Multiomics Assessment of the Gut Microbiome in Rare Hyperoxaluric Conditions
Introduction: Hyperoxaluria is a risk factor for kidney stone formation and chronic kidney disease progression. The microbiome is an important protective factor against oxalate accumulation through the activity of its oxalate-degrading enzymes (ODEs). In this cross-sectional study, we leverage multi...
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Elsevier
2024-06-01
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| Series: | Kidney International Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2468024924015468 |
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| author | Nadim Zaidan Chan Wang Ze Chen John C. Lieske Dawn Milliner Barbara Seide Melody Ho Huilin Li Kelly V. Ruggles Frank Modersitzki David S. Goldfarb Martin Blaser Lama Nazzal |
| author_facet | Nadim Zaidan Chan Wang Ze Chen John C. Lieske Dawn Milliner Barbara Seide Melody Ho Huilin Li Kelly V. Ruggles Frank Modersitzki David S. Goldfarb Martin Blaser Lama Nazzal |
| author_sort | Nadim Zaidan |
| collection | DOAJ |
| description | Introduction: Hyperoxaluria is a risk factor for kidney stone formation and chronic kidney disease progression. The microbiome is an important protective factor against oxalate accumulation through the activity of its oxalate-degrading enzymes (ODEs). In this cross-sectional study, we leverage multiomics to characterize the microbial community of participants with primary and enteric hyperoxaluria, as well as idiopathic calcium oxalate kidney stone (CKS) formers, focusing on the relationship between oxalate degrading functions of the microbiome. Methods: Patients diagnosed with type 1 primary hyperoxaluria (PH), enteric hyperoxaluria (EH), and CKS were screened for inclusion in the study. Participants completed a food frequency questionnaire recording their dietary oxalate content while fecal oxalate levels were ascertained. DNA and RNA were extracted from stool samples and sequenced. Metagenomic (MTG) and metatranscriptomic (MTT) data were processed through our bioinformatics pipelines, and microbiome diversity, differential abundance, and networks were subject to statistical analysis in relationship with oxalate levels. Results: A total of 38 subjects were recruited, including 13 healthy participants, 12 patients with recurrent CKS, 8 with PH, and 5 with EH. Urinary and fecal oxalate were significantly higher in the PH and the EH population compared to healthy controls. At the community level, alpha-diversity and beta-diversity indices were similar across all populations. The respective contributions of single bacterial species to the total oxalate degradative potential were similar in healthy and PH subjects. MTT-based network analysis identified the most interactive bacterial network in patients with PH. Patients with EH had a decreased abundance of multiple major oxalate degraders. Conclusion: The composition and inferred activity of oxalate-degrading microbiota were differentially associated with host clinical conditions. Identifying these changes improves our understanding of the relationships between dietary constituents, microbiota, and oxalate homeostasis, and suggests new therapeutic approaches protecting against hyperoxaluria. |
| format | Article |
| id | doaj-art-212142a00aae4bcf88536789d06cddd2 |
| institution | Kabale University |
| issn | 2468-0249 |
| language | English |
| publishDate | 2024-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Kidney International Reports |
| spelling | doaj-art-212142a00aae4bcf88536789d06cddd22025-08-20T03:25:53ZengElsevierKidney International Reports2468-02492024-06-01961836184810.1016/j.ekir.2024.03.004Multiomics Assessment of the Gut Microbiome in Rare Hyperoxaluric ConditionsNadim Zaidan0Chan Wang1Ze Chen2John C. Lieske3Dawn Milliner4Barbara Seide5Melody Ho6Huilin Li7Kelly V. Ruggles8Frank Modersitzki9David S. Goldfarb10Martin Blaser11Lama Nazzal12Department of Medicine, Division of Nephrology, NYU Langone Medical Center, New York, New York, USADepartment of Population Health, New York University School of Medicine, NYU Langone Health, New York, New York, USADepartment of Population Health, New York University School of Medicine, NYU Langone Health, New York, New York, USADepartment of Internal Medicine, Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, USA; Department of Laboratory Medicine, Mayo Clinic, Rochester, Minnesota, USADepartment