Progressive Decreased Gut Microbial Diversity in Chronic Kidney Disease

Abstract

Introduction: The human gut microbiota plays a number of important roles in human health and is also implicated in kidney disease. Our aim was to investigate whether the composition of gut microbiota alters during the progression of chronic kidney disease (CKD) and to elucidate a possible relationship between gut microbiota profiles and systemic inflammation in CKD. Methods: A case-control study was carried out in 92 patients with CKD and 96 healthy controls. Fecal microbial communities were profiled with high-throughput sequencing and quantitative real-time polymerase chain reaction. Results: PCoA-based on the UniFrac metric revealed a clear separation of healthy volunteers and CKD patients. The difference between healthy controls and end-stage renal disease (ESRD) patients was much more significant than that between healthy controls and non-ESRD patients. The fecal microbiota was dominated by the phyla Bacteroidetes, Firmicutes, and Proteobacteria in either CKD patients or healthy controls. Compared to non-ESRD patients, 4 groups in Bacteroidetes (Prevotellaceae, Prevotella, Paraprevotella, and Butyricimonas), 9 groups in Firmicutes (Ruminococcaceae, Dialister, Clostridiaceae, Catenibacterium, Roseburia, Ruminococcus, Eubacterium, Coprococcus, and Dorea) and 1 genus in Actinobacteria (Collinsella) were enriched in healthy individuals. Compared to ESRD patients, 3 groups in Bacteroidetes (Prevotellaceae, Prevotella, and Hallella), 8 groups in Firmicutes (Roseburia, Faecalibacterium, Dialister, Coprococcus, Dorea, Catenibacterium, Butyricicoccus, and Oribacterium), and 8 groups in Proteobacteria (Pseudomonadaceae, Pseudomonas, Pasteurellales, Pasteurellaceae, Pseudomonadales, Haemophilus, Parasutterella, and Alcallgenaceae) were enriched in healthy individuals. Two groups in Bacteroidetes, Bacteroidaceae (family), and Bacteroides (genus), were enriched in both ESRD and non-ESRD patients, whereas Parebacteroides (genus), belonging to Bacteroidetes, was only enriched in ESRD patients. Notably, the patients exhibited elevated levels of C-reactive protein, lipopolysaccharide, and serum bacterial DNA. These changes were more significant in ESRD patients than non-ESRD patients. Conclusion: This study is the first report to characterize fecal microbiota in a large sample of patients with different stages of CKD in Chinese population. Progressive decreased gut microbial diversity was observed as kidney function deteriorated. These alterations were associated with impaired intestinal barrier status and increased inflammation. Modifying this ecosystem afford promising therapy for controlling the CKD development.