Multiomics Assessment of the Gut Microbiome in Rare Hyperoxaluric Conditions

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

doi:10.1016/j.ekir.2024.03.004

Multiomics Assessment of the Gut Microbiome in Rare Hyperoxaluric Conditions

Kidney Int Rep. 2024 Mar 11;9(6):1836-1848. doi: 10.1016/j.ekir.2024.03.004. eCollection 2024 Jun.

Authors

Nadim Zaidan¹, Chan Wang², Ze Chen², John C Lieske^{3

4}, Dawn Milliner³, Barbara Seide³, Melody Ho¹, Huilin Li², Kelly V Ruggles⁵, Frank Modersitzki¹, David S Goldfarb¹, Martin Blaser⁶, Lama Nazzal¹

Affiliations

¹ Department of Medicine, Division of Nephrology, NYU Langone Medical Center, New York, New York, USA.
² Department of Population Health, New York University School of Medicine, NYU Langone Health, New York, New York, USA.
³ Department of Internal Medicine, Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, USA.
⁴ Department of Laboratory Medicine, Mayo Clinic, Rochester, Minnesota, USA.
⁵ Department of Medicine, Division of Precision Medicine, New York University School of Medicine, NYU Langone Health, New York, New York, USA.
⁶ Center for Advanced Biotechnology and Medicine, Rutgers University, Piscataway, New Jersey, USA.

Abstract

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.

Keywords: hyperoxaluria; kidney stones; microbiome; multiomics; oxalate.

Abstract

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