SP345GUT MICROBIOME AND CLINICAL RISK FACTORS IN MAINTENANCE HEMODIALYSIS PATIENTS

Abstract

Introduction and Aims: The gut microbiota (GM) is important for human health and has been implicated in the pathogenesis of many chronic diseases. However, little is known about the composition and effects of the GM in patients undergoing maintenance hemodialysis (MHD). The aim of this study was to examine the GM structure and its association with clinical risk factors in MHD patients. Method(s): In this cross-sectional study, ten MHD patients (7M, 50 +/- 4years, 80% African American) were assessed on a non-dialysis day. Assessment included: bone and body composition by DEXA; arterial function by applanation tonometry; and dietary intake through dietary recalls over the 48h prior to the fecal sample collection. Participants were asked to collect one fecal sample; DNA was extracted and the V4 hypervariable region of the bacterial 16S rRNA gene was sequenced using Illumina MiSeq. Sequence data was analyzed using QIIME 1.9.1. Descriptive statistics were reported while Spearman correlations were used to compare GM operational taxonomic units (representative of >=1% of total bacterial population) and clinical risk factors. Result(s): Taxonomic summary of the GM revealed Firmicutes-to-Bacteroidetes ratio of 1.40+/-0.37, which was positively associated with resting brachial and aortic systolic blood pressures (rho= 0.648 and 0.636, respectively; p<0.05). Additionally, it was positively associated with total and saturated fat consumed on non-dialysis days (rho=0.667 and 0.636, respectively; p<0.05). At the genus level, Bacteroides was the most abundant genus in all patients, ranging from 26.91% to 43.22% (33.59+/-5.71%) of total sequences. Meanwhile, Faecalibacterium was variably represented between patients (median 7.54%; range 0.1 to 23.17% of the total sequences) and was positively associated with total carbohydrate intake (rho=0.636; p<0.05) and negatively associated with carotid-femoral pulse wave velocity (rho=-0.867, p=0.001), a surrogate of arterial stiffness. Concurrently, Akkermansia was not present in four participants and its concentration ranged from 0.01 to 12.02% of sequences (median 0.008%). Furthermore, Prevotella was only present in one participant, but was not associated with any variable. Finally, bacteria genera that have been associated with negative physiological effects were expressed in various concentrations: Desulfovibrio (n=2, 1.41-1.51%) and Bilophila (n=6, 0.01-0.75%), but no associations with any clinical risk factors were observed. Conclusion(s): Similar to other metabolic diseases, the GM showed a high Firmicutes-to-Bacteroidetes ratio at the phyla level. However, at the genus level there was high variability across individuals with some bacteria associated with positive health outcomes. Akkermansia, a gram-negative bacteria that preferentially colonizes the mucus layer and is associated with improved metabolic health, was expressed in low concentrations and was not present in some individuals, similar to Prevotella, which previously has been associated with higher dietary fiber intake. This association, however, was not found because it was present in only one individual. In addition, dietary fiber intake was less than 50% of the recommendation (6.26+/-2.48g/1000kcal). Finally, Faecalibacterium, which contains the machinery for the production of butyrate, was strongly associated with lower arterial stiffness, which is an independent risk factor for cardiovascular (CV) mortality in this population. Further studies should aim to explore the relationship between the GM and CV health in MHD patients.