Abstract: SA-PO744
Discovery and Validation of Intestinal Microbiota as Gut Biomarkers for Mirroring Disease Progression and Circulating Nephrotoxin Levels in CKD
Session Information
- CKD: Mechanisms - III
November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2103 CKD (Non-Dialysis): Mechanisms
Authors
- Wu, I-Wen, Chang Gung Memorial Hospital, Keelung, Taiwan
- Lin, Chan-Yu, Kidney Research Center, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan City, Taiwan
- Lai, Hsin-Chih, Chang Gung University, Taoyuan, Taiwan
- Su, Shih-Chi, Chang Gung Memorial Hospital, Keelung, Taiwan
Background
The interplay of the gut microbes with gut-producing nephrotoxins and the renal progression remains unclear in cohorts with different stage of chronic kidney disease (CKD) patients.
Methods
Analysis of intestinal microbiota (16S rRNA gene sequencing) and circulating p-cresyl sulfate/indoxyl sulfate were conducted in 92 (31 mild, 30 moderate and 31 advanced) CKD patients and 30 controls (discovery cohort), and further validated in a cohort comprising 22 controls and 76 peritoneal dialysis patients. Spearman’s correlation was used to determine the association of major genera (>0.1% abundance and present in >90% of samples) with serum biomarkers and disease severity. Chao1 index and Bray-Curtis distance were used to assess microbial community diversity. Functional composition of metagenomes was predicted from 16S rRNA data by the phylogenetic reconstruction of unobserved states (PICRUSt).
Results
Significant differences in bacterial composition and diversity were noted among controls and patients at different disease stages. A core CKD-associated microbiota consisted of 7 genera (Escherichia_Shigella, Dialister, Lachnospiraceae_ND3007_group, Pseudobutyrivibrio, Roseburia, Paraprevotella and Ruminiclostridium) and 2 species (Collinsella stercoris and Bacteroides eggerthii) were identified to be highly correlated with the stages of CKD. Paraprevotella, Pseudobutyrivibrio and Collinsella stercoris were superior in discriminating CKD from the controls than the use of urine protein/creatinine ratio, even at very early-stage of disease. The performance was further tested in validation cohort. Bacterial genera highly correlated with indoxyl sulfate and p-cresyl sulfate levels were identified, and predicting the functional capabilities of microbial communities by PICRUSt showed that microbial genes related to the metabolism of aromatic amino acids (phenylalanine, tyrosine, and tryptophan) were differentially enriched among the control and different CKD stages.
Conclusion
Our results provide solid human evidence of the impact of gut-metabolite-kidney axis on the severity of CKD and highlight a usefulness of specific gut microorganisms as possible biomarker or therapeutic target of this global health burden.
Funding
- Other NIH Support