关键词: hyperoxaluria kidney stones microbiome multiomics oxalate

来  源:   DOI:10.1016/j.ekir.2024.03.004   PDF(Pubmed)

Abstract:
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
摘要:
高草酸尿症是肾结石形成和慢性肾脏疾病进展的危险因素。微生物组是通过其草酸盐降解酶(ODE)的活性抵抗草酸盐积累的重要保护因子。在这项横断面研究中,我们利用多组学来表征患有原发性和肠道高草酸尿症的参与者的微生物群落,以及特发性草酸钙肾结石(CKS)形成者,重点研究了草酸盐降解微生物组功能之间的关系。
被诊断为1型原发性高尿毒症(PH)的患者,肠道高草酸尿症(EH),和CKS被筛选纳入研究。参与者完成了食物频率问卷,记录了他们的饮食草酸盐含量,同时确定了粪便草酸盐水平。从粪便样品中提取DNA和RNA并测序。通过我们的生物信息学管道处理宏基因组(MTG)和meta转录组(MTT)数据,微生物多样性,差异丰度,和网络与草酸盐水平的关系进行统计分析。
共招募了38名受试者,包括13名健康参与者,12例复发性CKS,8与PH,5与EH与健康对照组相比,PH和EH人群中的尿和粪便草酸盐明显更高。在社区层面,所有种群的α-多样性和β-多样性指数相似。在健康和PH受试者中,单个细菌物种对总草酸盐降解潜力的贡献相似。基于MTT的网络分析确定了PH患者中最具交互性的细菌网络。EH患者的多种主要草酸盐降解物的丰度降低。
降解草酸盐的微生物群的组成和推断的活性与宿主临床状况差异相关。识别这些变化可以提高我们对饮食成分之间关系的理解,微生物群,和草酸盐稳态,并提出了新的治疗方法来预防高草酸尿。
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