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Dryad

Gut dysbiosis and mortality in hemodialysis patients

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Jan 14, 2021 version files 4.32 MB

Abstract

Gut dysbiosis, characterized by decreased microbial diversity, promotes inflammation. Persistent inflammation plays a pathogenic role in complications of chronic kidney disease (CKD). However, little is known about the relationship between gut dysbiosis and adverse outcomes in patients with CKD. First, we examined the association of microbial diversity with all-cause mortality in CKD patients receiving hemodialysis (n=109). The microbial composition of fecal samples was profiled by means of 16S ribosomal RNA gene sequencing. Microbial diversity was calculated using the Simpson index. Participants were stratified into higher- (above the median) and lower-diversity (below the median) groups and were followed up for a median of 2.1 years. Kaplan-Meier analyses revealed a significant association between higher diversity and a lower risk of death (log-rank P=0.015). After adjustment for patient characteristics and comorbid conditions, the risk of death among patients with higher diversity was 74% lower than that among patients with lower diversity (hazard ratio, 0.26; 95% CI, 0.07 to 0.95). Next, in a matched case-control study, we compared the microbial composition between nonsurvivors and survivors who were matched 1:4 for age and sex. We observed significantly lower values of microbial diversity and higher levels of proinflammatory cytokines among nonsurvivors (n=14) than survivors (n=56). Specifically, the relative abundance of Succinivibrio and Anaerostipes, two short-chain fatty acid-producing bacteria, was markedly reduced in nonsurvivors compared with survivors. In conclusion, 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.