SuO004GUT MICROBIOTA COMPOSITION AND FRAILTY IN ELDERLY PATIENTS WITH CHRONIC KIDNEY DISEASE

Abstract

INTRODUCTION AND AIMS: Gut microbiota (gMB) has been suggested to contribute to many inflammatory and metabolic disorders typical of the elderly, thus worsening their frailty. A series of alterations of gMB composition and functions have been described also in chronic kidney disease (CKD). Frailty characterizes many CKD elderly patients and is associated with poor clinical outcomes. The aim of our study was to assess gMB composition in CKD elderly patients compared to a group of elderly subjects with normal renal function and to evaluate if changes in gMB might contribute to frailty in CKD. METHOD(S): We studied 64 CKD patients (stage 3b-4, eGFR 15-45 ml/min), categorized as frail (F) and not frail (NF) according to Fried's frailty phenotype score (FFP), and 15 not-frail control subjects with a normal renal function (C). All the subjects included in the study were older than 65. In all CKD patients and controls, we assessed serum C-reactive protein (CRP), blood neutrophil/lymphocyte ratio (L/N), Malnutrition-inflammation-Score (MIS), and gMB composition studied by three methods: semi-quantitative (DGGE), high-throughput sequencing (16S ribosomal RNA), and quantitative real-time PCR (qPCR). RESULT(S): In the whole CKD cohort, the prevalence of frailty defined in accordance to FFP scale was 59%( 38 F and 26 NF). No significant differences in mean age (81,865,8 years in F and 79,0366,6 years in NF), BMI (28,7765,4 in F and 27,763,4 in NF), eGFR (25,6869,7 in F and 26,2613,3 in NF), CRP (0,3760,6 in F and 0,2660,24 in NF), N/L (2,5361 in F and 2.5161 in NF) and prevalence of diabetes (63% in F and 50% in NF) were found between F and NF. Conversely, MIS was significantly higher in F than in NF (7.6+/-5.4 vs 3.961.9, p<0.001). DGGE analysis revealed no significant difference in gMB biodiversity between CKD patients and C as well as between F and NF CKD patients. However, metagenomic analysis showed that CKD patients had higher relative abundance of some potentially noxius bacteria (Citrobacter, Coprobacillus, Anaerotruncus, Ruminococcus torques) and a reduced amount of saccharolytic and butyrate producing bacteria (Prevotella, Faecalibacterium prausnitzii, Roseburia) respect to Controls. Furthermore, in the whole CKD cohort the abundance of some bacteria (unclassified Mogibacteriaceae, Oscillospira) was directly proportional to inflammatory indices (CRP, MIS, N/L), while the abundance of others (Akkermansia, Ruminococcus, Eubacterium) was inversely proportional. Statistically significant differences were also found in bacterial abundance between F and NF CKD patients, with an increase of some genera (Mogibacteriacee, Coriobacteriacee, Eggerthella, Erwinia, Coprobacillus, Anaerotruncus, etc) in F patients. Many of these bacteria have been described as more abundant in other not-CKD frail individuals. CONCLUSION(S): These preliminary results suggest that in CKD gut dysbiosis is associated to inflammation and frailty.