Specific gut microbiome and metabolome changes in patients with continuous ambulatory peritoneal dialysis and comparison between patients with different dialysis vintages.

Abstract

In recent years, the role of gut microbiota and derived metabolites in renal disease has attracted more attention. It has been established that the gut microbiota is a potential target for medical interventions in renal disease including chronic kidney disease (CKD), acute kidney injury (AKI) and renal calculus. Emerging evidence has related dialysis treatment to the microbial composition and function of the intestines, and there are many reports related to HD, but few studies have been related to PD. Previous studies have found that PD patients have intestinal flora disturbances, so we speculate that intestinal flora and its metabolites may be the regulatory factors in long-term therapy of PD. And as far as we know, there have been no studies characterized the gut microbiota in PD patients of different dialysis vintages. It is a cross-sectional study based on clinical data and biological samples of 72 patients with CAPD, 13 patients with ESRD and 13 healthy volunteers. The intestinal microecological characteristics of CAPD patients were comprehensively evaluated by combining the intestinal microflora structure, enterotoxin and receptor (serum LPS and LBP), intestinal barrier function index (serum D-Lactate), intestinal uremic toxin (serum IS, PCS, TMAO), fecal SCFAs and other multi-dimensional and multi-omics studies. Furthermore, the changes of intestinal microecology in CAPD patients of different dialysis vintages (≥ 3 and < 12 months, ≥ 12 and < 24 months, ≥ 24 and < 60 months, ≥ 60 months) were further explored, and the correlations between intestinal microecology indicators and some clinical indicators were analyzed. Fecal and serum samples were collected from PD patients (PD group, n = 72), ESRD patients (ESRD group, n = 13) and healthy volunteers (Normal group, n = 13). Fecal samples were subjected to microbiome (16S rDNA) and SCFA (GC-MS) analyses. Serum samples were subjected to LPS, LBP, D-lactate, IS, PCS, and TMAO (ELISA) analyses. The diversity and richness of intestinal flora in CAPD patients were lower than those in healthy people and ESRD patients, and the microflora structure was different. Anaerobes of Blautia and facultative anaerobes and aerobic bacteria with Bacilli and Lactobacillales those in Firmicutes are the main intestinal flora in CAPD patients. The abundance of Bacteroidaceae, Bacteroides, Faecalibacterium and other dominant bacteria in the intestinal tract of CAPD patients decreased. Proteobacteria, Enterobacteriaceae and Escherichia-Shigella increased their colonization (LDA > 4). In CAPD patients of different dialysis vintages, there was no significant change in the diversity and richness of microflora, and the microflora structure of PDC group was significantly different from that of PDD, which the abnormal expansion of enterobacter group was more prominent in PDC and the abundance of Bacteroides group was relatively higher in PDD. Intestinal barrier damage, intestinal uremic toxin accumulation and short-chain fatty acid reduction were observed in CAPD patients, such as the serum level of D-Lactate, PCS and TMAO were significantly higher than that in the Normal group (P < 0.05),and the fecal levels of BA and CA were significantly lower (P < 0.05). The intestinal microecological disorder of PDC group, while that of PDD group showed a better trend. Such as the PDC group had a significantly higher serum level of LPS, D-Lactate and TMAO (P < 0.01), and significantly lower serum level of LBP (P < 0.01), and lower fecal levels of AA and BA (P > 0.05) than the PDD group. The intestinal microecology and metabolic system of CAPD patients had changes compared with healthy people and ESRD non-dialysis patients, and there were differences in CAPD patients with different dialysis vintages. PD patients on dialysis for more than 60 months showed a better trend in the intestinal microecology than patients with 24∼36 months, which suggested that the intestinal microecology of PD patients had a certain ability of self-regulation and remodeling under the management of standardized system and it is necessary to strengthen the monitoring of the intestinal status and the occurrence of related complications in PD patients on dialysis of 24∼36 months of dialysis vintage. It is initially considered that the mechanism of intestinal microecology is a potential target for intervention in the diagnosis and treatment of CAPD and incorporating intestinal microecosystem monitoring into the long-term management of CAPD patients is a new strategy.