Alterations in the gut microbiome and metabolism profiles reveal the possible molecular mechanism of renal injury induced by hyperuricemia in a mouse model of renal insufficiency
Objectives: To investigate the role of the intestinal flora and metabolites in the development of hyperuricemic renal injury in chronic kidney disease (CKD).Methods: Unilaterally nephrectomized mice were fed with adenine and potassium oxonate for 9 weeks. HE staining combined with plasma biochemical...
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| Format: | Article |
| Language: | English |
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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.2024.2387429 |
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| author | Ping Liu Jianli Yang Meiping Jin Ping Hu Yifan Zhu Yuyan Tang Yu Chen Xudong Xu Haidong He |
| author_facet | Ping Liu Jianli Yang Meiping Jin Ping Hu Yifan Zhu Yuyan Tang Yu Chen Xudong Xu Haidong He |
| author_sort | Ping Liu |
| collection | DOAJ |
| description | Objectives: To investigate the role of the intestinal flora and metabolites in the development of hyperuricemic renal injury in chronic kidney disease (CKD).Methods: Unilaterally nephrectomized mice were fed with adenine and potassium oxonate for 9 weeks. HE staining combined with plasma biochemical indicators was used to evaluate renal pathological and functional changes. We conducted 16S rRNA sequencing and untargeted metabolomics on feces and plasma samples to reveale changes in intestinal microbiota and metabolites.Result: Our analysis revealed significant differences in 15 bacterial genera, with 7 being upregulated and 8 being downregulated. Furthermore, metabolomic analysis revealed changes in the distribution of amino acid and biotin metabolites in basic metabolic pathways in both feces and serum. Specifically, differentially abundant metabolites in feces were associated primarily with histidine metabolism; the biosynthesis of phenylalanine, tyrosine, and tryptophan; and tyrosine metabolism. In plasma, the differentially abundant metabolites were involved in multiple metabolic pathways, including aminoacyl-tRNA biosynthesis; glycine, serine, and threonine amino acid metabolism; valine, leucine, and isoleucine biosynthesis; tyrosine biosynthesis and metabolism; biotin metabolism; and taurine and hypotaurine metabolism. Furthermore, correlation analysis revealed that Akkermansia, UCG-005, Lachnospiraceae_NK4A136_group, Lactococcus, and Butymonas were associated with various differentially abundant metabolites as well as renal function, oxidative stress, and mitophagy. The changes in the intestinal flora observed in hyperuricemia may lead to imbalances in amino acid and biotin metabolism in both the intestine and host, ultimately affecting oxidative stress and mitophagy in mice and accelerating the progression of CKD.Conclusion: Our findings provide insights into a potential pathogenic mechanism by which hyperuricemia exacerbates renal injury in mice with renal insufficiency. Understanding these pathways may offer new therapeutic strategies for managing hyperuricemic renal injury in CKD patients. |
| format | Article |
| id | doaj-art-3545b34ecb51438f90cede4bb379fbc8 |
| institution | DOAJ |
| issn | 0886-022X 1525-6049 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Renal Failure |
| spelling | doaj-art-3545b34ecb51438f90cede4bb379fbc82025-08-20T03:12:51ZengTaylor & Francis GroupRenal Failure0886-022X1525-60492024-12-0146210.1080/0886022X.2024.2387429Alterations in the gut microbiome and metabolism profiles reveal the possible molecular mechanism of renal injury induced by hyperuricemia in a mouse model of renal insufficiencyPing Liu0Jianli Yang1Meiping Jin2Ping Hu3Yifan Zhu4Yuyan Tang5Yu Chen6Xudong Xu7Haidong He8Division of Nephrology, Minhang Hospital, Fudan University, Shanghai, ChinaEast China University of Science and Technology, Shanghai, ChinaDivision of Nephrology, Minhang Hospital, Fudan University, Shanghai, ChinaDivision of Nephrology, Minhang Hospital, Fudan University, Shanghai, ChinaDivision of Nephrology, Minhang Hospital, Fudan University, Shanghai, ChinaDivision of Nephrology, Minhang Hospital, Fudan University, Shanghai, ChinaEast China University