Dynamic gut microbiome-metabolome in cationic bovine serum albumin induced experimental immune-complex glomerulonephritis and effect of losartan and mycophenolate mofetil on microbiota modulation
Dynamic changes in gut dysbiosis and metabolomic dysregulation are associated with immune-complex glomerulonephritis (ICGN). However, an in-depth study on this topic is currently lacking. Herein, we report an ICGN model to address this gap. ICGN was induced via the intravenous injection of cationize...
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Elsevier
2024-04-01
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| Series: | Journal of Pharmaceutical Analysis |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2095177923003040 |
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| author | Wenying Shi Zhaojun Li Weida Wang Xikun Liu Haijie Wu Xiaoguang Chen Xunrong Zhou Sen Zhang |
| author_facet | Wenying Shi Zhaojun Li Weida Wang Xikun Liu Haijie Wu Xiaoguang Chen Xunrong Zhou Sen Zhang |
| author_sort | Wenying Shi |
| collection | DOAJ |
| description | Dynamic changes in gut dysbiosis and metabolomic dysregulation are associated with immune-complex glomerulonephritis (ICGN). However, an in-depth study on this topic is currently lacking. Herein, we report an ICGN model to address this gap. ICGN was induced via the intravenous injection of cationized bovine serum albumin (c-BSA) into Sprague-Dawley (SD) rats for two weeks, after which mycophenolate mofetil (MMF) and losartan were administered orally. Two and six weeks after ICGN establishment, fecal samples were collected and 16S ribosomal DNA (rDNA) sequencing and untargeted metabolomic were conducted. Fecal microbiota transplantation (FMT) was conducted to determine whether gut normalization caused by MMF and losartan contributed to their renal protective effects. A gradual decline in microbial diversity and richness was accompanied by a loss of renal function. Approximately 18 genera were found to have significantly different relative abundances between the early and later stages, and Marvinbryantia and Allobaculum were markedly upregulated in both stages. Untargeted metabolomics indicated that the tryptophan metabolism was enhanced in ICGN, characterized by the overproduction of indole and kynurenic acid, while the serotonin pathway was reduced. Administration of losartan and MMF ameliorated microbial dysbiosis and reduced the accumulation of indoxyl conjugates in feces. FMT using feces from animals administered MMF and losartan improved gut dysbiosis by decreasing the Firmicutes/Bacteroidetes (F/B) ratio but did not improve renal function. These findings indicate that ICGN induces serous gut dysbiosis, wherein an altered tryptophan metabolism may contribute to its progression. MMF and losartan significantly reversed the gut microbial and metabolomic dysbiosis, which partially contributed to their renoprotective effects. |
| first_indexed | 2024-04-24T07:38:52Z |
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| id | doaj.art-928fab7cad91405fa488bc0a7df59a26 |
| institution | Directory Open Access Journal |
| issn | 2095-1779 |
| language | English |
| last_indexed | 2024-04-24T07:38:52Z |
| publishDate | 2024-04-01 |
| publisher | Elsevier |
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| series | Journal of Pharmaceutical Analysis |
| spelling | doaj.art-928fab7cad91405fa488bc0a7df59a262024-04-20T04:17:19ZengElsevierJournal of Pharmaceutical Analysis2095-17792024-04-01144100931Dynamic gut microbiome-metabolome in cationic bovine serum albumin induced experimental immune-complex glomerulonephritis and effect of losartan and mycophenolate mofetil on microbiota modulationWenying Shi0Zhaojun Li1Weida Wang2Xikun Liu3Haijie Wu4Xiaoguang Chen5Xunrong Zhou6Sen Zhang7State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China; State Key Laboratory of Functions and Applications of Medicinal Plants, College of Pharmacy, Guizhou Provincial Engineering Technology Research Center for Chemical Drug R&D, Guizhou Medical University, Guiyang, 550004, ChinaState Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China; Department of Medicine Solna, Center for Molecular Medicine, Karolinska University Hospital and Karolinska Institute, Stockholm, 