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 its oxalate-degrading enzyme activity. In this cross-sectional study, we leverage multi-omics 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 I 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 and metatranscriptomic 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 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- 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. Metatranscriptomic-based network analysis identified the most interactive bacterial network in PH patients. EH patients 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.