of Internal Medicine, Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, USADepartment of Internal Medicine, Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, USADepartment of Medicine, Division of Nephrology, NYU Langone Medical Center, New York, New York, USADepartment of Population Health, New York University School of Medicine, NYU Langone Health, New York, New York, USADepartment of Medicine, Division of Precision Medicine, New York University School of Medicine, NYU Langone Health, New York, New York, USADepartment of Medicine, Division of Nephrology, NYU Langone Medical Center, New York, New York, USADepartment of Medicine, Division of Nephrology, NYU Langone Medical Center, New York, New York, USACenter for Advanced Biotechnology and Medicine, Rutgers University, Piscataway, New Jersey, USADepartment of Medicine, Division of Nephrology, NYU Langone Medical Center, New York, New York, USA; Correspondence: Lama Nazzal, NYU Langone Medical Center Department of Medicine, 550 1st Avenue, New York, New York 10016, USA.Introduction: Hyperoxaluria is a risk factor for kidney stone formation and chronic kidney disease progression. The microbiome is an important protective factor against oxalate accumulation through the activity of its oxalate-degrading enzymes (ODEs). In this cross-sectional study, we leverage multiomics to characterize the microbial community of participants with primary and enteric hyperoxaluria, as well as idiopathic calcium oxalate kidney stone (CKS) formers, focusing on the relationship between oxalate degrading functions of the microbiome. Methods: Patients diagnosed with type 1 primary hyperoxaluria (PH), enteric hyperoxaluria (EH), and CKS were screened for inclusion in the study. Participants completed a food frequency questionnaire recording their dietary oxalate content while fecal oxalate levels were ascertained. DNA and RNA were extracted from stool samples and sequenced. Metagenomic (MTG) and metatranscriptomic (MTT) data were processed through our bioinformatics pipelines, and microbiome diversity, differential abundance, and networks were subject to statistical analysis in relationship with oxalate levels. Results: A total of 38 subjects were recruited, including 13 healthy participants, 12 patients with recurrent CKS, 8 with PH, and 5 with EH. Urinary and fecal oxalate were significantly higher in the PH and the EH population compared to healthy controls. At the community level, alpha-diversity and beta-diversity indices were similar across all populations. The respective contributions of single bacterial species to the total oxalate degradative potential were similar in healthy and PH subjects. MTT-based network analysis identified the most interactive bacterial network in patients with PH. Patients with EH had a decreased abundance of multiple major oxalate degraders. Conclusion: The composition and inferred activity of oxalate-degrading microbiota were differentially associated with host clinical conditions. Identifying these changes improves our understanding of the relationships between dietary constituents, microbiota, and oxalate homeostasis, and suggests new therapeutic approaches protecting against hyperoxaluria.http://www.sciencedirect.com/science/article/pii/S2468024924015468hyperoxaluriakidney stonesmicrobiomemultiomicsoxalate |
| spellingShingle | Nadim Zaidan Chan Wang Ze Chen John C. Lieske Dawn Milliner Barbara Seide Melody Ho Huilin Li Kelly V. Ruggles Frank Modersitzki David S. Goldfarb Martin Blaser Lama Nazzal Multiomics Assessment of the Gut Microbiome in Rare Hyperoxaluric Conditions Kidney International Reports hyperoxaluria kidney stones microbiome multiomics oxalate |
| title | Multiomics Assessment of the Gut Microbiome in Rare Hyperoxaluric Conditions |
| title_full | Multiomics Assessment of the Gut Microbiome in Rare Hyperoxaluric Conditions |
| title_fullStr | Multiomics Assessment of the Gut Microbiome in Rare Hyperoxaluric Conditions |
| title_full_unstemmed | Multiomics Assessment of the Gut Microbiome in Rare Hyperoxaluric Conditions |
| title_short | Multiomics Assessment of the Gut Microbiome in Rare Hyperoxaluric Conditions |
| title_sort | multiomics assessment of the gut microbiome in rare hyperoxaluric conditions |
| topic | hyperoxaluria kidney stones microbiome multiomics oxalate |
| url | http://www.sciencedirect.com/science/article/pii/S2468024924015468 |
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