animal Platform of Academy of Medical Sciences, Zhengzhou University, Zhengzhou, ChinaNephropathy Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Nephrology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaLaboratory Animal Platform of Academy of Medical Sciences, Zhengzhou University, Zhengzhou, ChinaNephropathy Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaBackgroundDiabetic kidney disease (DKD), as a serious microvascular complication of diabetes, has limted treatment options. It is reported that the Sacubitril/Valsartan (Sac/Val) can improve kidney function, and the disordered gut microbiota and part of its metabolites are related to the development of DKD. Therefore, we aim to explore whether the effect of Sac/Val on DKD is associated with the gut microbiota and related plasma metabolic profiles.MethodsMale C57BL/6J mice were randomly divided into 3 groups: Con group (n = 5), DKD group (n = 6), and Sac/Val group (n = 6) . Sac/Val group was treated with Sac/Val solution. The intervention was given once every 2 days for 6 weeks. We measured the blood glucose and urine protein level of mice at different times. We then collected samples at the end of experiment for the 16s rRNA gene sequencing analysis and the untargeted plasma metabonomic analysis.ResultsWe found that the plasma creatinine concentration of DKD-group mice was significantly higher than that of Con-group mice, whereas it was reduced after the Sac/Val treatment. Compared with DKD mice, Sac/Val treatment could decrease the expression of indicators related to EndMT and renal fibrosis like vimentin, collagen IV and fibronectin in kidney. According to the criteria of LDA ≥ 2.5 and p<0.05, LefSe analysis of gut microbiota identified 13 biomarkers in Con group, and 33 biomarkers in DKD group, mainly including Prevotella, Escherichia_Shigella and Christensenellaceae_R_7_group, etc. For the Sac/Val group, there were 21 biomarkers, such as Bacteroides, Rikenellaceae_RC9_gut_group, Parabacteroides, Lactobacillus, etc. Plasma metabolomics analysis identified a total of 648 metabolites, and 167 important differential metabolites were screened among groups. KEGG pathway of tryptophan metabolism: M and bile secretion: OS had the highest significance of enrichment.ConclusionsSac/Val improves the renal function of DKD mice by inhibiting renal fibrosis. This drug can also regulate gut microbiota in DKD mice.https://www.frontiersin.org/articles/10.3389/fendo.2022.1034818/fullsacubitril/valsartandiabetic kidney diseasegut microbiotametabolomemice |
| spellingShingle | Peipei Wang Peipei Wang Ruixue Guo Ruixue Guo Xiwen Bai Wen Cui Wen Cui Yiding Zhang Yiding Zhang Huangmin Li Huangmin Li Jin Shang Jin Shang Jin Shang Zhanzheng Zhao Zhanzheng Zhao Zhanzheng Zhao Sacubitril/Valsartan contributes to improving the diabetic kidney disease and regulating the gut microbiota in mice Frontiers in Endocrinology sacubitril/valsartan diabetic kidney disease gut microbiota metabolome mice |
| title | Sacubitril/Valsartan contributes to improving the diabetic kidney disease and regulating the gut microbiota in mice |
| title_full | Sacubitril/Valsartan contributes to improving the diabetic kidney disease and regulating the gut microbiota in mice |
| title_fullStr | Sacubitril/Valsartan contributes to improving the diabetic kidney disease and regulating the gut microbiota in mice |
| title_full_unstemmed | Sacubitril/Valsartan contributes to improving the diabetic kidney disease and regulating the gut microbiota in mice |
| title_short | Sacubitril/Valsartan contributes to improving the diabetic kidney disease and regulating the gut microbiota in mice |
| title_sort | sacubitril valsartan contributes to improving the diabetic kidney disease and regulating the gut microbiota in mice |
| topic | sacubitril/valsartan diabetic kidney disease gut microbiota metabolome mice |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2022.1034818/full |
| work_keys_str_mv | AT peipeiwang sacubitrilvalsartancontributestoimprovingthediabetickidneydiseaseandregulatingthegutmicrobiotainmice AT peipeiwang sacubitrilvalsartancontributestoimprovingthediabetickidneydiseaseandregulatingthegutmicrobiotainmice AT ruixueguo sacubitrilvalsartancontributestoimprovingthediabetickidneydiseaseandregulatingthegutmicrobiotainmice AT ruixueguo sacubitrilvalsartancontributestoimprovingthediabetickidneydiseaseandregulatingthegutmicrobiotainmice AT xiwenbai sacubitrilvalsartancontributestoimprovingthediabetickidneydiseaseandregulatingthegutmicrobiotainmice AT wencui sacubitrilvalsartancontributestoimprovingthediabetickidneydiseaseandregulatingthegutmicrobiotainmice AT wencui sacubitrilvalsartancontributestoimprovingthediabetickidneydiseaseandregulatingthegutmicrobiotainmice AT yidingzhang sacubitrilvalsartancontributestoimprovingthediabetickidneydiseaseandregulatingthegutmicrobiotainmice AT yidingzhang sacubitrilvalsartancontributestoimprovingthediabetickidneydiseaseandregulatingthegutmicrobiotainmice AT huangminli sacubitrilvalsartancontributestoimprovingthediabetickidneydiseaseandregulatingthegutmicrobiotainmice AT huangminli sacubitrilvalsartancontributestoimprovingthediabetickidneydiseaseandregulatingthegutmicrobiotainmice AT jinshang sacubitrilvalsartancontributestoimprovingthediabetickidneydiseaseandregulatingthegutmicrobiotainmice AT jinshang sacubitrilvalsartancontributestoimprovingthediabetickidneydiseaseandregulatingthegutmicrobiotainmice AT jinshang sacubitrilvalsartancontributestoimprovingthediabetickidneydiseaseandregulatingthegutmicrobiotainmice AT zhanzhengzhao sacubitrilvalsartancontributestoimprovingthediabetickidneydiseaseandregulatingthegutmicrobiotainmice AT zhanzhengzhao sacubitrilvalsartancontributestoimprovingthediabetickidneydiseaseandregulatingthegutmicrobiotainmice AT zhanzhengzhao sacubitrilvalsartancontributestoimprovingthediabetickidneydiseaseandregulatingthegutmicrobiotainmice |