DIFFERENCES IN GUT MICROBIOTA COMPOSITION ARE A KEY REASON FOR LOWER SERUM P-CRESOL SULFATE LEVELS IN PERITONEAL DIALYSIS PATIENTS COMPARED TO HEMODIALYSIS PATIENTS

 

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https://storage.unitedwebnetwork.com/files/1099/5aa9756d5032bc359e071527df5be0f5.pdf
DIFFERENCES IN GUT MICROBIOTA COMPOSITION ARE A KEY REASON FOR LOWER SERUM P-CRESOL SULFATE LEVELS IN PERITONEAL DIALYSIS PATIENTS COMPARED TO HEMODIALYSIS PATIENTS

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Shengzhuo
You
Min Lu luminous514@163.com Zhongshan Hospital Department of Nephrology Shanghai China -
Shulan Guo 15777167217@163.com Zhongshan Hospital Department of Nephrology Shanghai China -
Zhaoying Nie zyne0204@163.com Zhongshan Hospital Department of Nephrology Shanghai China -
Ji Ji anactive0103@163.com Zhongshan Hospital Department of Nephrology Shanghai China -
Yimei Wang wang.yimei@zs-hospital.sh.cn Zhongshan Hospital Department of Nephrology Shanghai China -
Xiaotian Jiang jiang.xiaotian@zs-hospital.sh.cn Zhongshan Hospital Department of Nephrology Shanghai China -
Lin Zhang zhang.lin2@zs-hospital.sh.cn Zhongshan Hospital Department of Nephrology Shanghai China -
Bo Xiang xiang.bo@zs-hospital.sh.cn Zhongshan Hospital Department of Nephrology Shanghai China -
Weiwei Wu wu.weiwei@zs-hospital.sh.cn Zhongshan Hospital Department of Nephrology Shanghai China -
Jun Ji ji.jun@zs-hospital.sh.cn Zhongshan Hospital Department of Nephrology Shanghai China -
Jianzhou Zou zou.jianzhou@zs-hospital.sh.cn Zhongshan Hospital Department of Nephrology Shanghai China -
Xiaoqiang Ding ding.xiaoqiang@zs-hospital.sh.cn Zhongshan Hospital Department of Nephrology Shanghai China -
Shengzhuo You youshengzhuo2001@163.com Zhongshan Hospital Department of Nephrology Shanghai China *
Xiaofang Yu yu.xiaofang@zs-hospital.sh.cn Zhongshan Hospital Department of Nephrology Shanghai China -
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Patients with end-stage kidney disease (ESKD) accumulate toxic metabolites that contribute to severe clinical complications. Peritoneal dialysis (PD) and hemodialysis (HD) exhibit distinct capacites for toxin clearance. Furthermore, the gut microbiota plays a significant role in toxin generation and is modulated by dialysis modality. This study aimed to compare gut microbiota composition and serum metabolite profiles between PD and HD patients, and to investigate their association with uremic toxin production.

This single-center, cross-sectional study included 100 ESKD patients (50 PD and 50 HD) matched for age, gender, and dialysis duration. Fecal and serum samples were collected and analyzed using 16S rRNA gene sequencing and non-targeted metabolomics. To validate the gut microbiota-serum metabolite relationship, fecal microbiota transplantation (FMT) was performed in germ-free CKD mice.

No significant differences in alpha diversity were observed between PD and HD groups, but beta diversity analysis revealed distinct gut microbial compositions, with PD patients showing higher abundance of opportunistic pathogens and lower abundance of beneficial bacteria. Non-targeted metabolomics identified 314 significantly different metabolites between the two groups, including significantly lower levels of p-cresyl sulfate (PCS) in PD patients, with altered metabolic pathways such as tyrosine, tryptophan, and phenylalanine metabolism. FMT experiments in CKD-induced germ-free mice confirmed higher serum PCS levels in HD recipients than in PD recipients, supporting the role of gut microbiota in toxin production.

PD and HD patients show distinct gut microbiota and serum metabolite profiles, with notably lower PCS levels in PD patients. These differences are partially mediated by gut microbiota variations. Modulating gut microbiota may represent a promising therapeutic approach to decrease uremic toxin production in dialysis patients.

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