of Science and Technology, Shanghai, ChinaDivision of Nephrology, Minhang Hospital, Fudan University, Shanghai, ChinaDivision of Nephrology, Minhang Hospital, Fudan University, Shanghai, ChinaObjectives: To investigate the role of the intestinal flora and metabolites in the development of hyperuricemic renal injury in chronic kidney disease (CKD).Methods: Unilaterally nephrectomized mice were fed with adenine and potassium oxonate for 9 weeks. HE staining combined with plasma biochemical indicators was used to evaluate renal pathological and functional changes. We conducted 16S rRNA sequencing and untargeted metabolomics on feces and plasma samples to reveale changes in intestinal microbiota and metabolites.Result: Our analysis revealed significant differences in 15 bacterial genera, with 7 being upregulated and 8 being downregulated. Furthermore, metabolomic analysis revealed changes in the distribution of amino acid and biotin metabolites in basic metabolic pathways in both feces and serum. Specifically, differentially abundant metabolites in feces were associated primarily with histidine metabolism; the biosynthesis of phenylalanine, tyrosine, and tryptophan; and tyrosine metabolism. In plasma, the differentially abundant metabolites were involved in multiple metabolic pathways, including aminoacyl-tRNA biosynthesis; glycine, serine, and threonine amino acid metabolism; valine, leucine, and isoleucine biosynthesis; tyrosine biosynthesis and metabolism; biotin metabolism; and taurine and hypotaurine metabolism. Furthermore, correlation analysis revealed that Akkermansia, UCG-005, Lachnospiraceae_NK4A136_group, Lactococcus, and Butymonas were associated with various differentially abundant metabolites as well as renal function, oxidative stress, and mitophagy. The changes in the intestinal flora observed in hyperuricemia may lead to imbalances in amino acid and biotin metabolism in both the intestine and host, ultimately affecting oxidative stress and mitophagy in mice and accelerating the progression of CKD.Conclusion: Our findings provide insights into a potential pathogenic mechanism by which hyperuricemia exacerbates renal injury in mice with renal insufficiency. Understanding these pathways may offer new therapeutic strategies for managing hyperuricemic renal injury in CKD patients.https://www.tandfonline.com/doi/10.1080/0886022X.2024.2387429Chronic kidney diseasehyperuricemiarenal injurygut microbiotametabolism profiling |
| spellingShingle | Ping Liu Jianli Yang Meiping Jin Ping Hu Yifan Zhu Yuyan Tang Yu Chen Xudong Xu Haidong He Alterations in the gut microbiome and metabolism profiles reveal the possible molecular mechanism of renal injury induced by hyperuricemia in a mouse model of renal insufficiency Renal Failure Chronic kidney disease hyperuricemia renal injury gut microbiota metabolism profiling |
| title | Alterations in the gut microbiome and metabolism profiles reveal the possible molecular mechanism of renal injury induced by hyperuricemia in a mouse model of renal insufficiency |
| title_full | Alterations in the gut microbiome and metabolism profiles reveal the possible molecular mechanism of renal injury induced by hyperuricemia in a mouse model of renal insufficiency |
| title_fullStr | Alterations in the gut microbiome and metabolism profiles reveal the possible molecular mechanism of renal injury induced by hyperuricemia in a mouse model of renal insufficiency |
| title_full_unstemmed | Alterations in the gut microbiome and metabolism profiles reveal the possible molecular mechanism of renal injury induced by hyperuricemia in a mouse model of renal insufficiency |
| title_short | Alterations in the gut microbiome and metabolism profiles reveal the possible molecular mechanism of renal injury induced by hyperuricemia in a mouse model of renal insufficiency |
| title_sort | alterations in the gut microbiome and metabolism profiles reveal the possible molecular mechanism of renal injury induced by hyperuricemia in a mouse model of renal insufficiency |
| topic | Chronic kidney disease hyperuricemia renal injury gut microbiota metabolism profiling |
| url | https://www.tandfonline.com/doi/10.1080/0886022X.2024.2387429 |
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