Integrative metagenomic and metabolomic analyses reveal the role of gut microbiota in antibody-mediated renal allograft rejection
Abstract Background Antibody-mediated rejection (AMR) remains one of the major barriers for graft survival after kidney transplantation. Our previous study suggested a gut microbiota dysbiosis in kidney transplantation recipients with AMR. However, alternations in gut microbial function and structur...
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| Format: | Article |
| Language: | English |
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BMC
2022-12-01
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| Series: | Journal of Translational Medicine |
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| Online Access: | https://doi.org/10.1186/s12967-022-03825-6 |
| _version_ | 1797977257738764288 |
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| author | Xin Li Ruoying Li Bingqing Ji Lili Zhao Junpeng Wang Tianzhong Yan |
| author_facet | Xin Li Ruoying Li Bingqing Ji Lili Zhao Junpeng Wang Tianzhong Yan |
| author_sort | Xin Li |
| collection | DOAJ |
| description | Abstract Background Antibody-mediated rejection (AMR) remains one of the major barriers for graft survival after kidney transplantation. Our previous study suggested a gut microbiota dysbiosis in kidney transplantation recipients with AMR. However, alternations in gut microbial function and structure at species level have not been identified. In the present study, we investigated the metagenomic and metabolic patterns of gut microbiota in AMR patients to provide a comprehensive and in-depth understanding of gut microbiota dysbiosis in AMR. Methods We enrolled 60 kidney transplantation recipients, 28 showed AMR and 32 were non-AMR controls with stable post-transplant renal functions. Shotgun sequencing and untargeted LC/MS metabolomic profiling of fecal samples were performed in kidney transplantation recipients with AMR and controls. Results Totally, we identified 311 down-regulated and 27 up-regulated gut microbial species associated with AMR after kidney transplantation, resulting in the altered expression levels of 437 genes enriched in 22 pathways, of which 13 were related to metabolism. Moreover, 32 differential fecal metabolites were found in recipients with AMR. Among them, alterations in 3b-hydroxy-5-cholenoic acid, l-pipecolic acid, taurocholate, and 6k-PGF1alpha-d4 directly correlated with changes in gut microbial species and functions. Specific differential fecal species and metabolites were strongly associated with clinical indexes (Cr, BUN, etc.), and could distinguish the recipients with AMR from controls as potential biomarkers. Conclusions Altogether, our findings provided a comprehensive and in-depth understanding of the correlation between AMR and gut microbiota, which is important for the etiological and diagnostic study of AMR after kidney transplantation. |
| first_indexed | 2024-04-11T05:04:07Z |
| format | Article |
| id | doaj.art-5729dfa4e9b5405a8397111b08cf978b |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-04-11T05:04:07Z |
| publishDate | 2022-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-5729dfa4e9b5405a8397111b08cf978b2022-12-25T12:27:22ZengBMCJournal of Translational Medicine1479-58762022-12-0120111410.1186/s12967-022-03825-6Integrative metagenomic and metabolomic analyses reveal the role of gut microbiota in antibody-mediated renal allograft rejectionXin Li0Ruoying Li1Bingqing Ji2Lili Zhao3Junpeng Wang4Tianzhong Yan5Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou UniversityDepartment of Pathophysiology, School of Basic Medical Sciences, Zhengzhou UniversityDepartment of Urology, Henan Provincial People’s Hospital, Zhengzhou University People’s Hospital, Henan University People’s HospitalDepartment of Pathophysiology, School of Basic Medical Sciences, Zhengzhou UniversityDepartment of Urology, Henan Provincial People’s Hospital, Zhengzhou University People’s Hospital, Henan University People’s HospitalDepartment of Urology, Henan Provincial People’s Hospital, Zhengzhou University People’s Hospital, Henan University People’s HospitalAbstract Background Antibody-mediated rejection (AMR) remains one of the major barriers for graft survival after kidney transplantation. Our previous study suggested a gut microbiota dysbiosis in kidney transplantation recipients with AMR. However, alternations in gut microbial function and structure at species level have not been identified. In the present study, we investigated the metagenomic and metabolic patterns of gut microbiota in AMR patients to provide a comprehensive and in-depth understanding of gut microbiota dysbiosis in AMR. Methods We enrolled 60 kidney transplantation recipients, 28 showed AMR and 32 were non-AMR controls with stable post-transplant renal functions. Shotgun sequencing and untargeted LC/MS metabolomic profiling of fecal samples were performed in kidney transplantation recipients with AMR and controls. Results Totally, we identified 311 down-regulated and 27 up-regulated gut microbial species associated with AMR after kidney transplantation, resulting in the altered expression levels of 437 genes enriched in 22 pathways, of which 13 were related to metabolism. Moreover, 32 differential fecal metabolites were found in recipients with AMR. Among them, alterations in 3b-hydroxy-5-cholenoic acid, l-pipecolic acid, taurocholate, and 6k-PGF1alpha-d4 directly correlated with changes in gut microbial species and functions. Specific differential fecal species and metabolites were strongly associated with clinical indexes (Cr, BUN, etc.), and could distinguish the recipients with AMR from controls as potential biomarkers. Conclusions Altogether, our findings provided a comprehensive and in-depth understanding of the correlation between AMR and gut microbiota, which is important for the etiological and diagnostic study of AMR after kidney transplantation.https://doi.org/10.1186/s12967-022-03825-6Antibody-mediated rejectionGut microbiotaMetagenomicsFecal metabolitesKidney transplantation |
| spellingShingle | Xin Li Ruoying Li Bingqing Ji Lili Zhao Junpeng Wang Tianzhong Yan Integrative metagenomic and metabolomic analyses reveal the role of gut microbiota in antibody-mediated renal allograft rejection Journal of Translational Medicine Antibody-mediated rejection Gut microbiota Metagenomics Fecal metabolites Kidney transplantation |
| title | Integrative metagenomic and metabolomic analyses reveal the role of gut microbiota in antibody-mediated renal allograft rejection |
| title_full | Integrative metagenomic and metabolomic analyses reveal the role of gut microbiota in antibody-mediated renal allograft rejection |
| title_fullStr | Integrative metagenomic and metabolomic analyses reveal the role of gut microbiota in antibody-mediated renal allograft rejection |
| title_full_unstemmed | Integrative metagenomic and metabolomic analyses reveal the role of gut microbiota in antibody-mediated renal allograft rejection |
| title_short | Integrative metagenomic and metabolomic analyses reveal the role of gut microbiota in antibody-mediated renal allograft rejection |
| title_sort | integrative metagenomic and metabolomic analyses reveal the role of gut microbiota in antibody mediated renal allograft rejection |
| topic | Antibody-mediated rejection Gut microbiota Metagenomics Fecal metabolites Kidney transplantation |
| url | https://doi.org/10.1186/s12967-022-03825-6 |
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