Department of Nephrology, Zhongshan Hospital, Fudan University; Hemodialysis Quality Control Center of Shanghai; Shanghai Key Laboratory of Kidney and Blood Purification; Shanghai Institute for Kidney and Dialysis; Shanghai Clinical Medical Center for Kidney Disease, Shanghai, 200032, China.
Key Laboratory of Functional Dairy, Department of Nutrition and Health, China Agricultural University, Beijing, 100190, China.
Genome Biol. 2023 Oct 12;24(1):226. doi: 10.1186/s13059-023-03056-y.
The gut microbiota plays a crucial role in regulating host metabolism and producing uremic toxins in patients with end-stage renal disease (ESRD). Our objective is to advance toward a holistic understanding of the gut ecosystem and its functional capacity in such patients, which is still lacking.
Herein, we explore the gut microbiome of 378 hemodialytic ESRD patients and 290 healthy volunteers from two independent cohorts via deep metagenomic sequencing and metagenome-assembled-genome-based characterization of their feces. Our findings reveal fundamental alterations in the ESRD microbiome, characterized by a panel of 348 differentially abundant species, including ESRD-elevated representatives of Blautia spp., Dorea spp., and Eggerthellaceae, and ESRD-depleted Prevotella and Roseburia species. Through functional annotation of the ESRD-associated species, we uncover various taxon-specific functions linked to the disease, such as antimicrobial resistance, aromatic compound degradation, and biosynthesis of small bioactive molecules. Additionally, we show that the gut microbial composition can be utilized to predict serum uremic toxin concentrations, and based on this, we identify the key toxin-contributing species. Furthermore, our investigation extended to 47 additional non-dialyzed chronic kidney disease (CKD) patients, revealing a significant correlation between the abundance of ESRD-associated microbial signatures and CKD progression.
This study delineates the taxonomic and functional landscapes and biomarkers of the ESRD microbiome. Understanding the role of gut microbiota in ESRD could open new avenues for therapeutic interventions and personalized treatment approaches in patients with this condition.
肠道微生物群在调节宿主代谢和产生终末期肾病（ESRD）患者的尿毒症毒素方面发挥着关键作用。我们的目标是深入了解此类患者的肠道生态系统及其功能能力，而目前这方面的了解还很缺乏。
在此，我们通过深度宏基因组测序和粪便宏基因组组装基因组特征分析，研究了来自两个独立队列的 378 名血液透析 ESRD 患者和 290 名健康志愿者的肠道微生物组。我们的研究结果揭示了 ESRD 微生物组的基本改变，其特征是有 348 种差异丰度的物种，包括 Blautia spp.、Dorea spp.和 Eggerthellaceae 的 ESRD 升高代表物，以及 ESRD 减少的 Prevotella 和 Roseburia 物种。通过对与 ESRD 相关的物种进行功能注释，我们发现了与疾病相关的各种分类群特异性功能，如抗微生物耐药性、芳香化合物降解和小分子生物活性物质的生物合成。此外，我们表明肠道微生物组成可以用于预测血清尿毒症毒素浓度，并且在此基础上，我们确定了关键的毒素贡献物种。此外，我们的研究扩展到 47 名额外的非透析慢性肾病（CKD）患者，揭示了 ESRD 相关微生物特征的丰度与 CKD 进展之间存在显著相关性。
本研究描绘了 ESRD 微生物组的分类和功能图谱以及生物标志物。了解肠道微生物群在 ESRD 中的作用可能为该疾病患者的治疗干预和个性化治疗方法开辟新途径。