17176, SwedenState Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, ChinaState Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, ChinaState Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, ChinaState Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, ChinaDepartment of Pharmacy, The Second Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, 550001, China; Corresponding author.State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China; Corresponding author.Dynamic changes in gut dysbiosis and metabolomic dysregulation are associated with immune-complex glomerulonephritis (ICGN). However, an in-depth study on this topic is currently lacking. Herein, we report an ICGN model to address this gap. ICGN was induced via the intravenous injection of cationized bovine serum albumin (c-BSA) into Sprague-Dawley (SD) rats for two weeks, after which mycophenolate mofetil (MMF) and losartan were administered orally. Two and six weeks after ICGN establishment, fecal samples were collected and 16S ribosomal DNA (rDNA) sequencing and untargeted metabolomic were conducted. Fecal microbiota transplantation (FMT) was conducted to determine whether gut normalization caused by MMF and losartan contributed to their renal protective effects. A gradual decline in microbial diversity and richness was accompanied by a loss of renal function. Approximately 18 genera were found to have significantly different relative abundances between the early and later stages, and Marvinbryantia and Allobaculum were markedly upregulated in both stages. Untargeted metabolomics indicated that the tryptophan metabolism was enhanced in ICGN, characterized by the overproduction of indole and kynurenic acid, while the serotonin pathway was reduced. Administration of losartan and MMF ameliorated microbial dysbiosis and reduced the accumulation of indoxyl conjugates in feces. FMT using feces from animals administered MMF and losartan improved gut dysbiosis by decreasing the Firmicutes/Bacteroidetes (F/B) ratio but did not improve renal function. These findings indicate that ICGN induces serous gut dysbiosis, wherein an altered tryptophan metabolism may contribute to its progression. MMF and losartan significantly reversed the gut microbial and metabolomic dysbiosis, which partially contributed to their renoprotective effects.http://www.sciencedirect.com/science/article/pii/S2095177923003040Immune-complex glomerulonephritisGut microbiomeMetabolomicsFecal microbiota transplantTryptophan metabolism |
| spellingShingle | Wenying Shi Zhaojun Li Weida Wang Xikun Liu Haijie Wu Xiaoguang Chen Xunrong Zhou Sen Zhang Dynamic gut microbiome-metabolome in cationic bovine serum albumin induced experimental immune-complex glomerulonephritis and effect of losartan and mycophenolate mofetil on microbiota modulation Journal of Pharmaceutical Analysis Immune-complex glomerulonephritis Gut microbiome Metabolomics Fecal microbiota transplant Tryptophan metabolism |
| title | Dynamic gut microbiome-metabolome in cationic bovine serum albumin induced experimental immune-complex glomerulonephritis and effect of losartan and mycophenolate mofetil on microbiota modulation |
| title_full | Dynamic gut microbiome-metabolome in cationic bovine serum albumin induced experimental immune-complex glomerulonephritis and effect of losartan and mycophenolate mofetil on microbiota modulation |
| title_fullStr | Dynamic gut microbiome-metabolome in cationic bovine serum albumin induced experimental immune-complex glomerulonephritis and effect of losartan and mycophenolate mofetil on microbiota modulation |
| title_full_unstemmed | Dynamic gut microbiome-metabolome in cationic bovine serum albumin induced experimental immune-complex glomerulonephritis and effect of losartan and mycophenolate mofetil on microbiota modulation |
| title_short | Dynamic gut microbiome-metabolome in cationic bovine serum albumin induced experimental immune-complex glomerulonephritis and effect of losartan and mycophenolate mofetil on microbiota modulation |
| title_sort | dynamic gut microbiome metabolome in cationic bovine serum albumin induced experimental immune complex glomerulonephritis and effect of losartan and mycophenolate mofetil on microbiota modulation |
| topic | Immune-complex glomerulonephritis Gut microbiome Metabolomics Fecal microbiota transplant Tryptophan metabolism |
| url | http://www.sciencedirect.com/science/article/pii/S2095177923003040 |
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