Decrease in Escherichia-Shigella in the gut microbiota of ESKD patients undergoing maintenance hemodialysis

Abstract

Background: Gut dysbiosis is thought to be involved in the pathogenesis and progression of chronic kidney disease and end-stage kidney disease (ESKD). However, differences in the composition and function of gut microbiota in hemodialysis patients are not consistently concluded.

Methods: A total of 20 patients receiving maintenance hemodialysis (MHD) treatment at the Blood Purification Center of Bethune International Peace Hospital from March 2021 to December 2022 were included based on the inclusion criteria. Additionally, 20 healthy volunteers matched for age, gender, and body mass index were recruited from the Health Examination Center as the healthy control (HC) group. The structure of the gut microbiota community in the study subjects was analyzed using second-generation high-throughput sequencing technology based on 16S rRNA and amplicon sequence variants (ASV) analysis.

Results: There were significant differences in gut microbial communities between the two groups. At the genus level, significant differences were found in 19 genera. Among them, Escherichia-Shigella, Lachnospira, Parasutterella, [Ruminococcus]-torques-group, Butyricicoccus, and Streptococcus were significantly decreased, while Phascolarctobacterium, Ruminococcaceae-UBA1819, Erysipelotrichaceae-UCG-003, Flavonifractor, and Erysipelatoclostridium were significantly increased in MHD patients. In particular, the abnormal decrease in the abundance of p-Proteobacteria.c-Gammaproteobacteria.o-Enterobacterales.f-Enterobacteriaceae.g-Escherichia-Shigella might be a significant characteristic of gut microbiota in MHD patients.

Conclusion: The decreased abundance of Escherichia-Shigella is a signature gut microbiota alteration in patients with ESKD undergoing MHD, and Escherichia-Shigella may represent a key bacterial group warranting exploration in the field of hemodialysis. The dysbiosis of gut microbiota holds promise as a therapeutic target and biomarker for the diagnosis and treatment of MHD.

Keywords: Chronic kidney disease; End-stage kidney disease; Escherichia-Shigella; Gut microbiota; Maintenance hemodialysis.

Fig. 1

Quality of sequencing data and diversity of gut microbiota in MHD patients. (A) Raresome curve showed the number of ASVs in each sample under different sequencing volumes. (B) Venn diagram showing overlapping ASVs between the two groups, 87 of which were specific to MHD. (C) Comparison of Shannon index between the two groups. (D) Comparison of ACE index of intestinal flora between the two groups. (E) Adonis analysis based on Jaccard binary distance. (F) ANOSIM analysis based on Jaccard binary distance

Fig. 2

Composition and comparison of gut microbiota between MHD and HCs. Gut microbiota composition of MHD and HC at phylum (A and B) and genus (C) levels. (D) There were significant differences in microbial communities between the two groups at the genus level. P values were calculated by the Wilcoxon rank sum test, * P < 0.05, ** P < 0.01

Fig. 3

LEfSe analysis based on ASVs characteristics of gut microbiota. (A) Histograms of the LDA scores calculated for the selected taxa show significant differences in microbial types and abundance between MHD(red) and HC(blue). (B) LEfSe dendrogram showing the phylogenetic distribution and developmental characteristics of gut microbiota. Red nodes indicate taxa enriched in MHD compared to HC, and blue nodes indicate taxa enriched in HC compared to MHD. p, phylum; c, class; o, order; f, family; g, genus

Fig. 4

Prediction of differential functional and metabolic alterations of gut microbiota in MHD patients by PICRUSt2 analysis. Selected KEGG pathways were calculated using LDA score histograms displayed

Fig. 5

Spearman rank correlation test was used to analyze the correlation between different ASVs and clinical characteristics in MHD patients. Positive values (red) indicate a positive correlation and negative values (blue) indicate a negative correlation. Solid lines indicate P ≤ 0.01, and dashed lines indicate 0.01 ≤ P ≤ 0.05

Fig. 6

Association between gut microbiota and complications in MHD. (A) Histogram of LDA scores calculated for selected taxa showed significant differences in microbe type and abundance between AY(red) and AN(blue). LDA scores on a log10 scale are indicated at the bottom. The default criteria was LDA > 2.5 and p < 0.05. (B) LEfSe dendrogram showing the phylogenetic distribution and developmental characteristics of gut microbiota. (C) Histogram of LDA scores calculated for selected taxa showed significant differences in microbe type and abundance between TY (red) and TN (blue). LDA scores on a log10 scale are indicated at the bottom. The default criteria was LDA > 3.0 and P < 0.05. (B, D) LEfSe dendrogram showing the phylogenetic distribution and developmental characteristics of gut microbiota. AY, patients with anemia. AN, patient without anemic. TY, patients with hypertension. TN, patient without hypertension. p, phylum; c, class; o, order; f, family; g, genus