Gut dysbiosis and mortality in hemodialysis patients

Abstract

Little is known about the relationship between gut dysbiosis, inflammation, and adverse outcomes in patients with chronic kidney disease. We examined the association of microbial diversity with all-cause mortality in hemodialysis patients. The gut microbiota was assessed by 16S ribosomal RNA gene sequencing. During a median follow-up of 2.1 years, the adjusted risk of death among patients with higher diversity (above median) was 74% lower than that among patients with lower diversity (below median). We then compared the microbial composition between nonsurvivors and survivors in a matched case-control study. We observed significantly lower microbial diversity and higher proinflammatory cytokines among nonsurvivors than survivors. Specifically, the relative abundance of Succinivibrio and Anaerostipes, two short-chain fatty acid-producing bacteria, was markedly reduced in nonsurvivors. Thus, a unique gut microbial composition is associated with an increased risk of mortality among hemodialysis patients and may be used to identify subjects with a poor prognosis.

Fig. 1. Factors associated with the Simpson index.

Univariate analysis of the correlation of the Simpson index with a BMI, b SGA score, c PASE score, d IL-6, and e TNF-α. Natural logarithmic transformation of IL-6 and TNF-α was used to normalize the distributions for univariate analyses. BMI body mass index, IL-6 interleukin-6, PASE the Physical Activity Scale for the Elderly, SGA subjective global assessment, TNF-α tumor necrosis factor-α.

Fig. 2. Kaplan–Meier analysis curves.

Hemodialysis patients were stratified by the median of the Simpson index to assess the unadjusted risks for all-cause mortality.

Fig. 3. Comparison of different metrics of α-diversity between nonsurvivors and survivors after matching.

a Simpson index, b Shannon index. P values were obtained using the Mann–Whitney U test.

Fig. 4. Cladogram showing differentially abundant taxa of the gut microbiota.

a Differential taxon features at the genus level identified by LEfSe according to nonsurvivors and survivors after matching (LDA score >2). b Red and green bars represent taxon features with significantly higher expression in nonsurvivors and survivors, respectively. LDA linear discriminant analysis, LEfSe linear discriminant analysis effect size.

Fig. 5. Relative abundance of the gut microbiota at the genus level between nonsurvivors and survivors after matching.

Parabacteroides, Succinivibrio, and Anaerostipes were enriched in survivors compared with nonsurvivors. P < 0.05 using the Mann–Whitney U test.